UNIVERSIDADE FEDERAL DE MINAS GERAIS  

Escola de Educação Física, Fisioterapia e Terapia Ocupacional  

Programa de Pós-graduação em Ciências do Esporte  

 

 

 

 

 

 

Marcelo Teixeira de Andrade 

 

 

 

 

 

 

DETERMINANTES DA HIPERTERMIA DURANTE O EXERCÍCIO FÍSICO 

EXTENUANTE: uma abordagem translacional 

 

 

 

 

 

 

 

 

 

 

 

 

 
 

Belo Horizonte 
2022 



 
 

Marcelo Teixeira de Andrade 

 

 

 

 

 

 

 

DETERMINANTES DA HIPERTERMIA DURANTE O EXERCÍCIO FÍSICO 

EXTENUANTE: uma abordagem translacional 

 

 
 
 
 

Tese apresentada ao Programa de Pós-Graduação em 
Ciências do Esporte da Escola de Educação Física, 
Fisioterapia e Terapia Ocupacional da Universidade 
Federal de Minas Gerais, como requisito parcial para 
obtenção do título de Doutor em Ciências do Esporte. 

                                                                   
Orientador: Prof. Dr. Samuel Penna Wanner 

 
 
 
 
 
 
 

 
 
 
 
 
 

 
Belo Horizonte 

2022 



 
 

 
 

 
  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A554d 
2022 

 
 
 
 
 
 
 
 
 

 
Andrade, Marcelo Teixeira de 
      Determinantes da hipertermia durante o exercício físico extenuante: uma 
abordagem translacional. [manuscrito] / Marcelo Teixeira de Andrade – 2022. 
      193 f.: il. 
 
      Orientadora: Samuel Penna Wanner 
 
   

Tese (doutorado) – Universidade Federal de Minas Gerais, Escola de Educação 
Física, Fisioterapia e Terapia Ocupacional. 

Bibliografia: f. 187-193 
 
    1. Exercícios físicos – Aspectos fisiológicos – Teses. 2. Regulação corporal – 
Teses.  3. Temperatura – Efeito fisiológico – Teses. 4. Fadiga – Teses. I. Wanner, 
Samuel Penna. II. Universidade Federal de Minas Gerais. Escola de Educação 
Física, Fisioterapia e Terapia Ocupacional. III. Título. 
 

CDU: 612:796 
Ficha catalográfica elaborada pela bibliotecária Sheila Margareth Teixeira Adão, CRB 6: n° 2106, da  
Biblioteca da Escola de Educação Física, Fisioterapia e Terapia Ocupacional da UFMG. 



 
 

 
 

 



 
 

 
 

 

 
 
 
 
 
 
 
 
 
 
 

 

 

 

 

 

 

 

 
 

 

 

 

 

 

 

 

 

 

Este trabalho foi realizado no Laboratório de Fisiologia do Exercício (LAFISE) da 
Escola de Educação Física, Fisioterapia e Terapia Ocupacional (EEFFTO) da 
Universidade Federal de Minas Gerais (UFMG), com os auxílios concedidos pela 
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), pela 
Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) e pelo 
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). 



 
 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
À minha mãe in memoriam. 



 
 

AGRADECIMENTOS 
 

Aos meus pais, Mário e Benvinda in memoriam, pelo apoio em todos os momentos da minha 
vida. Muito obrigado pela educação, dedicação, investimentos e toda confiança depositada em 
mim. Aos meus irmãos Mário Lúcio, Marcos e Mara, e toda à minha família por todo o apoio.  
   
À minha companheira, amiga e namorada, Maryanne. Muito obrigado, pela paciência, pela 
compreensão, por tudo! Muito obrigado, minha linda! Te amo, Mary!    
 
Aos Doutores e/ou Mestres formados pelo LAFISE, Myla Bittencourt, Kássya Regina, 
Roberto Carlos, Pedro  Henrique, Ana Cançado, Pedro Victor (Careca), Francisco 
Coelho (Chico), Cletiana Gonçalves, Nícolas Henrique, William Coutinho, Alexandre 
Sérvulo (Alex), Lucas Drummond, Matheus Mascarenhas (Sacchetto), Carlos Henrique, João 
Paulo, e Rúbio Sabino (Rubão), primeiramente pela amizade, mas também por terem, 
gentilmente, me autorizado a utilizar os dados coletados por vocês. Sem vocês este projeto 
não seria possível. Contém sempre comigo! Tenho uma dívida enorme com cada um de 
vocês!       
   
Ao Nícolas Henrique e à Karina Goulart, pela parceria e colaboração neste projeto. Vocês me 
ajudaram muito! O meu muito obrigado!    
 
À minha orientadora durante o Mestrado e início do Doutorado, Profª. Drª. Danusa Dias 
Soares, por ter aceitado me orientar no Mestrado, pelo carinho, pela compreensão, pela 
paciência – e como teve! –, e pelas críticas que me fizeram crescer muito. Muito obrigado, 
Danusa, e desculpe-me por não ter atendido todas as suas expectativas no início do meu 
Doutorado.  
 
Ao meu querido orientador de Doutorado, Dr. Samuel Penna Wanner, pelo exemplo de 
professor, pesquisador e profissional. Muito obrigado pela oportunidade de trabalharmos 
juntos, pela paciência, pela confiança quando academicamente ninguém mais acreditava em 
mim – e como confiou! -, por todo o carinho e dedicação que você tem comigo e com todos 
os seus alunos. Nós seus alunos somos como irmãos do Lucas Bala e da pequena Laura. 
Muito obrigado por fazer de nós, a cada dia, profissionais melhores! Obrigado por todo o 
apoio durante a realização deste projeto, Samuel!   
 
Ao Prof. Dr. Cândido Celso Coimbra, pela parceria e colaboração neste projeto, utilização do 
Laboratório de Endocrinologia e Metabolismo do Instituto de Ciências Biológicas da UFMG 
por mim e pelos alunos do LAFISE, e por aceitar participar desta banca. Muito obrigado, 
Cândido!    
 
Ao Prof. Dr. Washington Pires, pela parceria e colaboração neste projeto, por sempre estar 
disposto a ajudar os alunos do LAFISE com suas coletas de dados, por sempre compartilhar 
suas experiencias em técnicas cirúrgicas, por ter orientado tantas Monografias de conclusão 



 
 

de curso na EEFFTO com todo carinho e paciência, e por aceitar participar desta banca. Muito 
obrigado, Chitão!    
 
Ao Prof. Dr. Francisco Teixeira Coelho, pela parceria e colaboração neste projeto, por toda 
sua contribuição ao LAFISE, e por aceitar participar desta banca. Muito obrigado, Chico!    
  
Ao Prof. Dr. Dawit Albieiro Pinheiro Gonçalves, pela motivação em melhorar o LAFISE 
ainda mais (“sangue novo”), pela colaboração neste projeto, e por aceitar participar desta 
banca. 
 
Ao Prof. Dr. Luciano Sales Prado, pela parceria e colaboração neste projeto, por toda sua 
contribuição ao LAFISE e por toda sua contribuição na minha formação de professor. Muito 
obrigado, Luciano! 
 
A nossa Técnica de Laboratório do LAFISE, Maira Elisa Cassimiro, pelos ensinamentos de 
biossegurança e procedimentos, tão fundamentais para os nossos experimentos.  
 
Ao Colegiado de Pós-Graduação em Ciências do Esporte, por toda compreensão que tiveram 
durante o período de doença da minha mãe, por terem atendido todas as minhas solicitações, e 
por nunca academicamente terem desistido de mim! Vou ainda contribuir muito com o 
Programa! Faço esse compromisso com vocês! Muito obrigado!  
 
A todos os colegas e professores do LAFISE e da EEFFTO pelo convívio durante todos 

esses anos. 
 
Ao povo brasileiro por custear à minha formação em Mestre e Doutor em uma universidade 
pública.    
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 



 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 

 

 

 

 

 

 

“É muito melhor lançar-se em busca de conquistas grandiosas, mesmo expondo-se ao 

fracasso, do que alinhar-se com os pobres de espírito, que nem gozam muito nem sofrem 

muito, porque vivem numa penumbra cinzenta, onde não conhecem nem vitória, nem 

derrota.” 

 (Theodore Roosevelt) 



 
 

RESUMO 
 

Embora o aumento da temperatura corporal interna (TINT) favoreça respostas fisiológicas 
durante o exercício físico, a hipertermia acentuada está associada à redução do desempenho e 
maior ocorrência de doenças causadas pelo calor. O primeiro objetivo da tese foi revisar 
sistematicamente os estudos que investigaram a TINT de ratos submetidos ao exercício em 
esteira rolante na tentativa de compreender os fatores que influenciam o valor da TINT 
alcançado na fadiga/exaustão. Nesta revisão, foram feitas análises de regressão linear múltipla 
dos dados extraídos dos estudos que utilizaram tanto exercícios com aumentos progressivos 
da velocidade quanto exercícios com velocidade fixa. A revisão sistemática indicou que os 
valores de TINT obtidos na fadiga/exaustão foram explicados principalmente pela temperatura 
ambiente, TINT inicial (pré-exercício) e parâmetros relacionados ao desempenho físico (i.e., 
distância percorrida nos exercícios incrementais e duração nos exercícios constantes). O 
segundo objetivo da tese foi compreender os fatores que influenciam o aumento dos diferentes 
índices (cerebral, abdominal e colônica) de TINT em ratos submetidos ao exercício progressivo 
até a fadiga. Trezentos e setenta registros individuais foram analisados por meio de regressões 
lineares múltiplas hierárquicas, as quais revelaram que a magnitude da hipertermia em ratos 
submetidos à corrida incremental depende principalmente da temperatura ambiente, 
desempenho físico e TINT inicial, independentemente do local de medida da temperatura. 
Esses resultados corroboram os achados da revisão sistemática. O terceiro objetivo da tese foi 
identificar os determinantes do aumento da TINT em indivíduos submetidos a contrarrelógio de 
10 km sob condições de estresse térmico ambiental. Setenta e cinco registros individuais 
foram analisados por meio de regressão linear múltipla hierárquica, a qual mostrou que a 
hipertermia induzida pelo exercício nos corredores depende principalmente da TINT inicial, 
das condições ambientais e da velocidade de corrida. Conclui-se que os principais 
determinantes da hipertermia induzida pelo exercício fatigante são as condições ambientais, 
TINT inicial e parâmetros relacionados ao desempenho físico. Interessantemente, esses 
achados foram semelhantes em ratos e seres humanos, indicando a possibilidade de translação 
de certos resultados entre as duas espécies. 
 
