Validity and reproducibility of the CALERA Research Sensor to estimate core temperature at different intensities of a cycling exercise in the heat.

Recent heatwaves have highlighted the importance of accurate and continuous core temperature (TCORE) monitoring in sports settings. For example, accentuated rises in TCORE caused by physical exercises under environmental heat stress increase the risk of heat illnesses. Thus, using valid and reproducible devices is essential to ensure safe sports practice. In this study, we assessed the validity and reproducibility of the Calera Research Sensor (CRS) in estimating the TCORE of male and female participants during cycling exercise in a hot environment. Seven male (age: 36.2 ± 10.1 years) and eight female cyclists (age: 30.1 ± 5.0 years) underwent two identical cycling trials in a dry-bulb temperature of 32 °C and relative humidity of 60%. The protocol consisted of an initial 10-min rest followed by a 60-min exercise comprising 10 min at 20%, 25 min at 55%, and 25 min at 75% of maximal aerobic power, and an additional 25 min of post-exercise recovery. TCORE was recorded simultaneously every minute using a gastrointestinal capsule (TGi) and the CRS (TSENSOR). Bland-Altman analysis was performed to calculate bias, upper (LCS) and lower (LCI) concordance limits, and the 95% confidence interval (95%CI). The maximum acceptable difference between the two devices was predetermined at ±0.4 °C. A mixed linear model was used to assess the paired differences between the two measurement systems, considering the participants, trials, and environmental conditions as random effects and the cycling stages as fixed effects. An intra-class correlation coefficient (ICC) of 0.98 was recorded when analyzing data from the entire experiment. A non-significant bias value of 0.01 °C, LCS of 0.38 °C, LCI of -0.35 °C, and CI95% of ±0.36 °C were found. When analyzing data according to the participants' sex, CRS reproducibility was high in both sexes: ICC values of 0.98 and 0.99 were reported for males and females, respectively. CI95% was 0.35 °C in experiments with males and 0.37 °C with females, thereby falling within the acceptable margin of difference. Therefore, CRS was considered valid (compared to TGi) and reproducible in estimating TCORE in both sexes at various intensities of cycling exercise in the heat.

Effects of physical training on hypothalamic neuronal activation and expressions of vasopressin and oxytocin in SHR after running until fatigue.

To assess the influence of physical training on neuronal activation and hypothalamic expression of vasopressin and oxytocin in spontaneously hypertensive rats (SHR), untrained and trained normotensive rats and SHR were submitted to running until fatigue while internal body and tail temperatures were recorded. Hypothalamic c-Fos expression was evaluated in thermoregulatory centers such as the median preoptic nucleus (MnPO), medial preoptic nucleus (mPOA), paraventricular nucleus of the hypothalamus (PVN), and supraoptic nucleus (SON). The PVN and the SON were also investigated for vasopressin and oxytocin expressions. Although exercise training improved the workload performed by the animals, it was reduced in SHR and followed by increased internal body temperature due to tail vasodilation deficit. Physical training enhanced c-Fos expression in the MnPO, mPOA, and PVN of both strains, and these responses were attenuated in SHR. Vasopressin immunoreactivity in the PVN was also increased by physical training to a lesser extent in SHR. The already-reduced oxytocin expression in the PVN of SHR was increased in response to physical training. Within the SON, neuronal activation and the expressions of vasopressin and oxytocin were reduced by hypertension and unaffected by physical training. The data indicate that physical training counterbalances in part the negative effect of hypertension on hypothalamic neuronal activation elicited by exercise, as well as on the expression of vasopressin and oxytocin. These hypertension features seem to negatively influence the workload performed by SHR due to the hyperthermia derived from the inability of physical training to improve heat dissipation through skin vasodilation.

Normal gastrointestinal temperature values measured through ingestible capsules technology: a systematic review.

Climate change has amplified the importance of continuous and precise body core temperature (Tcore) monitoring in the everyday life. In this context, assessing Tcore through ingestible capsules technology, i.e., gastrointestinal temperature (Tgastrointestinal), emerges as a good alternative to prevent heat-related illness. Therefore, we conducted a systematic review to point out values of normal Tgastrointestinal measured through ingestible capsules in healthy humans. The study followed PRISMA guidelines and searched the PubMed and Scielo databases from 1971 to 2023. Our search strategy included the descriptors ("gastrointestinal temperature") AND ("measurement"), and eligible studies had to be written in English and measured Tgastrointestinal using ingestible capsules or sensors in healthy adults aged 18-59 at rest. Two pairs of researchers independently reviewed titles and abstracts and identified 35 relevant articles out of 1,088 in the initial search. An average value of 37.13 °C with a standard deviation of 0.24 °C was observed, independently of the gender. The values measured ranged from 36.70 °C to 37.69 °C. In conclusion, this systematic review pointed out the mean value of 37.13 ± 0.24 °C measured by ingestible capsules as reference for resting Tgastrointestinal in healthy adult individuals.

Swimming Training Does Not Affect the Recovery of Femoral Midshaft Structural and Mechanical Properties in Growing Diabetic Rats Treated with Insulin.

