Heat and exercise acclimation increases intracellular levels of Hsp72 and inhibits exercise-induced increase in intracellular and plasma Hsp72 in humans

In order to verify the effects of heat and exercise acclimation (HA) on resting and exercise-induced expression of plasma and leukocyte heat shock protein 72 (Hsp72) in humans, nine healthy young male volunteers (25.0 +/- 0.7 years; 80.5 +/- 2.0 kg; 180 +/- 2 cm, mean +/- SE) exercised for 60 min in a hot, dry environment (40 +/- 0A degrees C and 45 A +/- 0% relative humidity) for 11 days. The protocol consisted of running on a treadmill using a controlled hyperthermia technique in which the work rate was adjusted to elevate the rectal temperature by 1A degrees C in 30 min and maintain it elevated for another 30 min. Before and after the HA, the volunteers performed a heat stress test (HST) at 50% of their individual maximal power output for 90 min in the same environment. Blood was drawn before (REST), immediately after (POST) and 1 h after (1 h POST) HST, and plasma and leukocytes were separated and stored. Subjects showed expected adaptations to HA: reduced exercise rectal and mean skin temperatures and heart rate, and augmented sweat rate and exercise tolerance. In HST1, plasma Hsp72 increased from REST to POST and then returned to resting values 1 h POST (REST: 1.11 A +/- 0.07, POST: 1.48 A +/- 0.10, 1 h POST: 1.22 A +/- 0.11 ng mL(-1); p < 0.05). In HST2, there was no change in plasma Hsp72 (REST: 0.94 A +/- 0.08, POST: 1.20 A +/- 0.15, 1 h POST: 1.17 A +/- 0.16 ng mL(-1); p > 0.05). HA increased resting levels of intracellular Hsp72 (HST1: 1 A +/- 0.02 and HST2: 4.2 A +/- 1.2 density units, p < 0.05). Exercise-induced increased intracellular Hsp72 expression was observed on HST1 (HST1: REST, 1 A +/- 0.02 vs. POST, 2.9 A +/- 0.9 density units, mean +/- SE, p < 0.05) but was inhibited on HST2 (HST2: REST, 4.2 +/- 1.2 vs. POST, 4.4 +/- 1.1 density units, p > 0.05). Regression analysis showed that the lower the pre-exercise expression of intracellular Hsp72, the higher the exercise-induced increase (R = -0.85, p < 0.05). In conclusion, HA increased resting leukocyte Hsp72 levels and inhibited exercise-induced expression. This intracellular adaptation probably induces thermotolerance. In addition, the non-increase in plasma Hsp72 after HA may be related to lower stress at the cellular level in the acclimated individuals.

Involvement of the TRPV1 channel in the modulation of spontaneous locomotor activity, physical performance and physical exercise-induced physiological responses

Physical exercise triggers coordinated physiological responses to meet the augmented metabolic demand of contracting muscles. To provide adequate responses, the brain must receive sensory information about the physiological status of peripheral tissues and organs, such as changes in osmolality, temperature and pH. Most of the receptors involved in these afferent pathways express ion channels, including transient receptor potential (TRP) channels, which are usually activated by more than one type of stimulus and are therefore considered polymodal receptors. Among these TRP channels, the TRPV1 channel (transient receptor potential vanilloid type 1 or capsaicin receptor) has well-documented functions in the modulation of pain sensation and thermoregulatory responses. However, the TRPV1 channel is also expressed in non-neural tissues, suggesting that this channel may perform a broad range of functions. In this review, we first present a brief overview of the available tools for studying the physiological roles of the TRPV1 channel. Then, we present the relationship between the TRPV1 channel and spontaneous locomotor activity, physical performance, and modulation of several physiological responses, including water and electrolyte balance, muscle hypertrophy, and metabolic, cardiovascular, gastrointestinal, and inflammatory responses. Altogether, the data presented herein indicate that the TPRV1 channel modulates many physiological functions other than nociception and thermoregulation. In addition, these data open new possibilities for investigating the role of this channel in the acute effects induced by a single bout of physical exercise and in the chronic effects induced by physical training.