Palavras-chave: Corrida. Fatiga. Hipertermia. Humanos. Ratos. Termorregulação.  

 
 

 

 

 

 

 

 

 

 

 
 



 
 

ABSTRACT 
 
Although the increase in core body temperature (TCORE) favors physiological responses during 
physical exercise, severe hyperthermia is associated with reduced performance and increased 
occurrence of heat illnesses. The first objective of the thesis was to systematically review the 
studies that investigated the TCORE of rats submitted to treadmill exercise to understand the 
factors that influence the TCORE achieved in fatigue/exhaustion. In this review, multiple linear 
regression analyses were performed on data extracted from studies that used both exercises 
with incremental speed increase and exercises with fixed speed. The systematic review 
indicated that the TCORE values obtained in fatigue/exhaustion were mainly explained by 
ambient temperature, initial TCORE (pre-exercise), and parameters related to physical 
performance (i.e., distance covered in incremental exercises and duration in constant 
exercises). The second objective of the thesis was to understand the factors that influence the 
increase of different indices (cerebral, abdominal, and colonic) of TCORE in rats submitted to 
progressive exercise until fatigue. Three hundred and seventy individual records were 
analyzed using hierarchical multiple linear regressions, which revealed that the magnitude of 
hyperthermia in rats submitted to incremental running depends mainly on ambient 
temperature, physical performance, and initial TCORE, regardless of the temperature 
measurement site. These results corroborate the findings of the systematic review. The third 
objective of the thesis was to identify the determinants of the increase in TCORE in individuals 
submitted to a 10 km time trial under conditions of environmental heat stress. Seventy-five 
individual records were analyzed using hierarchical multiple linear regression, which showed 
that exercise-induced hyperthermia in runners depends primarily on initial TCORE, 
environmental conditions, and running speed. We concluded that the main determinants of 
hyperthermia induced by strenuous exercise are environmental conditions, initial TCORE, and 
parameters related to physical performance. Interestingly, these findings were similar in rats 
and humans, indicating the possibility of translating specific results between the two species. 
 
Keywords: Fatigue. Humans. Hyperthermia. Rat. Running. Thermoregulation.  

 

 

 

 

 

 

 

 

 

 

 

 



 
 

LISTA DOS ARTIGOS INCLUÍDOS NA TESE 

 

ESTUDO 1. Core body temperatures of rats subjected to treadmill exercise to fatigue or 
exhaustion: The journal Temperature toolbox 
*Artigo submetido para publicação no periódico Temperature no dia 28 de junho de 2022 
(CiteScore 2020: 7,8; Qualis A3). 
 
ESTUDO 2. Determinants of the core body temperatures at fatigue in rats subjected to 

incremental-speed exercise: The prominent roles played by the ambient temperature, distance 

traveled, initial core temperature, and measurement site 

* Artigo submetido ao periódico International Journal of Biometeorology no dia 12 de 

setembro de 2022 (CiteScore 2020: 5,4: Qualis A2). 

 
ESTUDO 3. Determinants of the core body temperature attained at the end of a 10-km time 

trial under environmental heat stress 

*Artigo em preparação para ser submetido ao periódico Journal of Applied Physiology no 

início de setembro de 2022 (CiteScore 2020: 5,6; Qualis A2). 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 

 

 



 
 

SUMÁRIO 

 
1 INTRODUÇÃO ................................................................................................................... 12 

2 OBJETIVOS ........................................................................................................................ 18 

2.1 Objetivo geral ................................................................................................................. 18 

2.2 Objetivos específicos ...................................................................................................... 19 

3 ESTUDO 1 ............................................................................................................................ 20 

4 ESTUDO 2 .......................................................................................................................... 100 

5 ESTUDO 3 .......................................................................................................................... 151 

6 CONSIDERAÇÕES FINAIS ............................................................................................ 182 

7 CONCLUSÕES .................................................................................................................. 183 

REFERÊNCIAS ................................................................................................................... 184 

 

 

 

 

 



12 
 

 
 

1 INTRODUÇÃO 

 

A termorregulação humana compreende os mecanismos que atuam no controle da 

temperatura corporal interna (TINT) em condições variáveis de cargas térmicas internas (e.g.; 

metabolismo aumentado pelo exercício físico) e externas (e.g.; exposição a ambientes 

diversos) (BLATTEIS; BOULANT; CABANAC; CANNON et al., 2001). Ao longo da 

existência humana na Terra, esses mecanismos termorregulatórios foram fundamentais para 

que a nossa espécie pudesse explorar e se adaptar a diversos ambientes térmicos (GISOLFI; 

MORA; MORA; TERUEL et al., 2000).  

 

Os seres humanos são animais homeotérmicos que possuem a capacidade de manter a TINT em 

uma faixa estreita de variação próxima a 37ºC, independente da temperatura ambiente, 

embora existam oscilações fisiológicas da TINT dentro dessa faixa, conforme fatores 

individuais e ritmos circadianos (ROMANOVSKY, 2018). A TINT é o resultado da relação 

entre o ganho e a perda corporal de energia térmica (por simplicidade, adotaremos o termo 

calor). O controle preciso da TINT ocorre por meio de alças termorregulatórias independentes, 

as quais possibilitam o recrutamento ou inibição de efetores fisiológicos e comportamentais 

que modificam as taxas de produção e perda de calor corporal (ROMANOVSKY, 2018). Se o 

equilíbrio térmico não pode ser alcançado (i.e., produção maior do que a dissipação), o calor é 

armazenado no corpo, levando ao aumento da TINT. Aumentos aproximados de 5 e 6C na 

TINT podem induzir falha do sistema nervoso central (SNC), síndrome da resposta 

inflamatória sistêmica e a eventual morte por falência múltipla dos órgãos (LEON; HELWIG, 

2010).  

 

Desta forma, estudar os mecanismos termorregulatórios envolvidos na capacidade de 

responder e se adaptar aos ambientes extremos e ao exercício físico e, principalmente, aos 

riscos relacionados à combinação desses dois aspectos (i.e., realização de exercícios físicos 

em ambiente quente) é fundamental. Em uma perspectiva mais ampla, os seres humanos estão 

expostos a ambientes extremos que impactam na economia e no trabalho (JAHNKE; 

POSTON; HADDOCK; JITNARIN et al., 2012), nas atividades de lazer e esportivas (EL 

HELOU; TAFFLET; BERTHELOT; TOLAINI et al., 2012; VERNON; RUDDOCK; 

GREGORY, 2021; VIHMA, 2010), e na saúde (ARMSTRONG, LAWRENCE E; CASA, 

DOUGLAS J; MILLARD-STAFFORD, MINDY; MORAN, DANIEL S et al., 2007; LEON; 



13 
 

 
 

HELWIG, 2010). Deste modo, compreender os efeitos dos ambientes extremos sobre a vida 

no nosso planeta, incluindo os efeitos sobre a capacidade de os seres humanos regularem a 

sua temperatura corporal, pode trazer impactos para a sociedade que ultrapassam a esfera 

científica. Neste contexto, o aquecimento global é considerado um dos principais problemas 

emergentes, sendo que, entre 1970 e 2000, a temperatura média do globo aumentou 

rapidamente em 0,5ºC, particularmente devido à emissão de gases que causam o efeito estufa 

(MCMICHAEL; WOODRUFF; HALES, 2006). O aquecimento global impacta a saúde e a 

sobrevivência de várias espécies, visto que está associado com ondas de calor mais 

duradouras em diversas regiões do planeta (FRICH; ALEXANDER; DELLA-MARTA; 

GLEASON et al., 2002). 

 

O aumento da TINT é uma resposta fisiológica marcante ao exercício físico. Esse aumento 

resulta de um desequilíbrio transitório entre as taxas de produção de calor e a perda de calor 

corporal (WEBB, 1995). Mais especificamente, assim que uma sessão de exercício é iniciada, 

a frequência cardíaca e o consumo de oxigênio começam a aumentar e, em 2-3 min, um novo 

estado estável é alcançado. Por exemplo, o aumento do consumo de oxigênio e o consequente 

aumento da produção metabólica de calor são exponenciais e têm uma constante de tempo de 

aproximadamente 30 s (CERRETELLI; SIKAND; FARHI, 1966; WHIPP; WASSERMAN, 

1972). Em contraste, a perda de calor é lenta após o início do exercício, e sua resposta 

exponencial tem uma constante de tempo de 10 min (WEBB; TROUTMAN JR; ANNIS, 

1970). Portanto, o calor é acumulado no centro do corpo e a TINT aumenta no início do 

exercício. 