BACKGROUND: The effects of swimming training associated with insulin treatment on the cortical bone health in young rats with severe type 1 diabetes remain unclear, although there is evidence of such effects on the cancellous bone. This study examined the effects of swimming training combined with insulin therapy on the femoral midshaft structural and mechanical properties in growing rats with type 1 diabetes. METHODS: Male Wistar rats were divided into six groups (n = 10): control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary plus insulin and diabetic exercise plus insulin. Diabetic rats received an injection (60 mg/kg body weight) of streptozotocin (STZ). Exercised animals underwent a swimming program for eight weeks. RESULTS: Diabetes induced by STZ decreased the bone mineral content (BMC) and density (BMD), and cortical thickness and maximum load and tenacity in the femoral midshaft. Insulin treatment partially counteracted the damages induced by diabetes on BMC, BMD and cortical thickness and tenacity. Swimming training did not affect the femoral structural and mechanical properties in diabetic rats. The combination of treatments did not potentiate the insulin effects. In conclusion, swimming training does not affect the benefits of insulin treatment on the femoral midshaft structural and mechanical properties in growing rats with severe type 1 diabetes.

Impaired thermoregulation in spontaneously hypertensive rats during physical exercise is related to reduced hypothalamic neuronal activation.

This study aimed to evaluate the physical exercise-induced neuronal activation in brain nuclei controlling thermoregulatory responses in hypertensive and normotensive rats. Sixteen-week-old male normotensive Wistar rats (NWRs) and spontaneously hypertensive rats (SHRs) were implanted with an abdominal temperature sensor. After recovery, the animals were subjected to a constant-speed treadmill running (at 60% of the maximum aerobic speed) for 30 min at 25 °C. Core (Tcore) and tail-skin (Tskin) temperatures were measured every minute during exercise. Ninety minutes after the exercise, the rats were euthanized, and their brains were collected to determine the c-Fos protein expression in the following areas that modulate thermoregulatory responses: medial preoptic area (mPOA), paraventricular hypothalamic nucleus (PVN), and supraoptic nucleus (SON). During treadmill running, the SHR group exhibited a greater increase in Tcore and an augmented threshold for cutaneous heat loss relative to the NWR group. In addition, the SHRs showed reduced neuronal activation in the mPOA (< 49.7%) and PVN (< 44.2%), but not in the SON. The lower exercise-induced activation in the mPOA and PVN in hypertensive rats was strongly related to the delayed onset of cutaneous heat loss. We conclude that the enhanced exercise-induced hyperthermia in hypertensive rats can be partially explained by a delayed cutaneous heat loss, which is, in turn, associated with reduced activation of brain areas modulating thermoregulatory responses.

Voluntary running counteracts right ventricular adverse remodeling and myocyte contraction impairment in pulmonary arterial hypertension model.

AIM: Analyze the effects of voluntary running during the development of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) on the right ventricle (RV) structure, RV myocyte contractility and intracellular Ca2+ transient in rats with MCT-induced PAH. MAIN METHODS: Male Wistar rats were housed sedentary or with free access to a running wheel after MCT or saline injection for until HF or median end-point day of HF in sedentary animals (24 days). Echocardiographic examination and exercise tolerance test were carried out at specific time points of the experimental period. After euthanasia, the heart was dissected, weighed and processed for either histological or single myocyte contractility and intracellular Ca2+ transient analyzes. KEY FINDINGS: Voluntary running delayed the onset of HF (29 days) and the increase in pulmonary artery resistance, and improved exercise tolerance. In the median end-point day of HF, exercise retarded RV adverse remodeling (i.e. increase in extracellular matrix and collagen content). At this stage, exercise also delayed impairments in cell contractile function (i.e. amplitude and times to peak and to half relaxation) and intracellular calcium cycling (i.e. amplitude and times to peak and to half decay) in RV single myocytes. SIGNIFICANCE: Along with HF onset delay and physical effort tolerance enhancement, voluntary running during the development of PAH postpones pulmonary artery resistance increases, RV adverse remodeling and myocyte contractility and intracellular calcium cycling deterioration in rats. Therefore, self-paced intermittent exercise of high intensity may contribute positively to the health and survival of individuals with PAH.

Swimming training potentiates the recovery of femoral neck strength in young diabetic rats under insulin therapy.

OBJECTIVE: To test whether swimming training benefits femoral neck strength in young diabetic rats under insulin therapy. METHODS: A total of 60 male Wistar rats (age: 40 days) were divided equally into the following six groups: control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary plus insulin and diabetic exercise plus insulin. Diabetes was induced with a unique intraperitoneal injection (60 mg/kg body weight) of streptozotocin. Seven days after the injection and after 12 hours of fasting, the animals with blood glucose levels ≥300 mg/dL were considered diabetic. Seven days after the induction of diabetes, the animals in the exercise groups were subjected to progressive swimming training (final week: 90 min/day; 5 days/week; 5% load) for eight weeks. The animals in the insulin groups received a daily dose of insulin (2-4 U/day) for the same period. RESULTS: Severe streptozotocin-induced diabetes reduced the structural properties of the femoral neck (trabecular bone volume, trabecular thickness and collagen fiber content). The femoral neck mechanical properties (maximum load and tenacity) were also impaired in the diabetic rats. Insulin therapy partially reversed the damage induced by diabetes on the structural properties of the bone and mitigated the reductions in the mechanical properties of the bone. The combination of therapies further increased the femoral neck trabecular bone volume (∼30%), trabecular thickness (∼24%), collagen type I (∼19%) and type III (∼13%) fiber contents, maximum load (∼25%) and tenacity (∼14%). CONCLUSIONS: Eight weeks of swimming training potentiates the recovery of femoral neck strength in young rats with severe streptozotocin-induced diabetes under insulin therapy.