The roles of exercise-induced immune system disturbances in the pathology of heat stroke - The dual pathway model of heat stroke

Heat stroke is a life-threatening condition that can be fatal if not appropriately managed. Although heat stroke has been recognised as a medical condition for centuries, a universally accepted definition of heat stroke is lacking and the pathology of heat stroke is not fully understood. Information derived from autopsy reports and the clinical presentation of patients with heat stroke indicates that hyperthermia, septicaemia, central nervous system impairment and cardiovascular failure play important roles in the pathology of heat stroke. The current models of heat stroke advocate that heat stroke is triggered by hyperthermia but is driven by endotoxaemia. Endotoxaemia triggers the systemic inflammatory response, which can lead to systemic coagulation and haemorrhage, necrosis, cell death and multi-organ failure. However, the current heat stroke models cannot fully explain the discrepancies in high core temperature (Tc) as a trigger of heat stroke within and between individuals. Research on the concept of critical Tc: as a limitation to endurance exercise implies that a high Tc may function as a signal to trigger the protective mechanisms against heat stroke. Athletes undergoing a period of intense training are subjected to a variety of immune and gastrointestinal (GI) disturbances. The immune disturbances include the suppression of immune cells and their functions, suppression of cell-mediated immunity, translocation of lipopolysaccharide (LPS), suppression of anti-LPS antibodies, increased macrophage activity due to muscle tissue damage, and increased concentration of circulating inflammatory and pyrogenic cytokines. Common symptoms of exercise-induced GI disturbances include diarrhoea, vomiting, gastrointestinal bleeding, and cramps, which may increase gut-related LPS translocation. This article discusses the current evidence that supports the argument that these exercise-induced immune and GI disturbances may contribute to the development of endotoxaemia and heat stroke. When endotoxaemia can be tolerated or prevented, continuing exercise and heat exposure will elevate Tc to a higher level (> 42 degrees C), where heat stroke may occur through the direct thermal effects of heat on organ tissues and cells. We also discuss the evidence suggesting that heat stroke may occur through endotoxaemia (heat sepsis), the primary pathway of heat stroke, or hyperthermia, the secondary pathway of heat stroke. The existence of these two pathways of heat stroke and the contribution of exercise-induced immune and GI disturbances in the primary pathway of heat stroke are illustrated in the dual pathway model of heat stroke. This model of heat stroke suggests that prolonged intense exercise suppresses anti-LPS mechanisms, and promotes inflammatory and pyrogenic activities in the pathway of heat stroke.

Effect of 655-nm Low-Level Laser Therapy on Exercise-Induced Skeletal Muscle Fatigue in Humans

Objective: To investigate if development of skeletal muscle fatigue during repeated voluntary biceps contractions could be attenuated by low-level laser therapy (LLLT). Background Data: Previous animal studies have indicated that LLLT can reduce oxidative stress and delay the onset of skeletal muscle fatigue. Materials and Methods: Twelve male professional volleyball players were entered into a randomized double-blind placebo-controlled trial, for two sessions (on day 1 and day 8) at a 1-wk interval, with both groups performing as many voluntary biceps contractions as possible, with a load of 75% of the maximal voluntary contraction force (MVC). At the second session on day 8, the groups were either given LLLT (655 nm) of 5 J at an energy density of 500 J/cm(2) administered at each of four points along the middle of the biceps muscle belly, or placebo LLLT in the same manner immediately before the exercise session. The number of muscle contractions with 75% of MVC was counted by a blinded observer and blood lactate concentration was measured. Results: Compared to the first session (on day 1), the mean number of repetitions increased significantly by 8.5 repetitions (+/- 1.9) in the active LLLT group at the second session (on day 8), while in the placebo LLLT group the increase was only 2.7 repetitions (+/- 2.9) (p = 0.0001). At the second session, blood lactate levels increased from a pre-exercise mean of 2.4 mmol/L (+/- 0.5 mmol/L), to 3.6 mmol/L (+/- 0.5 mmol/L) in the placebo group, and to 3.8 mmol/L (+/- 0.4 mmol/L) in the active LLLT group after exercise, but this difference between groups was not statistically significant. Conclusion: We conclude that LLLT appears to delay the onset of muscle fatigue and exhaustion by a local mechanism in spite of increased blood lactate levels.