 

Em seres humanos, os valores de TINT alcançados durante o exercício dependem da 

intensidade do esforço físico; quanto maior a taxa metabólica, maior o nível em que TINT 

estabiliza (NIELSEN, 1966; SALTIN; HERMANSEN, 1966; SAWKA; LEON; MONTAIN; 

SONNA, 2011). Essa relação é independente de uma faixa ampla de condições ambientais, 

principalmente quando a perda de calor por evaporação pode compensar o aumento da 

produção metabólica de calor (ou seja, estresse térmico compensável) (SAWKA; LEON; 

MONTAIN; SONNA, 2011). No entanto, quando os seres humanos realizam exercícios de 

intensidade moderada a vigorosa sob condições com temperaturas ambientais elevadas, a TINT 

não atingirá um estado estável e aumentará continuamente durante o exercício, ou seja, 

estresse térmico não compensável. Para ilustrar a importância da intensidade do esforço, 



14 
 

 
 

Racinais e colaboradores registraram que as ciclistas que conquistaram medalhas de ouro em 

um contrarrelógio por equipe (ou seja, aquelas que desenvolveram maior potência) sob 

estresse térmico ambiental estavam entre as atletas com hipertermia mais acentuada durante 

esta competição (RACINAIS; MOUSSAY; NICHOLS; TRAVERS et al., 2019). Vale 

mencionar que uma atleta alcançou um valor de TINT igual a 41,5ºC. 

 

É interesse notar que a TINT, medida em diferentes locais do corpo, não é homogênea e 

apresenta diferentes padrões de respostas temporais a estímulos que induzem um estado de 

alerta (KIYATKIN, 2007). Sawka et al.  (SAWKA; LEON; MONTAIN; SONNA, 2011) 

afirmam que não existe uma TINT “verdadeira”, porque essa temperatura varia entre os 

diferentes locais mais profundos do corpo, os quais estão localizados dentro das cavidades 

craniana, torácica e abdominal. Nesse sentido, a temperatura dentro de uma determinada 

região do corpo depende: (a) da taxa metabólica local dos tecidos adjacente, (b) da força e da 

magnitude do fluxo sanguíneo local, e (c) dos gradientes de temperatura entre as regiões 

adjacentes do corpo.  

 

O nosso grupo de pesquisa vem investigando as respostas da TINT, medida em diferentes 

locais do corpo, durante o exercício físico fatigante em ratos (DAMASCENO, W. C.; PIRES, 

W.; LIMA, M. R. M.; LIMA, N. R. V. et al., 2015; DRUMMOND; KUNSTETTER; VAZ; 

CAMPOS et al., 2016; FONSECA; PIRES; LIMA; GUIMARAES et al., 2014). Em um 

desses estudos, Fonseca e colaboradores (FONSECA; PIRES; LIMA; GUIMARAES et al., 

2014), implantaram uma cânula guia no encéfalo e um sensor de temperatura na cavidade 

abdominal dos animais, o que possibilitou realizar medidas simultâneas das temperaturas 

hipotalâmica e abdominal durante o exercício na esteira até a fadiga. Os autores demostraram 

que a temperatura hipotalâmica foi maior do que a temperatura abdominal (TABD) durante 

todo o exercício, inclusive no momento da fadiga. Em um outro estudo do nosso grupo, 

Damasceno et al. (DAMASCENO, W. C.; PIRES, W.; LIMA, M. R.; LIMA, N. R. et al., 

2015) implantaram uma cânula guia no encéfalo e um sensor de temperatura na cavidade 

abdominal dos animais, possibilitando medidas simultâneas das temperaturas talâmica e 

abdominal durante a corrida até a fadiga. O estudo mostrou que a temperatura talâmica e a 

TABD apresentaram valores similares quando os ratos fadigaram, ainda que a temperatura 

talâmica tenha sido maior no início do exercício. Enquanto no estudo conduzido por 

Drummond e colaboradores (DRUMMOND; KUNSTETTER; VAZ; CAMPOS et al., 2016), 



15 
 

 
 

a temperatura encefálica medida no córtex encefálico foi inferior à TABD nos momentos finais 

do exercício, inclusive quando os ratos fatigaram. Diante disso, mais estudos são necessários 

para esclarecer as alterações das temperaturas medidas em diferentes locais da região interna 

do corpo, inclusive em diferentes locais dentro do encéfalo. Ademais, é importante 

compreender os determinantes do aumento dos diferentes índices de TINT durante uma sessão 

de exercício físico. 

 

Como mencionado antes, compreender os determinantes do aumento da TINT durante uma 

sessão de exercício físico é fundamental. Entre esses determinantes, destacam-se as condições 

ambientais. Durante exposição a ambientes extremos, ocorrem ajustes termorregulatórios, 

aumentando ou diminuindo as trocas de calor com o ambiente, com o objetivo de proteger o 

organismo de alterações bruscas e acentuadas na sua temperatura. Esses ajustes 

termorregulatórios dependem do recrutamento e da inibição de mecanismos comportamentais 

e fisiológicos que alteram as trocas de calor entre o corpo e o ambiente por meio de processos 

físicos bem conhecidos: condução, convecção, radiação e evaporação (ROMANOVSKY, 

2018). 

 

Além das condições ambientais e da intensidade do esforço físico, existem outros fatores que 

podem impactar o aumento da TINT induzido pelo exercício, entre os quais estão a capacidade 

de dissipação de calor e a massa corporal dos indivíduos. A redução da hipertermia em 

indivíduos aclimatados ao calor está associada a uma maior capacidade sudorífica, 

aumentando a perda de calor por evaporação (MAGALHÃES; PASSOS; FONSECA; 

OLIVEIRA et al., 2010). Alternativamente, a diferença entre a TINT e a temperatura média da 

pele (TPELE) tem sido indicada como um modulador do desempenho, impactando o nível de 

TINT alcançado durante o exercício (SAWKA; CHEUVRONT; KENEFICK, 2012). Além 

disso, as respostas termorregulatórias também são influenciadas pela massa corporal 

(CRAMER; JAY, 2014), mas aparentemente a TINT inicial não parece afetar a TINT alcançada 

na fadiga, pelo menos em seres humanos submetidos a exercícios de intensidade fixa 

(GONZÁLEZ-ALONSO; TELLER; ANDERSEN; JENSEN et al., 1999; NIELSEN; 

STRANGE; CHRISTENSEN; WARBERG et al., 1997). Essas informações indicam que 

vários fatores podem determinar o nível de hipertermia, mas, até onde sabemos, nenhum 

estudo investigou a influência desses fatores por meio de análise multivariada. 

 



16 
 

 
 

Embora o aumento da TINT favoreça as respostas metabólicas durante o exercício, níveis 

acentuados de hipertermia estão associados à redução do desempenho e até mesmo à 

ocorrência de doenças causadas pelo calor. Em relação ao desempenho físico, a TINT tem 

efeitos diretos e indiretos que limitam a capacidade de se exercitar por períodos prolongados 

(CHEUNG, STEPHEN S; SLEIVERT, GORDON G 2004). Por exemplo, o aumento da TINT, 

possivelmente a temperatura encefálica, altera a atividade eletroencefalográfica (NYBO, 

LARS; NIELSEN, BODIL 2001), aumenta a percepção de esforço (NYBO, LARS; 

NIELSEN, BODIL 2001), 2001) e reduz o impulso central para as contrações musculares 

(MORAES; PAULINELLI-JÚNIOR; TEIXEIRA-COELHO; CANÇADO et al., 2019; 

NYBO, LARS; NIELSEN, BODIL, 2001). Além disso, a hipertermia pode indiretamente 

acelerar a fadiga ao desencadear hiperventilação (SAKURADA; HALES, 1998), que pode 

levar à vasoconstrição e redução do fluxo sanguíneo no cérebro (SAKURADA; HALES, 

1998). No que diz respeito à saúde dos seres humanos, a hipertermia acentuada tem sido 

associada a uma maior incidência de choque hipertérmico, a doença do calor mais grave 

(ARMSTRONG, LAWRENCE E; CASA, DOUGLAS J; MILLARD-STAFFORD, MINDY; 

MORAN, DANIEL S et al., 2007). A inflamação sistêmica decorrente da translocação 

bacteriana no intestino parece desempenhar um papel crucial na fisiopatologia do choque 

hipertérmico (GISOLFI, 2000), e evidências indicam que o nível de hipertermia modula a 

função da barreira intestinal (PALS; CHANG; RYAN; GISOLFI, 1997; PIRES; 

VENEROSO; WANNER; PACHECO et al., 2017; PIRES; WANNER; SOARES; 

COIMBRA, 2018). 

 

Diante das informações supracitadas, identificar quais fatores (por exemplo, condições 

ambientais, desempenho físico e TINT pré-exercício) podem afetar o aumento da TINT (i.e., 

hipertermia) durante uma sessão de exercício físico em ratos e em seres humanos é essencial.  

Assim, três estratégias distintas foram adotadas para se alcançar os objetivos dessa tese. 

Inicialmente, foi realizada uma revisão sistemática dos estudos que investigaram a TINT de 

ratos submetidos ao exercício em esteira rolante até a fadiga ou exaustão. Nesta revisão, 

foram feitas análises de regressão linear múltipla dos dados extraídos de estudos que 

utilizaram tanto exercícios com aumentos progressivos da velocidade quanto exercícios com 

velocidade fixa na tentativa de compreender os fatores que influenciam o valor da TINT 

alcançado na fadiga/exaustão. A segunda estratégia consistiu na organização de 

aproximadamente 370 registros individuais contendo a medida da TINT de ratos submetidos ao 



17 
 

 
 

exercício progressivo até a fadiga. A terceira e última estratégia consistiu na organização de 

75 registros individuais contendo a medida da TINT de seres humanos submetidos a um 

contrarrelógio de 10 km realizado em ambiente quente. Após a organização desses registros, 

foram realizadas regressões lineares múltiplas hierárquicas para compreender os fatores que 

influenciam o aumento da TINT causado pelo exercício. Vale mencionar que os dados 

utilizados nas duas últimas estratégias foram coletados por diversos estudantes que 

desenvolveram projetos de pesquisa no LAFISE nos últimos 10 anos. 