Thermoregulation in Hypertensive Rats during Exercise: Effects of Physical Training / Termorregulação durante o Exercício em Ratos Hipertensos: Efeitos do Treinamento Físico

Abstract Background: Spontaneously hypertensive rats (SHR) show deficit in thermal balance during physical exercise. Objective: To assess the effects of low-intensity physical exercise training on thermal balance of hypertensive rats undergoing an acute exercise protocol. Methods: Sixteen-week-old male Wistar rats and SHR were allocated into four groups: control Wistar rats (C-WIS), trained Wistar (T-WIS), control SHR (C-SHR) and trained SHR (T-SHR). Treadmill exercise training was performed for 12 weeks. Blood pressure, resting heart rate and total exercise time was measured before and after the physical exercise program. After the exercise program, a temperature sensor was implanted in the abdominal cavity, and the animals subjected to an acute exercise protocol, during which internal body temperature, tail skin temperature and oxygen consumption until fatigue were continuously recorded. Mechanical efficiency (ME), work, heat dissipation threshold and sensitivity were calculated. Statistical significance was set at 5%. Results: Physical training and hypertension had no effect on thermal balance during physical exercise. Compared with C-WIS, the T-WIS group showed higher heat production, which was counterbalanced by higher heat dissipation. Hypertensive rats showed lower ME than normotensive rats, which was not reversed by the physical training. Conclusion: Low-intensity physical training did not affect thermal balance in SHR subjected to acute exercise.

Resumo Fundamento: Ratos espontaneamente hipertensos (SHR) apresentam déficits no balanço térmico durante o exercício físico. Objetivo: Avaliar os efeitos do treinamento físico de baixa intensidade sobre o balanço térmico de ratos hipertensos submetidos a um protocolo de exercício físico agudo. Métodos: Ratos machos Wistar e SHR, com 16 semanas de idade, foram divididos em quatro grupos experimentais: Wistar controle (WIS-C), Wistar treinado (WIS-T), SHR controle (SHR-C) e SHR treinado (SHR-T). O treinamento físico em esteira rolante foi realizado durante 12 semanas. A pressão arterial, a frequência cardíaca de repouso e o tempo de exercício foram medidos previamente e após o programa de treinamento físico. Após o programa de treinamento físico, um sensor de temperatura foi implantado na região intraperitoneal e os ratos foram submetidos a um protocolo de exercício físico agudo com registros contínuos da temperatura corporal interna, temperatura da pele da cauda e do consumo de oxigênio até a fadiga. A eficiência mecânica (EM), o trabalho, o limiar e a sensibilidade para dissipação de calor foram calculados. Para as análises estatísticas o nível de significância adotado foi de 5%. Resultados: O treinamento físico e a hipertensão arterial não alteraram o balanço térmico durante o exercício físico. O grupo WIS-T quando comparado ao WIS-C, apresentou maior produção de calor, que foi contrabalanceado por uma maior dissipação de calor. Os animais hipertensos apresentaram menor EM em comparação aos animais normotensos, e o treinamento físico não foi capaz de reverter esta alteração. Conclusão: O treinamento físico de baixa intensidade não provocou alterações no balanço térmico de ratos hipertensos submetidos a um protocolo de exercício físico agudo.

Thermoregulation in Hypertensive Rats during Exercise: Effects of Physical Training.

BACKGROUND: Spontaneously hypertensive rats (SHR) show deficit in thermal balance during physical exercise. OBJECTIVE: To assess the effects of low-intensity physical exercise training on thermal balance of hypertensive rats undergoing an acute exercise protocol. METHODS: Sixteen-week-old male Wistar rats and SHR were allocated into four groups: control Wistar rats (C-WIS), trained Wistar (T-WIS), control SHR (C-SHR) and trained SHR (T-SHR). Treadmill exercise training was performed for 12 weeks. Blood pressure, resting heart rate and total exercise time was measured before and after the physical exercise program. After the exercise program, a temperature sensor was implanted in the abdominal cavity, and the animals subjected to an acute exercise protocol, during which internal body temperature, tail skin temperature and oxygen consumption until fatigue were continuously recorded. Mechanical efficiency (ME), work, heat dissipation threshold and sensitivity were calculated. Statistical significance was set at 5%. RESULTS: Physical training and hypertension had no effect on thermal balance during physical exercise. Compared with C-WIS, the T-WIS group showed higher heat production, which was counterbalanced by higher heat dissipation. Hypertensive rats showed lower ME than normotensive rats, which was not reversed by the physical training. CONCLUSION: Low-intensity physical training did not affect thermal balance in SHR subjected to acute exercise.