Effects of Ipratropium on Exercise-Induced Bronchospasm

Exercise-induced bronchospasm (EIB) is the transient narrowing of the airways that follows vigorous exercise. Ipratropium bromide may be used to prevent EIB, but its effect varies among individuals. We hypothesized that time of administration of ipratropium interferes with its action. This was a prospective, double-blind, cross-over study carried out to evaluate the bronchoprotective and bronchodilatory effect of ipratropium at different times of day. The study consisted of 4 exercise challenge tests (2 at 7 am and 2 at 6 pm). In the morning, one of the tests was performed after placebo administration and the other one after ipratropium (80 mu g) and the two tests (placebo and ipratropium) were repeated in the evening. Twenty-one patients with severe or moderate asthma and previous confirmation of EIB were enrolled in this prospective trial. The bronchodilatory effect of ipratropium was 0.25 +/- 0.21 L or 13.11 +/- 10.99 % (p = 0.001 compared to baseline values) in the morning, and 0.14 +/- 0.25 L or 7.25 +/- 11.37 % (p > 0.05) in the evening. In the morning, EIB was 0.58 +/- 0.29 L on the placebo day and 0.38 +/- 0.22 L on the treatment day (p = 0.01). In the evening, EIB was 0.62 +/- 0.28 L on the placebo day and 0.51 +/- 0.35 L on the treatment day (p > 0.05). We suggest that the use of ipratropium for the treatment of asthma and EIB should take into consideration the time of administration.

Exercise-induced alterations in neutrophil degranulation and respiratory burst activity: possible mechanisms of action

Neutrophils constitute 50-60% of all circulating leukocytes; they present the first line of microbicidal defense and are involved in inflammatory responses. To examine immunocompetence in athletes, numerous studies have investigated the effects of exercise on the number of circulating neutrophils and their response to stimulation by chemotactic stimuli and activating factors. Exercise causes a biphasic increase in the number of neutrophils in the blood, arising from increases in catecholamine and cortisol concentrations. Moderate intensity exercise may enhance neutrophil respiratory burst activity, possibly through increases in the concentrations of growth hormone and the inflammatory cytokine IL-6. In contrast, intense or long duration exercise may suppress neutrophil degranulation and the production of reactive oxidants via elevated circulating concentrations of epinephrine (adrenaline) and cortisol. There is evidence of neutrophil degranulation and activation of the respiratory burst following exercise-induced muscle damage. In principle, improved responsiveness of neutrophils to stimulation following exercise of moderate intensity could mean that individuals participating in moderate exercise may have improved resistance to infection. Conversely, competitive athletes undertaking regular intense exercise may be at greater risk of contracting illness. However there are limited data to support this concept. To elucidate the cellular mechanisms involved in the neutrophil responses to exercise, researchers have examined changes in the expression of cell membrane receptors, the production and release of reactive oxidants and more recently, calcium signaling. The investigation of possible modifications of other signal transduction events following exercise has not been possible because of current methodological limitations. At present, variation in exercise-induced alterations in neutrophil function appears to be due to differences in exercise protocols, training status, sampling points and laboratory assay techniques.