 

Por fim, é importante mencionar que essa tese possui um caráter translacional, pois inclui a 

análise de dados coletados em ratos e seres humanos. Nesse contexto, vale destacar que dados 

coletados em ratos podem ser, com certas limitações, utilizados para compreender a fisiologia 

térmica de seres humanos submetidos ao exercício físico, conforme argumentação 

apresentada nos próximos parágrafos. 

 

Ainda que ratos e seres humanos tenham desenvolvido estratégias distintas para enfrentar os 

desafios ambientais (térmicos), os ajustes induzidos pelo exercício na produção e dissipação 

de calor ocorrem na mesma direção em ambas as espécies. A produção de calor aumenta 

acentuadamente com o início do exercício, enquanto a perda de calor cutânea por convecção 

diminui até atingir um limiar de TINT que desencadeia a vasodilatação da pele. Assim, o 

aumento induzido pelo exercício na taxa de produção de calor é sempre mais rápido que o 

aumento na taxa de perda de calor, elevando a TINT no início do exercício em ambas as 

espécies (WANNER; PRÍMOLA-GOMES; PIRES; GUIMARAES et al., 2015; WEBB, 

1995). As respostas termorregulatórias semelhantes com o início do exercício indicam que o 

conhecimento sobre o controle autonômico da termorregulação e sua modulação do 

desempenho físico pode ser de alguma forma intercambiável entre as duas espécies. 

 

Outros exemplos mostram que as transferências de resultados obtidos em experimentos com 

ratos para seres humanos são possíveis. Os efeitos da bupropiona, um inibidor da recaptação 

de dopamina/noradrenalina, em ratos e seres humanos foram bastante semelhantes; em ambas 

as espécies, a bupropiona estendeu o tempo de corrida até a fadiga e acentuou o aumento da 

TINT induzido pelo exercício (HASEGAWA; PIACENTINI; SARRE; MICHOTTE et al., 

2008; WATSON; HASEGAWA; ROELANDS; PIACENTINI et al., 2005). Outra possível 

transferência é a tolerância aprimorada ao esforço físico, causada por um ambiente frio ideal, 



18 
 

 
 

observada em seres humanos (GALLOWAY; MAUGHAN, 1997) e em ratos (FONSECA; 

PIRES; LIMA; GUIMARAES et al., 2014; MOLKOV; ZARETSKY, 2016). 

 

Todavia, devemos reconhecer que a transferência dos achados nem sempre é possível. Por 

exemplo, embora um estudo tenha relatado melhora no desempenho aeróbico em ratos não 

treinados suplementados com Saccharomyces boulardii (SOARES; WANNER; MORAIS; 

HUDSON et al., 2019), esses achados não foram reproduzidos em seres humanos não 

treinados (HUDSON, 2020). A incapacidade de transferir os resultados experimentais pode 

ser explicada pelas diferenças interespécies na microbiota gastrointestinal, dieta e 

metabolismo, entre outros aspectos. 

 

Em resumo, acreditamos que alguns resultados fornecidos por estudos com ratos podem ser, 

com certas limitações, transferidos para o entendimento da fisiologia dos seres humanos, 

contribuindo para a compreensão do sistema termorregulatório humano e indiretamente para 

entendimento sobre os determinantes do desempenho físico. Dessa forma, os pesquisadores 

que realizam pesquisas translacionais devem ter cautela para identificar quando há uma 

oportunidade real de transferência dos dados de uma espécie para outra e quando não há. 

 

 

2 OBJETIVOS 

 

2.1 Objetivo geral  

 

Compreender os determinantes do aumento da TINT durante o exercício físico fatigante tanto 

em ratos quanto em seres humanos. 

 

Para isso, a tese foi dividida em três estudos, de acordo com os objetivos específicos 

descritos abaixo. 

 

 

 

 

 



19 
 

 
 

2.2 Objetivos específicos  

 

Estudo 1 

 

1) Realizar uma revisão sistemática sobre os estudos que investigaram a TINT, medida no 

momento da fadiga ou exaustão, de ratos submetidos ao exercício físico em esteira rolante. 

 

2) Identificar os determinantes do aumento da TINT, medida no momento da fadiga ou 

exaustão, em ratos submetidos a dois tipos diferentes de exercício físico em esteira rolante: 

velocidade fixa ou com aumentos progressivos da velocidade. 

 

Estudo 2 

 

1) Identificar os determinantes do aumento de diferentes TINT – abdominal, colônica e 

encefálica –, medidas no momento da fadiga, em ratos submetidos a exercício físico com 

aumentos progressivos da velocidade em esteira rolante. 

 

2) Comparar as alterações dos diferentes índices da TINT induzidas por uma sessão de 

exercício físico com aumentos progressivos da velocidade até a fadiga.  

 

Estudo 3 

 

Identificar os determinantes do aumento da TINT em indivíduos submetidos a contrarrelógio 

de 10 km sob condições de estresse térmico ambiental. 

 

 

 

 

 

 

 

 

 



20 
 

 
 

3 ESTUDO 1 

 

Core body temperatures of rats subjected to treadmill exercise to fatigue or exhaustion: The 

journal Temperature toolbox 

 

Marcelo T. Andrade1, Karine N. O. Goulart1, Nicolas H. S. Barbosa1, Danusa D. Soares1, André 

G. P. Andrade2, Dawit A. P. Gonçalves1, Thiago T. Mendes3, Cândido C. Coimbra4, Samuel P. 

Wanner1 

 

1 Exercise Physiology Laboratory, School of Physical Education, Physiotherapy and 

Occupational Therapy, Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brazil. 

2 Biomechanics Laboratory, School of Physical Education, Physiotherapy and Occupational 

Therapy, Universidade Federal de Minas Gerais, Belo Horizonte (MG), Brazil. 

3 Department of Physical Education, Faculty of Education, Universidade Federal da Bahia, 

Salvador (BA), Brazil. 

4 Laboratory of Endocrinology and Metabolism, Institute of Biological Sciences, Universidade 

Federal de Minas Gerais, Belo Horizonte (MG), Brazil. 

 

Corresponding author: 

Samuel Penna Wanner, PhD 

Universidade Federal de Minas Gerais 

Av. Antônio Carlos, 6627. Belo Horizonte (MG), Brazil. Zip code: 31.270-901 

E-mail: samuelwanner@ufmg.br  



21 
 

 
 

Abstract 

This study systematically reviewed the literature reporting the changes in rats’ core body 

temperature (TCORE) induced by either incremental- or constant-speed running to fatigue or 

exhaustion. In addition, multiple linear regression analyses were used to determine the 

factors contributing to the TCORE values attained when exercise was interrupted. Four 

databases (EMBASE, PubMed, SPORTDiscus, and Web of Science) were searched in October 

2021, and this search was updated in August 2022. Seventy-two studies (n = 1,538 rats) were 

included in the systematic review. These studies described heterogeneous experimental 

conditions; for example, the ambient temperature ranged from 5 to 40C. The rats quit 

exercising with TCORE values varying more than 8C among studies, with the lowest and 

highest values corresponding to 34.9C and 43.4C, respectively. Multiple linear regression 

analyses indicated that the ambient temperature (p < 0.001), initial TCORE (p < 0.001), 

distance traveled (p < 0.001; only incremental exercises), and running speed and duration (p 

< 0.001; only constant exercises) contributed significantly to explaining the variance in the 

TCORE at the end of the exercise. In conclusion, rats subjected to treadmill running exhibit 

heterogeneous TCORE when fatigued or exhausted. Moreover, it is not possible to determine 

a narrow range of TCORE associated with exercise cessation in hyperthermic rats. Ambient 

temperature, initial TCORE, and physical performance-related variables are the best predictors 

of the TCORE at fatigue or exhaustion. From a broader perspective, this systematic review 

provides relevant information for selecting appropriate methods in future studies designed 

to investigate exercise thermoregulation in rats. 

 

Keywords: body mass, environment, heat, hyperthermia, performance, physical exercise, 

regression analysis, thermoregulation  



22 
 

 
 

Introduction 

Rats are widely used to study the physiological mechanisms underlying the regulation of 

physical performance, including the thermoregulatory mechanisms [1]. In particular, they 

represent an experimental model for investigating exercise performance and physiology 

when the use of human subjects is neither feasible nor desirable [2]. For example, rats are 

used in studies involving invasive procedures that cannot be carried out in humans for 

ethical reasons [2]. These invasive procedures include brain cannulation [3,4], identification 

of exercise-induced activation of hypothalamic areas [5,6], and surgery for denervating 

peripheral receptors [7,8]. Utilizing rats is also an alternative when studies involve 

addressing physiological parameters in human subjects throughout their lifetimes, which is 

often impractical [2]. From the thermal biology perspective, studies of running rats can, with 

certain limitations (e.g., differences in evaporative heat loss), help understand some features 

of exercise thermoregulation in humans [1]. 

 

Physical exercise increases whole-body metabolic rate due to augmented chemical-to-

mechanical energy transformation in contracting skeletal muscles [9]. In rats, the running-

induced increase in metabolic rate can attain levels 2 to 4 times greater than baseline values 

[10-13], leading to higher heat production. Thus, augmented heat loss to the environment is 

necessary to counterbalance enhanced heat production and avoid exaggerated core body 

hyperthermia [14,15]. Interestingly, the increase in heat production precedes the increase in 

cutaneous heat loss, favoring body heat accumulation and the consequent core body 

temperature (TCORE) rise at the beginning of the exercise [1]. After that, the TCORE level 

attained by the rats will significantly depend on the ambient temperature (TAMB) and 

exercise intensity, duration, and protocol [1, 16-18].  