Estresse térmico ambiental e termorregulação em jogadores de futebol: uma revisão sistemática / Environmental thermal stress and thermoregulation in soccer players: a systematic review / Estrés térmico ambiental y termorregulación en jugadores de fútbol: una revisión sistemática

Resumo O objetivo do estudo foi fazer uma revisão sistemática acerca dos efeitos do estresse térmico ambiental sobre a termorregulação em jogadores de futebol. Foram avaliados estudos em bases de dados pertencentes ao portal Periódicos Capes. Foi empregado o método Prisma para o desenvolvimento da revisão. Jogadores de futebol apresentam grande aumento da temperatura corporal associada à redução de desempenho físico durante o jogo em ambiente quente. Em relação às estratégias para amenizar esse prejuízo (ex. resfriamento, hidratação, aclimatação e aquecimento), o pequeno número de trabalhos encontrado (n = 18) apresenta resultados controversos, portanto são necessários mais estudos.

Abstract The objective of the study was to systematically review the effects of the environmental thermal stress on thermoregulation in soccer players. We analyzed studies from databases belonging to the Periódicos Capes portal. The PRISMA method was used to perform the review. Soccer players exhibit high increase in body temperature associated with reduction in physical performance during game in warm environment. Concerning strategies to mitigate such impairment (e.g. cooling, hydration, acclimatization, warm up and heating), the small number of studies analyzed (n = 18) showed controversial results, which warrants more studies.

Resumen El objetivo del estudio fue llevar a cabo una revisión sistemática sobre los efectos del estrés térmico ambiental en la termorregulación de jugadores de fútbol. Se evaluaron estudios en bases de datos pertenecientes al portal Periódicos Capes. Se empleó el método PRISMA para el desarrollo de la revisión. Los jugadores de fútbol presentan un gran aumento de la temperatura corporal asociada con la reducción de rendimiento físico durante el juego en un entorno caluroso. En cuanto a las estrategias para disminuir esta alteración (p. ej., enfriamiento, hidratación, aclimatación y calentamiento), el pequeño número de trabajos encontrados (n= 18) presentan resultados controvertidos, por lo que es necesaria la realización de más estudios.

Effects of aerobic exercise on the inflammatory cytokine profile and expression of lipolytic and thermogenic genes in ß1-AR-/- mice adipose tissue.

AIM: Investigate the effects of moderate continuous aerobic exercise (MCAE) on the inflammatory cytokine profile and expression of lipolytic and thermogenic genes in ß1-AR-/- mice adipose tissue. MAIN METHODS: Four- to five-month-old male wild type (WT) and ß1-AR-/- mice were divided into groups: WT control (WTc) and trained (WTt); and ß1-AR-/- control (ß1-AR-/-c) and trained (ß1-AR-/-t). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. After euthanasia, white epididymal (eWAT) and inguinal (iWAT) and brown (BAT) adipose tissues were dissected and used to determine: adiposity index; adipocyte histomorphometry; cytokine concentration; and gene expression. The content of fat, protein and water of the empty carcass was determined. KEY FINDINGS: MCAE reduced body weight, fat mass as well as iWAT and BAT adipocyte area in ß1-AR-/- animals. Aerobic exercise also diminished the concentrations of pro-inflammatory (IL-12p70, TNF-α, IL-6) and anti-inflammatory (IL-10) cytokines in adipose tissue (iWAT, eWAT or BAT) of ß1-AR-/- mice. However, MCAE had no effect on the expression lipolytic and thermogenic genes in ß1-AR-/- mice adipose tissue. SIGNIFICANCE: Alongside reductions in body weight, fat mass and adipocyte area eight weeks of MCAE improves the profile of inflammatory cytokines in ß1-AR-/- mice adipose tissue, despite no change in Lipolytic and thermogenic gene expression.

Swimming training potentiates the recovery of femoral neck strength in young diabetic rats under insulin therapy

OBJECTIVE: To test whether swimming training benefits femoral neck strength in young diabetic rats under insulin therapy. METHODS: A total of 60 male Wistar rats (age: 40 days) were divided equally into the following six groups: control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary plus insulin and diabetic exercise plus insulin. Diabetes was induced with a unique intraperitoneal injection (60 mg/kg body weight) of streptozotocin. Seven days after the injection and after 12 hours of fasting, the animals with blood glucose levels ≥300 mg/dL were considered diabetic. Seven days after the induction of diabetes, the animals in the exercise groups were subjected to progressive swimming training (final week: 90 min/day; 5 days/week; 5% load) for eight weeks. The animals in the insulin groups received a daily dose of insulin (2-4 U/day) for the same period. RESULTS: Severe streptozotocin-induced diabetes reduced the structural properties of the femoral neck (trabecular bone volume, trabecular thickness and collagen fiber content). The femoral neck mechanical properties (maximum load and tenacity) were also impaired in the diabetic rats. Insulin therapy partially reversed the damage induced by diabetes on the structural properties of the bone and mitigated the reductions in the mechanical properties of the bone. The combination of therapies further increased the femoral neck trabecular bone volume (∼30%), trabecular thickness (∼24%), collagen type I (∼19%) and type III (∼13%) fiber contents, maximum load (∼25%) and tenacity (∼14%). CONCLUSIONS: Eight weeks of swimming training potentiates the recovery of femoral neck strength in young rats with severe streptozotocin-induced diabetes under insulin therapy.