Endogenous endothelin-1 limits exercise-induced vasodilation in hypertensive humans

Essential hypertension is a common disorder, associated with increased endothelin-l-mediated vasoconstrictor tone at rest. We hypothesized that increased vasoconstrictor activity of endothelin-1 might explain why the normal decrease in peripheral vascular resistance in response to exercise is attenuated in hypertensive patients. Therefore, we investigated the effect of endothelin A (ETA) receptor blockade on the vasodilator response to handgrip exercise. Forearm blood flow responses to handgrip exercise (15%, 30%, and 45% of maximum voluntary contraction) were assessed in hypertensive patients and matched normotensive subjects, before and after intra-arterial infusions of the ETA receptor antagonist BQ-123; a control dilator, hydralazine; and placebo (saline). Preinfusion (baseline) vasodilation in response to exercise was significantly attenuated at each workload in hypertensive patients compared with normotensive subjects. Intra-arterial infusions of hydralazine and saline did not increase the vasodilator response to exercise in either hypertensives or normotensives at any workload. The vasodilator response to exercise was markedly enhanced after BQ-123 at the 2 higher workloads in hypertensives (157 +/- 48%, P < 0.01; 203 &PLUSMN; 58%, P < 0.01) but not in normotensives. This suggests that the impaired vasodilator response to exercise in hypertensive patients is, at least in part, a functional limitation caused by endogenous ETA receptor-mediated vasoconstriction. Treatment with endothelin receptor antagonists may, therefore, increase exercise capacity in essential hypertension.

The evidence of conventional physiotherapeutic interventions after exercise-induced muscle damage: systematic review and meta-analysis

Abstract Introduction: Exhaustive and/or unaccustomed exercise, mainly those involving eccentric muscle actions, induces temporary muscle damage, evidenced by Delayed Onset Muscle Soreness. Different strategies to recover the signs and symptoms of this myogenic condition have been studied by researchers, as a result a significant number of articles on this issue have been published. Purpose: A systematic review was conducted to assess the evidence of the physiotherapeutic interventions of exercise-induced muscle damage. Methods: The electronic data bases were searched, including MEDLINE (1996-2011), CINHAL (1982- 2011), EMBASE (1988-2011), PEDro (1950-2011), and SPORTDiscus (1985-2011). Systematic review was limited to randomized control trials (RCTs) studies, written in English or Portuguese, which included physiotherapeutic interventions, namely massage, cryotherapy, stretching and low-intensity exercise, on adult human subjects (18-60 years old) of either gender. Studies were excluded when the intervention could not be assessed independently. The methodological quality of RCTs was independently assessed with the PEDro Scale by three reviewers. Results: Thirty-three studies were included in the systematic review; eight analyzed the effects of the massage, ten analyzed the effects of the cryotherapy, eight the effect of stretching and seventeen focused low-intensity exercise intervention. The results suggest that massage is the most effective intervention and that there is inconclusive evidence to support the use of cryotherapy; whereas the other conventional, namely stretching and low-intensity exercise, there is no evidence to prove their efficacy. Conclusion: The results allow the conclusion that massage is the physiotherapeutic intervention that demonstrated to be the most effective in the relief of symptoms and signs of exercise-induced muscle damage, as a result, massage should still be used in the muscular recovery after sports activities.

Exercise-Induced Intraventricular Obstruction in a Child with Near Syncope and Chest Pain During Exercise

We report the case of a 10-year-old girl with two episodes of light-headedness and chest pain during exercise. She had an unremarkable clinical record, physical examination, ECG, and echocardiogram. Noninvasive ischemia tests were positive, but coronary angiography was normal. Exercise stress echocardiogram revealed an exercise-induced intra-left-ventricular obstruction with a peak gradient of 78 mmHg and replicated her symptoms. After starting beta-blocker therapy her clinical status improved and no residual obstruction was detected. The authors review this unsuspected clinical condition, seldom reported in the adult population and, to our knowledge, never before in a child.

Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease patients with no apparent cardiac involvement

INTRODUCTION : Exercise-induced ventricular arrhythmia (EIVA) and autonomic imbalance are considered as early markers of heart disease in Chagas disease (ChD) patients. The objective of the present study was to verify the differences in the occurrence of EIVA and autonomic maneuver indexes between healthy individuals and ChD patients with no apparent cardiac involvement. METHODS : A total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5) years, and 38 healthy individuals, aged 44.0 (9.2) years, were evaluated using echocardiography, symptom-limited treadmill exercise testing and autonomic function tests. RESULTS : The occurrence of EIVA was higher in the chagasic group (48%) than in the control group (23.7%) during both the effort and the recovery phases. Frequent ventricular contractions occurred only in the patient group. Additionally, the respiratory sinus arrhythmia index was significantly lower in the chagasic individuals compared with the control group. CONCLUSIONS : ChD patients with no apparent cardiac involvement had a higher frequency of EIVA as well as more vagal dysfunction by respiratory sinus arrhythmia. These results suggest that even when asymptomatic, ChD patients possess important arrhythmogenic substrates and subclinical disease.

Mechanisms Involved in Exercise-Induced Cardioprotection: A Systematic Review

Background:Acute myocardial infarction is the leading cause of morbidity and mortality worldwide. Furthermore, research has shown that exercise, in addition to reducing cardiovascular risk factors, can also protect the heart against injury due to ischemia and reperfusion through a direct effect on the myocardium. However, the specific mechanism involved in exerciseinduced cardiac preconditioning is still under debate.Objective:To perform a systematic review of the studies that have addressed the mechanisms by which aerobic exercise promotes direct cardioprotection against ischemia and reperfusion injury.Methods:A search was conducted using MEDLINE, Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde, and Scientific Electronic Library Online databases. Data were extracted in a standardized manner by two independent researchers, who were responsible for assessing the methodological quality of the studies.Results:The search retrieved 78 studies; after evaluating the abstracts, 30 studies were excluded. The manuscripts of the remaining 48 studies were completely read and, of these, 20 were excluded. Finally, 28 studies were included in this systematic review.Conclusion:On the basis of the selected studies, the following are potentially involved in the cardioprotective response to exercise: increased heat shock protein production, nitric oxide pathway involvement, increased cardiac antioxidant capacity, improvement in ATP-dependent potassium channel function, and opioid system activation. Despite all the previous investigations, further research is still necessary to obtain more consistent conclusions.

Effects of flecainide on exercise-induced ventricular arrhythmias and recurrences in genotype-negative patients with catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND: Conventional therapy with beta-blockers is incompletely effective in preventing arrhythmic events in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). We have previously discovered that flecainide in addition to conventional drug therapy prevents ventricular arrhythmias in patients with genotype-positive CPVT. OBJECTIVE: To study the efficacy of flecainide in patients with genotype-negative CPVT. METHODS: We studied the efficacy of flecainide for reducing ventricular arrhythmias during exercise testing and preventing arrhythmia events during long-term follow-up. RESULTS: Twelve patients with genotype-negative CPVT were treated with flecainide. Conventional therapy failed to control ventricular arrhythmias in all patients. Flecainide was initiated because of significant ventricular arrhythmias (n = 8), syncope (n = 3), or cardiac arrest (n = 1). At the baseline exercise test before flecainide, 6 patients had ventricular tachycardia and 5 patients had bigeminal or frequent ventricular premature beats. Flecainide reduced ventricular arrhythmias at the exercise test in 8 patients compared to conventional therapy, similar to that in patients with genotype-positive CPVT in our previous report. Notably, flecainide completely prevented ventricular arrhythmias in 7 patients. Flecainide was continued in all patients except for one who had ventricular tachycardia at the exercise test on flecainide. During a follow-up of 48±94 months, arrhythmia events (sudden cardiac death and aborted cardiac arrest) associated with noncompliance occurred in 2 patients. Flecainide was not discontinued owing to side effects in any of the patients. CONCLUSIONS: Flecainide was effective in patients with genotype-negative CPVT, suggesting that spontaneous Ca(2+) release from ryanodine channels plays a role in arrhythmia susceptibility, similar to that in patients with genotype-positive CPVT.

Local moderate magnetically induced hyperthermia using an implant formed in situ in a mouse tumor model.