23 
 

 
 

 

Augmented body temperature – either TCORE or muscular temperature – is associated with 

physiological benefits during exercise, including higher enzymatic activity [19], reduced 

saturation of hemoglobin and myoglobin with O2 molecules [20,21], augmented local blood 

flow [22], and attenuated increase in blood viscosity [23]. Therefore, some level of 

hyperthermia is required to promote adequate metabolic responses to physical exertion 

(e.g., adequate O2 supply to contracting muscles). However, severe hyperthermia influences 

the functioning of many physiological systems (e.g., cardiovascular and gastrointestinal 

systems) [24,25] and is associated with the occurrence of heat-related disorders, including 

heatstroke [26,27].  

 

Alongside undesirable effects on health, severe hyperthermia might also favor the 

occurrence of fatigue or exhaustion during prolonged exercises, thus impairing endurance 

[28-30]. The increase in TCORE, particularly brain temperature, changes the 

electroencephalographic activity, increases perceived exertion and ultimately impairs the 

ability of the central nervous system to stimulate the contraction of skeletal muscles [31,32]. 

Moreover, other indirect effects of augmented TCORE may influence endurance, such as 

reduced cerebral blood flow [33], enhanced cardiovascular strain [34,35], altered thermal 

perception [36], and muscle/systemic inflammation [37].  

 

Considering the impacts of severe hyperthermia on an animal’s physical performance and 

health, we considered it essential to carefully assess the extensive literature reporting the 

changes in TCORE in rats exercised to fatigue or exhaustion. By systematically reviewing this 

literature, we expect to provide relevant insight into the factors (e.g., TAMB, body mass, and 



24 
 

 
 

exercise intensity and duration) that may affect the TCORE value when rats quit exercising on 

a treadmill. Moreover, identifying what factors affect the increase in TCORE during exercise 

will allow the development of more effective strategies to mitigate the hyperthermia-

induced degradation of endurance performance and minimize the incidence of severe heat 

illnesses. 

 

Therefore, we aimed to systematically review the studies that recorded TCORE at fatigue or 

exhaustion in rats subjected to incremental- or constant-speed treadmill running. In 

addition, we analyzed the data extracted from these studies using multiple linear regression 

analysis to understand what factors affect the TCORE attained by the rats when they quit 

exercising.   



25 
 

 
 

Methods 

  

Search strategy 

The present systematic review and meta-analysis followed the Preferred Reporting Items for 

Systematic Reviews and Meta-Analysis (PRISMA) guidelines [38]. The searched databases 

were: PubMed (U.S. National Institutes of Health), Web of Science (Clarivate), EMBASE 

(Elsevier), and SPORTDiscus (EBSCO). The following search terms were combined using 

Boolean operators: (exercise OR running) AND (thermoregulation OR hyperthermia) AND 

(fatigue OR exhaustion) AND rat.  

 

The search was conducted in October 2021, with no date restrictions, and all included 

studies were manuscripts written in English that contained original data. An update search 

was conducted in August 2022. Books and book chapters, theses, dissertations, review 

articles, points of view, essays, editorials, and scientific meeting proceedings were not 

included, though their bibliographic reference lists were consulted during the screening 

process. We also checked the reference list of all selected manuscripts to ensure that our 

search strategy has not missed relevant manuscripts.  

 

The following inclusion criteria were set: a) the study sample should consist of rats; b) the 

intervention should be a running exercise on a treadmill; c) the exercise should have been 

performed until the rats were fatigued or exhausted; d) the study should have measured any 

TCORE index (e.g., abdominal, colonic, or brain temperature), at least when rats were fatigued 

or exhausted.  

  



26 
 

 
 

Methodological considerations 

This systematic review focused on studies involving rats subjected to physical exercise. 

Although rats and humans have developed distinct strategies to address environmental 

challenges (e.g., rats have limited evaporative heat loss compared to humans), the exercise-

induced adjustments in heat production and dissipation occur in the same direction in both 

species. Heat production sharply increases with exercise initiation, whereas the convective 

cutaneous heat loss decreases until the attainment of a threshold TCORE that triggers skin 

vasodilation. Thus, the increase in heat production is always faster than the increase in heat 

loss, raising TCORE at the beginning of the exercise in both species [1,39].  

 

Treadmill running was chosen because this exercise modality allows for the continuous 

measurement of thermoregulatory parameters, such as the TCORE and skin temperature 

(TSKIN) [1], and the precise quantification of external work performed by rats [12,40]. 

Moreover, we focused on the TCORE at fatigue and exhaustion because it usually corresponds 

to the highest value attained during exercise and because this was the most reproducible 

thermoregulatory parameter when rats were subjected to repeated incremental running 

[41]. 

 

The terms “fatigue” and “exhaustion” are often used interchangeably in the literature. 

However, many authors differentiate them by stating that exhaustion is synonymous with 

fatigue but more intense [42]; i.e., exhaustion is considered extreme fatigue [1]. In addition, 

from a medical perspective, fatigue indicates a declining ability to respond to stressors, while 

exhaustion indicates an almost complete inability to respond to stressors [43]. 

 



27 
 

 
 

In experiments with exercising rats, fatigue is usually determined as the moment when the 

animals cannot keep pace with the treadmill [44,45] and/or expose themselves to electrical 

stimulation during a predetermined time, which corresponds to 10 s in our experiments 

[3,46 47]. Using this criterion, we observed that fatigued rats could right themselves when 

placed on their backs. In contrast, exhaustion is usually confirmed by observing that 

exhausted rats lose their righting reflex [48-50]. Nevertheless, different criteria exist for 

defining exhaustion; for instance, in the study performed by Hasegawa et al. [51], 

"exhaustion was considered to have occurred when the rat was unable to keep pace with 

the treadmill and lay flat on, and stayed on the grid positioned at the back of the treadmill 

for a period of 30 s despite gently being pushed with sticks or breathed on". 

 

The TCORE (or deep body temperature) would ideally represent the mean temperature of the 

thermal core [52]. In practice, TCORE is represented by a specified temperature, such as the 

abdominal, arterial blood, brain, colonic, or rectal temperature in rats. Of note, the depth at 

which thermocouples are inserted past the anal sphincter determines whether the rectal or 

colonic temperature is measured. The thermal core corresponds to those inner tissues of the 

body whose temperatures are not altered in their relationship to each other by circulatory 

adjustments and changes in heat dissipation to the environment that affect the thermal shell 

of the body [52]. Brain temperatures have been considered a TCORE index [52], although 

evidence showing the independence of brain temperatures from other indices of TCORE is 

available [53]. Rats’ TCORE can be measured through different methods, including 

thermocouples, thermistors [54], and telemetry sensors [55]. 

 



28 
 

 
 

The thermoregulation of small animal species, including rats, depends largely on 

environmental conditions [56] and, therefore, these conditions are another methodological 

aspect deserving attention. In this sense, it is crucial to introduce the thermoneutral zone 

(TNZ) concept. There are many definitions of the TNZ (for a detailed review, see ref. [57]). 

According to the third Glossary of Terms for Thermal Physiology, the TNZ is defined as “the 

range of ambient temperature at which temperature regulation is achieved only by control 

of sensible heat loss, i.e., without regulatory changes in metabolic heat production or 

evaporative heat loss” [52], and this definition is currently prevalent [57]. Using this 

definition, Romanovsky et al. [58] developed a practical way to determine the TNZ of rats by 

measuring the TSKIN of their principal “heat-loss organ”, the tail, and then calculating the heat 

loss index (HLI). Briefly, the HLI is a ratio of two temperature gradients (TSKIN – TAMB and TCORE 

– TAMB) [59] and varies from 0 (maximal vasoconstriction) to 1 (maximal vasodilation). Within 

the TNZ, tail-skin vasoconstriction constantly changes for tail-skin vasodilation, and, 

consequently, high magnitude changes in tail TSKIN and HLI are observed [58].  

 

When Wistar rats are resting in the treadmill setup at TAMBs below 24C, their tails are 

vasoconstricted [46,60], and the HLI stabilizes at levels below < 0.1 (sub-neutral conditions). 

On the other hand, we observed HLI values ranging from 0.2 to 0.3 in resting rats maintained 

inside the chamber that contained the treadmill belt at a local temperature of 24-26C [61-

63], thus suggesting this TAMB range corresponds to the lower end of the TNZ of rats inside 

the treadmill setup. Moreover, at 30C, the HLI varies largely between 0.2 to 0.4, indicating 

thermoneutral conditions [60]. Finally, at 35C, rats’ tails are fully vasodilated [61,64], with 

HLI values consistently above 0.5 (supra-neutral conditions). Therefore, the TNZ of Wistar 



29 
 

 
 

rats resting inside the treadmill setup is located between 23C and 35C, most likely close to 

30C.  

 

It is noteworthy that exercise-induced TCORE increase is exaggerated at 31-32C, as compared 

to 23-24C [65-67], and no steady-state TCORE is attained while running under these warm 

environmental conditions (i.e., 31-32C). Indeed, no previous study tried to determine a 

range of TAMB at which TCORE regulation in an exercising rat is achieved only by control of 

sensible heat loss. Even when TCORE remained unaltered throughout a running session in the 

cold, rats’ tails were clearly vasoconstricted [46]. Moreover, environmental factors other 

than TAMB may influence the TNZ inside the treadmill chamber, such as the wind speed (e.g., 

whether the equipment has an electrical fan in front of the treadmill belt) or relative 

humidity (e.g., rats increase evaporative heat loss from the respiratory tract in proportion to 

exercise intensity [17]). However, because the wind speed and relative humidity were not 

reported in most experiments we reviewed, the TAMB was the only environmental factor 

included as an independent variable in the regression analyses. 