Physical Exercise and Regulation of Intracellular Calcium in Cardiomyocytes of Hypertensive Rats / Exercício Físico e Regulação de Cálcio Intracelular em Cardiomiócitos de Ratos Hipertensos

Abstract Background: Regulation of intracellular calcium (Ca2+) in cardiomyocytes is altered by hypertension; and aerobic exercise brings benefits to hypertensive individuals. Objective: To verify the effects of aerobic exercise training on contractility and intracellular calcium (Ca2+) transients of cardiomyocytes and on the expression of microRNA 214 (miR-214) in the left ventricle of spontaneously hypertensive rats (SHR). Methods: SHR and normotensive Wistar rats of 16 weeks were divided into 4 groups -sedentary hypertensive (SH); trained hypertensive (TH); sedentary normotensive (SN); and trained normotensive (TN). Animals of the TH and TN groups were subjected to treadmill running program, 5 days/week, 1 hour/day at 60-70% of maximum running velocity for 8 weeks. We adopted a p ≤ 0.05 as significance level for all comparisons. Results: Exercise training reduced systolic arterial pressure in hypertensive rats. In normotensive rats, exercise training reduced the time to 50% cell relaxation and the time to peak contraction and increased the time to 50% decay of the intracellular Ca2+ transients. In SHR, exercise increased the amplitude and reduced the time to 50% decay of Ca2+ transients. Exercise training increased the expression of miR-214 in hypertensive rats only. Conclusion: The aerobic training applied in this study increased the availability of intracellular Ca2+ and accelerated the sequestration of these ions in left ventricular myocytes of hypertensive rats, despite increased expression of miR-214 and maintenance of cell contractility.

Resumo Fundamento: A regulação intracelular de cálcio (Ca2+) em cardiomiócitos é alterada pela hipertensão, e o exercício físico aeróbico traz benefícios para hipertensos. Objetivo: Verificar os efeitos do treinamento físico aeróbico sobre a contratilidade e a concentração intracelular de Ca2+ transitória em miócitos e a expressão do microRNA 214 no ventrículo esquerdo (VE) de ratos espontaneamente hipertensos (SHR). Métodos: SHR e ratos Wistar normotensos com 16 semanas de idade foram divididos em 4 grupos de 13 animais cada: hipertenso sedentário (HS); hipertenso treinado (HT); normotenso sedentário (NS); normotenso treinado (NT). Os animais dos grupos HT e NT foram submetidos a um programa de treinamento progressivo de corrida em esteira, 5 dias/semana, 1 hora/dia, em intensidade de 60-70% da velocidade máxima de corrida, durante 8 semanas. Adotou-se p ≤ 0,05 como nível de significância em todas as comparações. Resultados: O treinamento físico reduziu a pressão arterial sistólica nos animais hipertensos. Nos animais normotensos, o treinamento físico reduziu o tempo para 50% de relaxamento celular e o tempo para o pico de contração celular, mas aumentou o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória. Nos animais SHR, o treinamento físico aumentou a amplitude e reduziu o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória, sem alterar a contratilidade celular. O treinamento físico aumentou a expressão do miR-214 apenas nos animais hipertensos. Conclusão: O treinamento aeróbico utilizado aumenta a disponibilidade e acelera o sequestro de Ca2+ intracelular em miócitos do VE de ratos hipertensos, apesar do aumento da expressão de miR-214 e da manutenção da contratilidade celular.

Physical Exercise and Regulation of Intracellular Calcium in Cardiomyocytes of Hypertensive Rats.

BACKGROUND: Regulation of intracellular calcium (Ca2+) in cardiomyocytes is altered by hypertension; and aerobic exercise brings benefits to hypertensive individuals. OBJECTIVE: To verify the effects of aerobic exercise training on contractility and intracellular calcium (Ca2+) transients of cardiomyocytes and on the expression of microRNA 214 (miR-214) in the left ventricle of spontaneously hypertensive rats (SHR). METHODS: SHR and normotensive Wistar rats of 16 weeks were divided into 4 groups -sedentary hypertensive (SH); trained hypertensive (TH); sedentary normotensive (SN); and trained normotensive (TN). Animals of the TH and TN groups were subjected to treadmill running program, 5 days/week, 1 hour/day at 60-70% of maximum running velocity for 8 weeks. We adopted a p ≤ 0.05 as significance level for all comparisons. RESULTS: Exercise training reduced systolic arterial pressure in hypertensive rats. In normotensive rats, exercise training reduced the time to 50% cell relaxation and the time to peak contraction and increased the time to 50% decay of the intracellular Ca2+ transients. In SHR, exercise increased the amplitude and reduced the time to 50% decay of Ca2+ transients. Exercise training increased the expression of miR-214 in hypertensive rats only. CONCLUSION: The aerobic training applied in this study increased the availability of intracellular Ca2+ and accelerated the sequestration of these ions in left ventricular myocytes of hypertensive rats, despite increased expression of miR-214 and maintenance of cell contractility.

Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte Contractility in Β1 Adrenergic Receptor Knockout Mice / Treinamento Aeróbico Contínuo de Intensidade Moderada Melhora a Contratilidade do Cardiomiócito em Camundongos com Nocaute para o Receptor B1-Adrenérgico

Abstract Background: The lack of cardiac β1-adrenergic receptors (β1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF. Objective: We tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from β1 adrenergic receptor knockout (β1ARKO) mice. Methods: Four- to five-month-old male wild type (WT) and β1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and β1ARKO control (β1ARKOc) and trained (β1ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. Results: The β1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The β1ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from β1ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in β1ARKO mice. Conclusion: MCAE improves myocyte contractility in the left ventricle of β1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving β1-AR desensitization or reduction.

Resumo Fundamento: A falta de receptores β1-adrenérgicos (β1-AR) cardíacos afeta negativamente a regulação de inotropismo e lusitropismo cardíacos, levando, no longo prazo, a insuficiência cardíaca (IC). Recomenda-se exercício aeróbico contínuo de intensidade moderada (EACM) como adjuvante no tratamento de pacientes com IC. Objetivo: Testar os efeitos do EACM nas propriedades contráteis de miócitos do ventrículo esquerdo (VE) de camundongos com nocaute para o receptor β1-adrenérgico (β1ARKO). Método: Camundongos machos com 4 a 5 meses de idade, wild-type (WT) e β1ARKO foram divididos em grupos: WT controle (WTc) e treinado (WTt); e β1ARKO controle (β1ARKOc) e treinado (β1ARKOt). Os grupos treinados foram submetidos a regime de EACM (60 min/dia; 60% da velocidade máxima, 5 dias/semana) em esteira rolante, por 8 semanas. Adotou-se P ≤ 0,05 como nível de significância em todas as comparações. Resultados: Os animais β1ARKO (β1ARKOc + β1ARKOt) correram uma distância maior do que os animais WT (WTc + WTt) (p < 0,05). Os camundongos β1ARKO apresentaram maiores pesos corporal (PC), do coração (PCo) e do ventrículo esquerdo (PVE), assim como PCo/PC e PVE/PC do que os camundongos WT. Entretanto, o EACM não afetou tais parâmetros. Os miócitos do VE de camundongos β1ARKO apresentaram maiores (p < 0,05) amplitude e velocidades de contração e relaxamento do que os dos camundongos WT. Além disso, o EACM aumentou (p < 0,05) a amplitude e as velocidades de contração e relaxamento nos camundongos β1ARKO. Conclusão: O EACM melhora a contratilidade do miócito do VE de camundongos β1ARKO. Tal achado confirma o valor terapêutico desse tipo de treinamento físico para o tratamento de doenças cardíacas envolvendo dessensibilização ou redução de β1-AR.

Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte Contractility in Β1 Adrenergic Receptor Knockout Mice.

BACKGROUND: The lack of cardiac ß1-adrenergic receptors (ß1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF. OBJECTIVE: We tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from ß1 adrenergic receptor knockout (ß1ARKO) mice. METHODS: Four- to five-month-old male wild type (WT) and ß1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and ß1ARKO control (ß1ARKOc) and trained (ß1ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. RESULTS: The ß1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The ß1ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from ß1ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in ß1ARKO mice. CONCLUSION: MCAE improves myocyte contractility in the left ventricle of ß1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving ß1-AR desensitization or reduction.

Power spectrum analysis of cardiovascular variability during passive heating in conscious rats.

The cardiovascular system plays a direct role in the maintenance of body temperature. Whether passive heating alters cardiovascular autonomic modulation in conscious rats is still unknown. This study investigated the effects of passive heating on systolic blood pressure variability (SBPV) and heart rate variability (HRV) in conscious rats and the involvement of the renin-angiotensin system in the passive heating effects on SBPV and HRV. Fourteen male Wistar rats were randomly assigned to the control group or the losartan treatment group. A catheter was implanted in the left carotid artery to record pulsatile arterial pressure (PAP), and a telemetry sensor was implanted in the abdominal cavity to measure body temperature (Tbody). After recovering from surgery, the animals were subjected to a passive heating protocol (35°C; 30min) in resting conditions, during which Tbody, tail skin temperature and PAP were measured. The mean arterial pressure, systolic and diastolic blood pressure, heart rate, double product (i.e., the product of systolic blood pressure by heart rate), SBPV and HRV were calculated from the PAP. SBPV and HRV were analyzed in terms of both time and frequency domains. Increases in the thermoregulatory and cardiovascular parameters were observed during passive heating in both groups, and those increases were reflected in the higher time and frequency domains of the SBPV. However, passive heating was not effective in altering HRV. Passive heating altered SBPV but not HRV in conscious rats when they were treated with losartan.