Purpose: We investigate a new heat delivery technique for the local treatment of solid tumors. The technique involves injecting a formulation that solidifies to form an implant in situ. This implant entraps superparamagnetic iron oxide nanoparticles (SPIONs) embedded in silica microbeads for magnetically induced moderate hyperthermia. Particle entrapment prevents phagocytosis and distant migration of SPIONs. The implant can be repeatedly heated by magnetic induction. Methods: We evaluated heating and treatment efficacies by means of thermometry and survival studies in nude mice carrying subcutaneous human colocarcinomas. At day 1, we injected the formulation into the tumor. At day 2, a single 20-min hyperthermia treatment was delivered by 141-kHz magnetic induction using field strengths of 9 to 12 mT under thermometry. Results: SPIONs embedded in silica microbeads were effectively confined within the implant at the injection site. Heat-induced necro-apoptosis was assessed by histology on day 3. On average, 12 mT resulted in tumor temperature of 47.8 degrees C, and over 70% tumor necrosis that correlated to the heat dose (AUC = 282 degrees C.min). In contrast, a 9-mT field strength induced tumoral temperature of 40 degrees C (AUC = 131 degrees C.min) without morphologically identifiable necrosis. Survival after treatment with 10.5 or 12 mT fields was significantly improved compared to non-implanted and implanted controls. Median survival times were 27 and 37 days versus 12 and 21 days respectively. Conclusion: Five of eleven mice (45%) of the 12 mT group survived one year without any tumor recurrence, holding promise for tumor therapy using magnetically induced moderate hyperthermia through injectable implants.

RV contractility and exercise-induced pulmonary hypertension in chronic mountain sickness: a stress echocardiographic and tissue Doppler imaging study.

OBJECTIVES: The aim of this study was to evaluate right ventricular (RV) and left ventricular function and pulmonary circulation in chronic mountain sickness (CMS) patients with rest and stress echocardiography compared with healthy high-altitude (HA) dwellers. BACKGROUND: CMS or Monge's disease is defined by excessive erythrocytosis (hemoglobin >21 g/dl in males, 19 g/dl in females) and severe hypoxemia. In some cases, a moderate or severe increase in pulmonary pressure is present, suggesting a similar pathogenesis of pulmonary hypertension. METHODS: In La Paz (Bolivia, 3,600 m sea level), 46 CMS patients and 40 HA dwellers of similar age were evaluated at rest and during semisupine bicycle exercise. Pulmonary artery pressure (PAP), pulmonary vascular resistance, and cardiac function were estimated by Doppler echocardiography. RESULTS: Compared with HA dwellers, CMS patients showed RV dilation at rest (RV mid diameter: 36 ± 5 mm vs. 32 ± 4 mm, CMS vs. HA, p = 0.001) and reduced RV fractional area change both at rest (35 ± 9% vs. 43 ± 9%, p = 0.002) and during exercise (36 ± 9% vs. 43 ± 8%, CMS vs. HA, p = 0.005). The RV systolic longitudinal function (RV-S') decreased in CMS patients, whereas it increased in the control patients (p < 0.0001) at peak stress. The RV end-systolic pressure-area relationship, a load independent surrogate of RV contractility, was similar in CMS patients and HA dwellers with a significant increase in systolic PAP and pulmonary vascular resistance in CMS patients (systolic PAP: 50 ± 12 mm Hg vs. 38 ± 8 mm Hg, CMS vs. HA, p < 0.0001; pulmonary vascular resistance: 2.9 ± 1 mm Hg/min/l vs. 2.2 ± 1 mm Hg/min/l, p = 0.03). Both groups showed comparable systolic and diastolic left ventricular function both at rest and during stress. CONCLUSIONS: Comparable RV contractile reserve in CMS and HA suggests that the lower resting values of RV function in CMS may represent a physiological adaptation to chronic hypoxic conditions rather than impaired RV function. (Chronic Mountain Sickness, Systemic Vascular Function [CMS]; NCT01182792).