 

Study selection 

Studies were searched and inserted into the Rayyan web application 

(https://rayyan.qcri.org). The selection was carried out in two stages that involved reading 

the titles/abstracts and full texts. Next, studies were screened for inclusion by three 

researchers (MA, NB, SW), with all cases of disagreement discussed until consensus was 

reached. Finally, inclusion and exclusion decisions were duly labeled in the Rayyan web 

application [68]. 

 



30 
 

 
 

The search process retrieved a total of 329 articles. One hundred and eighty-four of these 

articles were excluded for being duplicates. Then, the title and abstract of the 145 remaining 

articles were read, and 53 were excluded at this stage. Next, 92 articles were selected for full 

reading, with 20 of these articles being excluded at this final stage; the reasons for 

exclusions are presented in Figure 1. In the end, 72 studies published between 1968 and 

2022 were included in the systematic review (Figure 1). 

 

Data Extraction 

After selection, the following information was extracted from each article included in the 

systematic review: author, year of publication, rat strain, sex, body mass, age, exercise 

protocol, TAMB, daytime/period when experiments were carried out, TCORE index measured, 

time to fatigue/exhaustion, distance traveled, initial TCORE, and TCORE at fatigue or exhaustion. 

The treadmill speed was also extracted from the manuscripts involving constant-speed 

exercises. We always extracted the information as provided by the authors, even though 

literature provides different definitions for fatigue and exhaustion and for the site of TCORE 

measurement (e.g., rectal vs. colonic). 

 

The data were mainly extracted from the control trials. We did not use data from rats 

subjected to pharmacological and behavioral interventions (e.g., manipulation of brain 

neurotransmission and sleep deprivation, respectively) or from trained or heat-acclimated 

rats because these conditions affect exercise thermoregulation. For example, aerobic 

training improves thermoregulatory efficiency during treadmill running, as trained rats run 

farther distances to attain a similar TCORE at fatigue compared to untrained rats [67,69]. 

Experiments with fasted rats were included in the systematic review if they were not fasted 



31 
 

 
 

for more than 24 h. As reported earlier, fasting was used to standardize the metabolic and 

hormonal parameters before exercise and minimize their influence on performance [70]. 

Moreover, 24-h fasting did not influence endurance in low-intensity exercise under 

environmental heat stress [71]. 

 

When not available in the text or tables, the temperature and performance data were 

extracted from figures using the WebPlotDigitizer (version 4.5, 

https://automeris.io/WebPlotDigitizer; Pacifica, CA, USA) or were obtained through contact 

with the correspondent authors via electronic message. 

 

The extracted data were divided into two tables: data from constant-speed (Table 1) and 

incremental-speed (Table 2) exercises, both to fatigue/exhaustion. The exercises with at 

least three different speed stages were considered incremental exercises. For example, 

Lubbe et al. [72] subjected the rats to an exercise starting at a speed of 10 m/min for 5 min, 

after which the speed was suddenly increased to 30 m/min; therefore, we considered the 

initial 5 min as a warm-up period and the running at 30 m/min as a constant-speed exercise 

to exhaustion. We separated the data from these two protocols due to the marked 

differences in the evolution of running speed, which impacts the evolution of exercise 

intensity and, ultimately, the mechanisms underpinning fatigue/exhaustion. In this sense, 

metabolic factors are likely more critical for regulating fatigue than thermoregulatory factors 

during an incremental exercise [18]. 

 

Analysis of the Studies’ Quality 



32 
 

 
 

The quality of the articles included in the systematic review was determined using a 

qualitative assessment consisting of 13 questions, with answer categories of “no” and “yes”, 

scoring 0 and 1, respectively. Some questions also had an intermediate answer category (i.e., 

“partial”), corresponding to a score of 0.5. All questions and the assessment criteria are 

described in detail in Supplementary file 1. This quality assessment was elaborated by the 

first (MTA) and the last (SPW) authors and then improved by the other collaborators; it is 

worth noting that some of the current study's authors have extensive experience studying 

exercise thermoregulation and performance in rats. 

 

The Pearson’s correlation coefficient was used to assess the strength of the association 

between the years of publication and the studies’ quality. 

 

Multiple linear regression analysis 

This analysis was performed to understand the contribution of different parameters on the 

TCORE attained by rats at fatigue or exhaustion during treadmill running. Variables related to 

the regression model (adjusted R2 and standard error of the estimate), the regression 

coefficients, and the beta weights are reported in the Results section. It is noteworthy that 

the regression coefficients cannot be used to establish the relative importance of specific 

variables within a regression equation because they are based on different units of 

measurement [73]. Therefore, the standardized regression coefficients (i.e., converted to z-

scores), also called beta weights, were presented to provide the reader with a complete and 

practical interpretation of the observed relationships [73]. The analyses were performed 

using the IBM SPSS Statistics software (version 19.0, International Business Machines 

Corporation, Armonk – NY, USA). The significance level was set at p < 0.05. 



33 
 

 
 

 

The following parameters were evaluated when analyzing the incremental exercises: body 

mass, TAMB, distance traveled, and initial TCORE. When the manuscript reported a range for 

rats’ body mass, the highest value was used in the regression analysis because most studies 

exercised the rats at the end of the experimental design. The model did not include daytime 

and time to fatigue because these parameters directly affect the initial TCORE and distance 

traveled, respectively. In addition, strain, sex, exercise protocol, and TCORE index were not 

included because these are categorical parameters. We performed an additional analysis 

that considered only the most common conditions observed in the systematic review to 

ensure that some categorical parameters (e.g., rat strain and TCORE index) have not 

influenced our results. Therefore, the additional analysis included male Wistar rats with their 

abdominal temperature measured while being subjected to an incremental exercise with an 

initial speed of 10 m/min and increases of 1 m/min every 3 min.  

 

When analyzing the constant-speed exercises, we included treadmill speed and exercise 

duration instead of distance traveled in the multiple linear regression analysis. This is 

because faster treadmill speeds are commonly associated with shorter durations and lower 

distances traveled during constant speed exercises, whereas faster speeds are usually a 

prerequisite to traveling farther distances during incremental exercises. In addition, although 

the rats ran at 18 m/min in 16 studies (please see the Results section), the experimental 

conditions were highly variable between these investigations (e.g., rat strain, treadmill 

incline, and measured TCORE). This heterogeneity precluded us from performing an additional 

analysis with sufficient trials and considering only the most common conditions in the 

studies involving constant-speed exercises.  



34 
 

 
 

Results 

Incremental-speed exercise 

Eighteen studies, including 35 experimental trials, investigated the TCORE of rats subjected to 

incremental exercises until they were fatigued/exhausted (Table 1). Among them, seven 

studies provided data from one experimental trial [18,69,74-78], eight studies from two 

trials [47, 67, 79-84], and one study from three [85], four [41] or five trials [66]. 

 

Data from 324 rats were included in this analysis, with an average of 9 ± 4 (mean ± SD) rats 

per experimental trial. The animals subjected to exercise were Wistar male rats in most 

investigations, except for three studies that used Sprague-Dawley male rats [74,79,83] and 

one study that used lean Zucker female rats [75]. Of note, the latter study [75] was the only 

one investigating the thermoregulatory responses of female rats subjected to an 

incremental exercise to fatigue/exhaustion. The average body mass corresponded to 328 ± 

45 g, but it is not always clear whether these values were recorded on the day rats exercised 

(Table 3). 

 

Concerning the exercise protocol, 12 studies reported incremental treadmill running with an 

initial speed of 10 m/min and 1 m/min increments every 3 min (Supplementary Table 1). 

However, Fonseca et al. [47] and Shang et al. [66] used slightly different protocols. In the 

first manuscript, the initial speed and the increments were the same; however, the speed 

was increased every 2 min [47]. In the second manuscript, the rats were subjected to a 

treadmill running with an initial speed of 13 m/min and 1.3 m/min increments every 3 min 

[66]. Finally, Gollnick & Ianuzzo [74] did not precisely describe the time to exhaustion and 

the duration of the running stages, which corresponded in their experiments to the time 



35 
 

 
 

elapsed until the first and second plateau of TCORE. Therefore, this study was not included in 

the multiple linear regression analysis. 

 

The rats ran on average for 40.8 ± 14.9 min and traveled a distance of 749 ± 344 m. Fruth & 

Gisolfi [79] and Ardévol et al. [75] reported the longest and shortest exercise duration (79.9 

and 9.1 min), respectively. The farthest distance traveled corresponded to 1,842 m and was 

observed by Fruth & Gisolfi [79], whereas rats covered the shortest distance (i.e., 163 m) in 

the study by Morozova et al. [83]. The dry TAMB ranged from 12C [47] to 32C [67,85], with 

the average temperature corresponding to 25.7 ± 4.2C. 

 

The abdominal temperature was the TCORE index in most studies included in this systematic 

review. In contrast, Gollnick & Ianuzzo [74], Fruth & Gisolfi [79], Bittencourt et al. [85], and 

Shang et al. [66] measured the colonic temperature, whereas Ardévol et al. [75] and 

Kunstetter et al. [18] measured, respectively, the aortic and brain cortex temperatures. 

Interestingly, Drummond et al. [82] simultaneously measured the abdominal and brain 

cortex temperatures. The initial temperature (i.e., at the beginning of the exercise) ranged 

from 36.7C [41] to 39.4C [74], with average values of 37.5 ± 0.6C. Finally, the TCORE at 

fatigue or exhaustion corresponded to 40.0 ± 1.2C, being 37.3C [47] and 42.4C [79], the 

lowest and highest temperature values recorded (Figure 2A). 