Brain Temperature in Spontaneously Hypertensive Rats during Physical Exercise in Temperate and Warm Environments.

This study aimed to evaluate brain temperature (Tbrain) changes in spontaneously hypertensive rats (SHRs) subjected to two different physical exercise protocols in temperate or warm environments. We also investigated whether hypertension affects the kinetics of exercise-induced increases in Tbrain relative to the kinetics of abdominal temperature (Tabd) increases. Male 16-week-old normotensive Wistar rats (NWRs) and SHRs were implanted with an abdominal temperature sensor and a guide cannula in the frontal cortex to enable the insertion of a thermistor to measure Tbrain. Next, the animals were subjected to incremental-speed (initial speed of 10 m/min; speed was increased by 1 m/min every 3 min) or constant-speed (60% of the maximum speed) treadmill running until they were fatigued in a temperate (25°C) or warm (32°C) environment. Tbrain, Tabd and tail skin temperature were measured every min throughout the exercise trials. During incremental and constant exercise at 25°C and 32°C, the SHR group exhibited greater increases in Tbrain and Tabd relative to the NWR group. Irrespective of the environment, the heat loss threshold was attained at higher temperatures (either Tbrain or Tabd) in the SHRs. Moreover, the brain-abdominal temperature differential was lower at 32°C in the SHRs than in the NWRs during treadmill running. Overall, we conclude that SHRs exhibit enhanced brain hyperthermia during exercise and that hypertension influences the kinetics of the Tbrain relative to the Tabd increases, particularly during exercise in a warm environment.

ÓXIDO NÍTRICO E DINÂMICA DE CA2+ EM CARDIOMIÓCITOS: INFLUÊNCIA DA CAPACIDADE DE EXERCÍCIO / NITRIC OXIDE AND CA2+ DYNAMICS IN CARDIOMYOCYTES: INFLUENCE OF EXERCISE CAPACITY / ÓXIDO NÍTRICO Y DINAMICA DE CA2+ EN CARDIOMIOCITOS: INFLUENCIA DE LA CAPACIDAD DE EJERCÍCIO

RESUMO Introdução: A capacidade intrínseca para o exercício aeróbico está relacionada com o inotropismo cardíaco. Por outro lado, a participação do óxido nítrico (NO) como mensageiro intracelular sobre a dinâmica do Ca2+ ainda permanece desconhecida em ratos com diferentes capacidades intrínsecas para o exercício. Objetivo: Avaliar se o NO modula diferentemente o transiente intracelular de Ca2+ e liberações espontâneas de Ca2+(sparks) em cardiomiócitos de ratos com diferentes capacidades intrínsecas para o exercício. Métodos: Ratos machos Wistar foram selecionados como desempenho padrão (DP) e alto desempenho (AD), de acordo com a capacidade de exercício até a fadiga, mensurada através de teste de esforço progressivo em esteira. Os cardiomiócitos dos ratos foram utilizados para determinar o transiente intracelular de Ca2+ e Ca2+sparks em microscópio confocal. Para estimar a contribuição do NO foi utilizado o inibidor das sínteses do NO (L-NAME, 100 µM). Os dados foram analisados através de ANOVA two-way seguido do pós-teste de Tukey e apresentados como médias ± EPM. Resultados: Os cardiomiócitos de ratos AD exibiram aumentos na amplitude do transiente de Ca2+ em comparação aos DP. Entretanto, o L-NAME aumentou a amplitude do transiente de Ca2+ somente em ratos DP. Não foram encontradas diferenças na constante de tempo de decaimento do transiente de Ca2+ (t) em cardiomiócitos de ratos com DP e AP, contudo, a administração do L-NAME diminuiu o t em cardiomiócitos em ambos os grupos. cardiomiócitos de ratos AD apresentaram menor amplitude e frequência de Ca2+sparks em comparação ao grupo DP. A administração de L-NAME aumentou a amplitude de Ca2+sparks em cardiomiócitos do grupo AD. Conclusão: O NO modula o transiente de Ca2+ e as sparks de Ca2+ em cardiomiócitos de ratos com diferentes capacidades intrínsecas para o exercício.