 

We performed a multiple regression analysis to understand the determinants of TCORE 

attained by rats at fatigue and exhaustion during incremental exercises (n = 34 trials). Three 

of the four parameters included in the analysis contributed significantly to explain the 

variance in the TCORE at fatigue/exhaustion: distance traveled (t = 6.863; p < 0.001), TAMB (t = 



36 
 

 
 

9.401; p < 0.001), and initial temperature (t = 6.192; p < 0.001); the contribution of the body 

mass (t = -1.790; p = 0.083) was close to reach statistical significance. This analysis led to the 

following regression equation, with an adjusted R2 = 0.813 and standard error of the 

estimate = 0.521: 

 

TCORE at fatigue/exhaustion = -4.631 – (0.004  Body mass) +  

 + (0.002  Distance traveled) + (0.198  TAMB) + (1.051  Initial TCORE) 

 

Standardized beta coefficients corresponded to -0.144, 0.540, 0.693, and 0.469 for the body 

mass, distance traveled, TAMB, and initial TCORE, respectively (Figure 3A). These data indicate 

that TAMB and body mass were, respectively, the variables with the best and worst predictive 

values used in the model. Moreover, these beta values mean that TCORE at 

fatigue/exhaustion increases by 0.693 (in standard deviations) when TAMB increases by one 

standard deviation – assuming other variables in the model are held constant. Finally, the 

negative values for the t-value and standardized beta coefficient regarding the body mass 

indicate an inverse association between this parameter and TCORE.   

 

An additional analysis, considering only the 18 trials using the most common conditions 

observed in the systematic review, was conducted to ensure that excluding strain, exercise 

protocol, and TCORE index from the original regression analysis has not influenced our results. 

These most common conditions included measuring abdominal temperature in male Wistar 

rats subjected to an incremental exercise to fatigue (not exhaustion), with an initial speed of 

10 m/min and increases of 1 m/min every 3 min. In this case, the same three parameters 

contributed significantly to explain the variance in the TCORE at fatigue – distance traveled (t = 



37 
 

 
 

5.143; p < 0.001), TAMB (t = 5.762; p < 0.001), and initial TCORE (t = 3.292; p = 0.006) – whereas 

the body mass did not (t = -0.859; p = 0.406). This analysis led to the following regression 

equation, with an adjusted R2 = 0.727 and standard error of the estimate = 0.308: 

 

TCORE at fatigue = 14.064 – (0.002  Body mass) + (0.002  Distance traveled) +  

+ (0.147  TAMB) + (0.572  Initial TCORE)  

 

Standardized beta coefficients corresponded to -0.111, 0.709, 0.808, and 0.484 for the body 

mass, distance traveled, TAMB, and initial TCORE, respectively (Figure 3B). Again, these data 

indicate that TAMB and body mass were, respectively, the variables with the best and worst 

predictive values used in the model. 

 

Constant-speed exercise 

Fifty-seven studies, including 101 experimental trials, investigated the TCORE of rats subjected 

to constant exercise until fatigue or exhaustion (Table 2). Among them, 34 studies provided 

data from one experimental trial [4,6,44,45,62,63,86-113], 13 studies from two trials 

[3,8,51,64,70-72,82,114-118], four studies from three trials [13,18,48,119], three studies 

from four trials [47,120,121], one study from five trials [122], and two studies from six trials 

[46,123]. 

 

Data from 1,214 rats were included in this analysis, with an average of 12 ± 8 (mean ± SD) 

rats per experimental trial. In most investigations, the animals subjected to exercise were 

Wistar and Sprague-Dawley rats, except Moran et al. [99], which used Zabar rats, and 

Francesconi et al. [92], which did not report the strain. Only two studies investigated the 



38 
 

 
 

thermoregulatory responses of female rats subjected to constant exercise [72,116]. The 

average body mass corresponded to 375 ± 83 g (Table 3). 

 

Concerning the exercise protocol, 16 of the 57 studies reported constant treadmill running 

at 18 m/min (Supplementary Table 2). This was the most common protocol found in the 

literature, possibly because 18 m/min corresponds to approximately 65-80% of the 

maximum aerobic speed attained by untrained rats [41,124] and thus allows elevated 

metabolic heat production for long periods. The fastest running speed corresponded to 30 

m/min [72], whereas the slowest speed was 9.14 m/min, used in a series of studies by 

Hubbard’s group in the 1970s and 1980s [48,70,115,122]. 

 

The rats ran on average for 63.7 ± 47.8 min and traveled a distance of 1,037 ± 869 m. Lima et 

al. [6] and Lubbe et al. [72] reported the longest and shortest exercise duration (287.0 and 

5.6 min), respectively. Therefore, the farthest distance traveled corresponded to 4,908 m 

and was observed by Lima et al. [6], whereas rats covered the shortest distance (i.e., 168 m) 

in the study by Lubbe et al. [72]. The dry TAMB ranged from 5C [46] to 40C [99], with the 

average temperature corresponding to 25.4 ± 8.2C. Of note, Caputa & Kamari [116] 

initiated an experimental trial at a TAMB of 45C but gradually decreased it reaching 27C; this 

strategy aimed to maintain hypothalamic temperature around 41C while rats were running. 

 

In most studies included in this systematic review, the rectal and abdominal temperature 

were the TCORE index measured. Seven studies simultaneously recorded the rectal/abdominal 

and brain temperatures in the same rats [47,51,82,109,116,117,119]. The initial pre-exercise 

temperature ranged from 33.5C [72] to 40.4C [116], with average values of 37.6 ± 0.9C. 



39 
 

 
 

Finally, the TCORE at fatigue or exhaustion corresponded to 40.0 ± 1.8C, being 34.9C [46] 

and 43.4C [92], the lowest and highest temperature values recorded (Figure 2B).  

 

Multiple linear regression analysis was done to understand the determinants of TCORE values 

when rats quit running during constant exercises. Four of the five parameters included in the 

analysis contributed significantly to explaining the variance in the TCORE at 

fatigue/exhaustion: running speed (t = -5.610; p < 0.001), time to fatigue or exhaustion (t = 

2.728; p = 0.008), TAMB (t = 10.022; p < 0.001), and initial TCORE (t = 7.756; p < 0.001). In 

contrast, the body mass (t = -0.714; p = 0.477) did not contribute significantly to explaining 

the variance of TCORE. This analysis led to the following regression equation, with an adjusted 

R2 = 0.786 and standard error of the estimate = 0.808: 

 

TCORE at fatigue/exhaustion = -2.627 – (0.001  Body mass) – (0.105  Running speed) + + 

(0.005  Time to fatigue) + (0.120  TAMB) + (1.097  Initial TCORE) 

 

Standardized beta coefficients corresponded to -0.040, -0.294, 0.139, 0.535, and 0.443 for 

the body mass, running speed, time to fatigue/exhaustion, TAMB, and initial TCORE, 

respectively (Figure 4). Again, TAMB and body mass were the variables with the best and 

worst predictive values used in the model. Finally, the negative values for the t-value and 

standardized beta coefficient regarding the body mass and running speed indicate the 

existence of inverse associations between these parameters and TCORE. 

 

 

 



40 
 

 
 

Quality assessment 

The quality assessment of the studies in which rats were subjected to incremental and 

constant-speed exercises is presented in Table 4.  

 

Concerning the studies with incremental exercises, the average score was 10.1 ± 1.1 (mean ± 

SD) in 13.0 maximum possible points. All manuscripts attained the maximum score in the 

questions related to the objective, method for measuring TCORE, and conclusions. In contrast, 

the lowest scores were related to the lack of a limitations paragraph and inadequate 

information on the environmental conditions and daytime when experiments were 

conducted (more details in Supplementary Table 3). Interestingly, the publication date was 

positively associated with the quality score given to a manuscript (R2 = 0.300, p = 0.019; 

Pearson’s coefficient), thus indicating that the more recent studies were evaluated better 

than older ones. 

 

With respect to the studies with constant-speed exercises, their average score was 9.3 ± 1.5 

points (mean ± SD). The highest scores were obtained in the questions regarding the study 

objectives, information on age and body mass, method for measuring TCORE, continuous 

measurement of TCORE during the exercise (i.e., more than two time points), and conclusions. 

In contrast, the lowest scores were related to the lack of a limitations paragraph and 

insufficient information on daytime when experiments were conducted (more details in 

Supplementary Table 4). Again, the publication date was positively associated with the 

quality score given to a manuscript (R2 = 0.426, p < 0.001), thus indicating that the more 

recent manuscripts received better scores than older ones.  



41 
 

 
 

Discussion 

The present systematic review provides extensive information regarding the TCORE attained 

by rats when exercising to fatigue or exhaustion and relevant information on the factors 

modulating the running-induced TCORE increase. The studies mainly investigated exercise 

thermoregulation in male Wistar or Sprague-Dawley rats and described heterogeneous 

experimental conditions; for example, TAMB ranged from 5 to 40C, whereas the initial (pre-

exercise) TCORE ranged from 33.5 to 40.4C. Quite fascinating, TCORE values reported at 

exercise cessation varied approximately 8C among the studies reviewed. The present 

systematic review also revealed that higher TAMB, initial TCORE, and physical performance-

related variables (e.g., exercise duration for constant running or distance traveled for 

incremental running) are associated with higher TCORE at fatigue or exhaustion.  

 

The lowest TCORE value (i.e., 34.9C) at fatigue/exhaustion was observed in rats running in a 

cold environment [46]. Although this value is similar to hypothermic states induced 

experimentally by causing severe aseptic inflammation [125,126], Guimarães et al. [46] did 

not report fatalities following treadmill running, suggesting that hypothermia was reversed 

after the exercise. Interestingly, rats seem to have greater endurance under cold than 

temperate conditions [47,127]. On the other hand, the highest TCORE values were generally 

associated with fatalities. For example, almost every sedentary (i.e., non-trained) rat 

attaining more than 43.0C did not survive [79]. Under these conditions, animal death 

results from heatstroke, a life-treating condition associated with uncontrolled systemic 

inflammatory response syndrome and disseminated intravascular coagulation, which 

combine to induce multi-organ system dysfunction and failure [27,128]. 

 



42 
 

 
 

TAMB was the primary parameter determining the TCORE attained at fatigue or exhaustion 

during incremental and constant exercises, with augmented environmental heat stress 

inducing more significant hyperthermia. This finding confirms previous observations, 

including experiments when different TAMBs were used to induce different levels of 

hyperthermia [46,47,65]. Indeed, the apparent dependence of exercise hyperthermia on 

TAMB reinforces the notion that the regulation of TCORE in small mammals (e.g., rats and 

mice), which have a higher body mass-to-body surface ratio than bigger mammals, is 

susceptible to slight variations in TAMB [56,125,129,130]. Therefore, high TAMB limits the 

ability of rats to dissipate heat through dry pathways (e.g., convection and radiation), thus 

favoring marked increases in TCORE. Interestingly, while running in the cold, the facilitated 

heat exchange with the environment due to the high body mass-to-body surface ratio is not 

compensated by increased metabolism and, therefore, rats become hypothermic [46]. 

 

The initial TCORE also determined its level when exercise was interrupted; the rats starting the 

treadmill running with higher TCORE were the ones that became fatigued or exhausted with 

more severe hyperthermia. Indirectly, this observation confirms the experimental evidence 

showing a circadian influence [80,81] or the influence of prior exposure to stress [84] or hot 

environments [119] on thermoregulation during exercise. The prominent role played by the 

initial TCORE also highlights the importance of developing rigorous designs that control the 

daytime at which experiments are conducted and ensure that rats are tested under stress-

free conditions. 

 

The distance traveled also determined TCORE at fatigue or exhaustion; therefore, the rats that 

ran farther attained higher temperatures during incremental exercise. In the case of this 



43 
 

 
 

protocol, the distance traveled is a performance index that provides information on exercise 

duration but primarily on intensity. As speed gradually increases, the rats will cover longer 

distances within an exact time interval. Interestingly, the prominent role played by the 

exercise intensity in increasing TCORE corroborates with data obtained from athletes. For 

example, the women cyclists winning gold medals in a team time trial (i.e., the ones with the 

highest power output) under environmental heat stress were among the athletes with 

higher hyperthermia levels (up to 41.5C) during this competition [131]. Taken together, our 

current data in rats and data obtained from athletes suggest that the intensity of physical 

exertion determines the hyperthermia level attained during incremental exercise in rats or 

self-paced intermittent exercise in humans. 

 

During constant-speed exercises, the TCORE at exercise interruption was positively associated 

with running duration while negatively associated with treadmill speed. Although a faster 

treadmill speed produces more intense increases in metabolic rate, tolerance to exercise 

under these conditions is very restricted. For example, male rats could run for less than 6 

min at 30 m/min; indeed, this speed is greater than the maximum aerobic speed attained by 

untrained rats reported in some studies included herein [82,111,118]. On the other hand, 

several studies that subjected rats to hyperthermic exhaustion consisted of slow treadmill 

speeds (i.e., 9.14 and 11 m/min) during prolonged periods under environmental heat stress 

[48,114,120]. 

 

Finally, the body mass was the factor analyzed that less predicted the TCORE at fatigue or 

exhaustion, regardless of the exercise protocol. Moreover, the associations between the 

body mass and TCORE level were consistently negative, with lighter rats more susceptive to 



44 
 

 
 

heating up. In this sense, lighter animals will heat up faster than heavier animals, provided 

the same amount of heat is stored in the core body region, mainly if heat originates from 

external sources. In contrast, it is expected that a lower body mass would exert a protective 

thermoregulatory role, as previously shown in humans. For instance, treadmill walking at a 

fixed external workload elicits a lower rate of metabolic heat production in lighter than 

heavier individuals [132]. Therefore, whether the body mass indeed contributes inversely to 

determining the rats’ TCORE at fatigue or exhaustion is an issue to be investigated carefully in 

future studies. Nevertheless, despite the divergent effects observed in rat and human 

experiments, body mass is a concern for interpreting data in weight-bearing exercises. Also, 

caution should be exercised in interpreting thermoregulatory data in rat experiments when 

body mass is different between experimental groups, such as the lower body mass in 

spontaneously hypertensive rats than in normotensive Wistar rats [82] and the reduction in 

body mass caused by aerobic training in rats subjected to a high-fat diet [133]. 

 

This systematic review included 72 articles published between 1968 and 2022. Among these 

studies, only three subjected female rats to treadmill running [72,75,116]. The lack of data 

on female rats reproduces the underrepresentation of women in research dealing with 

exercise thermoregulation. While Hutchins et al. [134] reported that women accounted for 

30% of the human subjects in the exercise thermoregulation research published in 2019, we 

observed that females represented only 2% of the rats investigated since 1968. The 

underrepresentation of women/females is undesirable because it significantly limits the 

generalization ability of the findings obtained only in men/males. This issue must be resolved 

soon, considering the increased number of women involved in physically demanding work 

activities [135] and their growing participation in elite sports [136,137].  



45 
 

 
 

 

The manuscripts included in the present review had their quality assessed as recommended 

by the PRISMA guidelines [38]. Although the average score was higher than 9 in 13 

maximum possible points for the studies involving incremental- or constant-speed exercises, 

some relevant points should be highlighted. First, the authors of the current review 

elaborated themselves the checklist for quality assessment; therefore, some criteria seen as 

necessary by other research groups may have been left aside from the assessment. Second, 

positive and significant correlations were observed between the publication date and quality 

score, indicating that the more recent manuscripts received better scores than older ones. 

This observation is expected because the requirements for scientific publishing have become 

more stringent over time. Indeed, the recent manuscripts have method sections, particularly 

the statistical analysis, which is much more extensive and detailed than the older ones. 

 

Despite the criticisms presented earlier, the quality assessment provided some crucial 

information for enhancing the quality of future experiments on the topic, including the 

necessity of more comprehensive control of methodological issues, such as the daytime 

when experiments were performed and the environmental factors other than TAMB. The 

current findings also encourage inserting the studies’ limitations at the end of the discussion 

section. Furthermore, it is worth noting that while the more recent studies received better 

scores in most criteria (e.g., description/use of familiarization sessions with treadmill 

running), this statement is not valid for all criteria. For example, the description of 

environmental conditions followed the opposite way, suggesting that the authors are not 

controlling these factors (e.g., relative humidity and artificial airflow inside the treadmill) so 

effectively as in the past. Indeed, the airflow generated by electric fans may facilitate 



46 
 

 
 

convective cutaneous heat loss [2], and rats can evaporate water from their respiratory tract 

while running [17]. 

 

The present systematic review is not free of limitations. First, the data used in the multiple 

linear regression analysis consisted of average data extracted from the manuscripts included 

in the review. This is not an ideal procedure because average TCORE may be associated with 

different levels of heterogeneity or result from different sample sizes in the studies we 

reviewed. Ideally, data from individual rats should be used to run the regression analysis; 

however, these data are not available because several manuscripts were published more 

than 30 years ago. Second, data related to cutaneous heat loss and metabolic heat 

production were not extracted from the manuscripts included in the review. Because the 

changes in TCORE result from imbalances between the rates of heat production and 

dissipation [1,39], these aspects should be considered in future investigations.  

 

Third, body mass data were reported as a range in several studies, and we did not have 

access to the body mass measured on the day of the treadmill exercise. In this case, we 

considered the greatest mass, which may have added imprecision to our analysis. Fourth, we 

included data from different TCORE indices, namely the abdominal, brain cortex, and colonic 

temperatures. The temperatures measured in specific body compartments are not 

homogeneous and do not respond in a similar way (particularly regarding their time course) 

to several arousing stimuli [138] and physical exercise [139]. Nonetheless, a sub-analysis 

using only the abdominal temperature measured during incremental exercises reproduced 

most findings of the analysis using the three TCORE indices, thus suggesting that the site of 

TCORE measurement was possibly not a confounding factor in the outcomes of the multiple 



47 
 

 
 

linear regression analyses. Despite all these limitations, essential patterns have emerged 

from regression analyses, consistent with some existing ideas in the literature, as discussed 

earlier. 

 

In conclusion, when fatigued or exhausted, rats subjected to treadmill running exhibit 

heterogeneous TCORE values. Moreover, it is not possible to determine a single TCORE or a 

narrow range of TCORE associated with exercise cessation in hyperthermic rats. More 

importantly, the present systematic review helps to understand the parameters that 

determine the TCORE values attained at fatigue/exhaustion in two physical exercise protocols, 

with a particular reference to TAMB, initial TCORE, and physical performance-related 

parameters (i.e., distance traveled in the incremental exercises and duration in the constant 

exercises). In contrast, among the factors analyzed, the body mass was the one that least 

predicted the level of TCORE attained in both exercise protocols. Finally, from a broader 

perspective, this systematic review provides relevant information for selecting appropriate 

methods in future studies designed to investigate exercise thermoregulation in rats. 



48 
 

 
 

Funding 

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível 

Superior - Brasil (CAPES) - Finance Code 001. NHSB was the recipient of post-graduate 

fellowship from CAPES, whereas KNOG received a post-doctoral fellowship from 

CAPES/Print. SPW receives a fellowship from the Conselho Nacional de Desenvolvimento 

Científico e Tecnologico (CNPq) for being a productive researcher (grant number 

315199/2021–0). DAPG is currently funded by the Fundação de Amparo à Pesquisa do 

Estado de Minas Gerais (FAPEMIG, grant number APQ-01268-21). DDS, DAPG, TTM, and SPW 

are researchers of the MEDIANTAR group, which is supported by 

CNPq/MCTIC/CAPES/FNDCT/PROANTAR (grant number 442645/2018-0).  



49 
 

 
 

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