ABSTRACT Introduction: The intrinsic capacity to aerobic exercise is associated with cardiac inotropism. On the other hand, the contribution of nitric oxide (NO) as an intracellular messenger on Ca2+ dynamics remains unknown in rats with different intrinsic capacities to exercise. Objective: To evaluate whether NO modulates differently Ca2+ intracellular transient and spontaneous Ca2+ releases (sparks) in cardiomyocytes of rats with different intrinsic capacities to exercise. Methods: Male Wistar rats were selected as standard-performance (SP) and high-performance (HP), according to the exercise capacity until fatigue, assessed through a treadmill progressive stress test. Cardiomyocytes of rats were used to determine Ca2+ intracellular transient and Ca2+ sparks evaluated using confocal microscope. To estimate NO contribution, a NO synthase inhibitor (L-NAME, 100 µM) was used. Data were analyzed through two-way ANOVA followed by Tukey's post hoc test and expressed as means ± SEM. Results: Cardiomyocytes of HP rats exhibited higher Ca2+ transient amplitude compared to SP. However, L-NAME increased Ca2+ transient amplitude only in SP rats. No differences were found in Ca2+ transient decay time constant ( t) in cardiomyocytes of SP and HP rats. However, administration of L-NAME caused reduction of tin cardiomyocytes of both groups. Lower amplitude and frequency of Ca2+ sparks were found in cardiomyocytes of HS rats compared to SP group. Administration of L-NAME increased the amplitude of Ca2+ sparks in cardiomyocytes of the HP group. Conclusion: NO modulates Ca2+ transient and Ca2+ sparks in cardiomyocytes of rats with different intrinsic exercise capacities.

RESUMEN Introducción: La capacidad intrínseca para el ejercicio aeróbico está relacionada con el inotropismo cardiaco. Por otro lado, todavía se desconoce la contribución del óxido nítrico (ON) como mensajero intracelular sobre la dinámica del Ca2+ en ratones con diferentes capacidades intrínsecas para el ejercicio. Objetivo: Evaluar si el ON modula diferencialmente la variación transitoria intracelular de Ca2+ y las liberaciones espontaneas de Ca2+ (sparks) en cardiomiocitos de ratones con diferentes capacidades intrínsecas para el ejercicio. Métodos: Ratones machos Wistar fueron seleccionados como desempeño estándar (DE) y alto desempeño (AD), de acuerdo con la capacidad de ejercicio hasta la fatiga, medida a través del test de fuerza progresiva en la caminadora o cinta eléctrica. Los cardiomiocitos de los ratones fueron utilizados para determinar el tránsito intracelular y sparks de Ca2+ evaluados en microscopio confocal. Para estimar la contribución del ON fue utilizado un inhibidor de síntesis del ON (L-NAME, 100 µM). Los datos fueron analizados a través de un ANOVA two-way seguido de un post-test Tukey y presentados como promedios ± EPM. Resultados: Los cardiomiocitos de ratones AD mostraron aumento en la amplitud de la variación transitoria de Ca2+ en comparación con los DE. Así mismo, el L-NAME incremento la amplitud transitoria de Ca2+ solamente en ratones DE. No se encontraron diferencias en la constante del tiempo de decaimiento de la variación transitoria ( t ) de Ca2+ en cardiomiocitos de ratones DE e AD. Todavía, la administración de L-NAME mostro una reducción en el t en cardiomiocitos de ambos los grupos. Cardiomiocitos de ratones AD presentaron menor amplitud y frecuencia de sparks de Ca2+ en comparación al grupo DE. La administración de L-NAME incrementó la amplitud de sparks de Ca2+ en cardiomiocitos del grupo AD. Conclusión: El ON modula la variación de Ca2+ y sparks de Ca2+ en cardiomiocitos de ratones con diferentes capacidades intrínsecas para el ejercicio.

Mesenchymal stem cell therapy associated with endurance exercise training: Effects on the structural and functional remodeling of infarcted rat hearts.

We tested the effects of early mesenchymal stem cell (MSC) therapy associated with endurance exercise on the structural and functional cardiac remodeling of rats with myocardial infarctation (MI). Male Wistar rats (40 days old) were divided into 6 groups: control and exercise sham; control and exercise MI; and control and exercise MI MSC. MI was surgically induced and bone marrow-derived MSCs were immediately injected via caudal vein (concentration: 1 × 10(6 )cells). Twenty-four hours later ET groups exercised on a treadmill (5 days/week; 60 min/day; 60% of maximal running velocity) for 12 weeks. Structural and functional changes were determined by echocardiography. Contractility and intracellular global calcium ([Ca(2 +)]i) transient were measured in myocytes from the left ventricular (LV) non-infarcted area. Calcium regulatory proteins were measured by Western blot. MI increased (p < 0.05) heart, ventricular and LV weights and its ratios to body weight; LV internal dimension in diastole (LVID-D) and in systole (LVID-S) and LV free wall in diastole (LVFW-D), but reduced the thickness of interventricular septum in systole (IVS-S), ejection fraction (EF) and fractional shortening (FS). MI augmented (p < 0.05) the times to peak and to half relaxation of cell shortening as well as the amplitude of the [Ca(2 +)]i transient and the times to peak and to half decay. Early MSCs therapy restored LVFW-D, IVS-S and the amplitude and time to half decay of the [Ca(2 +)]i transient. Early endurance exercise intervention increased (p < 0.05) LVFW-S, IVS-S, EF and FS, and reduced the times to peak and to half relaxation of cell shortening, and the amplitude of the [Ca(2 +)]i transient. Exercise training also increased the expression of left ventricular SERCA2a and PLBser16. Nevertheless, the combination of these therapies did not cause additive effects. In conclusion, combining early MSCs therapy and endurance exercise does not potentiate the benefits of such treatments to structural and functional cardiac remodeling in infarcted rats.