Clinical significance of cardiac damage and changes in function after exercise

Acute bouts of ultraendurance exercise may result in the appearance of biomarkers of cardiac cell damage and a transient reduction in left ventricular function. The clinical significance of these changes is not fully understood. There seems to be two competing issues to be resolved. First, could prolonged endurance exercise produce a degree of cardiac stress and/or damage that results, during the short or long term, in deleterious consequences for cardiac health. Second, there is a clear need to educate those responsible for the medical care of endurance athletes about the possibility of a transient reduction in cardiac function and the appearance of cTnT/cTnI after an exercise. Minor elevations in cardiac troponins are commonplace after an endurance exercise in elite and recreational athletes and may occur alongside exercise-associated collapse. Misdiagnosis of myocardial injury and subsequent mismanagement can be unnecessarily expensive and psychologically damaging to the athlete. Diagnosis of myocardial injury after prolonged exercise should be made on the basis of all available information and not blood tests alone. The clinical significance of chronic exposure to endurance exercise is unknown. The development of myocardial fibrosis has been suggested as a long-term outcome to chronic exposure to repetitive bouts of endurance exercise and has been linked to an exercise-induced inflammatory process observed in an animal model. This hypothesis is supported by a limited number of studies reporting postmortem studies in athletes and an increased prevalence of complex arrhythmia in veteran athletes. Care is warranted in promoting this hypothesis without further detailed work, given the unequivocal link between exercise and mortality and morbidity. It would seem erroneous, however, to assume that a linear relationship exists between exercise volume and cardiac health.     

Exercise and immune function. Recent developments

Comparison of immune function in athletes and nonathletes reveals that the adaptive immune system is largely unaffected by athletic endeavour. The innate immune system appears to respond differentially to the chronic stress of intensive exercise, with natural killer cell activity tending to be enhanced while neutrophil function is suppressed. However, even when significant changes in the level and functional activity of immune parameters have been observed in athletes, investigators have had little success in linking these to a higher incidence of infection and illness. Many components of the immune system exhibit change after prolonged heavy exertion. During this 'open window' of altered immunity (which may last between 3 and 72 hours, depending on the parameter measured), viruses and bacteria may gain a foothold, increasing the risk of subclinical and clinical infection. However, no serious attempt has been made by investigators to demonstrate that athletes showing the most extreme post-exercise immunosuppression are those that contract an infection during the ensuing 1 to 2 weeks. This link must be established before the 'open window' theory can be wholly accepted. The influence of nutritional supplements, primarily zinc, vitamin C, glutamin and carbohydrate, on the acute immune response to prolonged exercise has been measured in endurance athletes. Vitamin C and glutamine have received much attention, but the data thus far are inconclusive. The most impressive results have been reported in the carbohydrate supplementation studies. Carbohydrate beverage ingestion has been associated with higher plasma glucose levels, an attenuated cortisol and growth hormone response, fewer perturbations in blood immune cell counts, lower granulocyte and monocyte phagocytosis and oxidative burst activity, and a diminished pro- and anti-inflammatory cytokine response. It remains to be shown whether carbohydrate supplementation diminishes the frequency of infections in the recovery period after strenuous exercise. Studies on the influence of moderate exercise training on host protection and immune function have shown that near-daily brisk walking compared with inactivity reduced the number of sickness days by half over a 12- to 15-week period without change in resting immune function. Positive effects on immunosurveillance and host protection that come with moderate exercise training are probably related to a summation effect from acute positive changes that occur during each exercise bout. No convincing data exist that moderate exercise training is linked with improved T helper cell counts in patients with HIV, or enhanced immunity in elderly participants.     

Ultra‐endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function

Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra‐endurance exercise‐induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra‐endurance exercise, there were significant increases in leukocytes, platelets, interleukin‐6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase‐9. Ultra‐endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein‐Barr virus was seen to be reactivated in one of seven athletes. The link between exercise‐induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra‐endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration.     

Nutrition, exercise, and immune system function.

Many components of the immune system exhibit adverse change after prolonged, intense exertion. During this "open window" of impaired immunity (which may last 3-72 h, depending on the immune measure), viruses and bacteria may gain a foothold, increasing the risk for subclinical and clinical infection. The influence of nutritional supplements, primarily zinc, vitamin C, glutamine, and carbohydrate, on the acute immune response to prolonged exercise has been measured in endurance athletes. Vitamin C and glutamine have received much attention, but the data thus far are inconclusive. The most impressive results have been reported with carbohydrate supplementation. Carbohydrate beverage ingestion has been associated with increased plasma glucose levels, an attenuated cortisol and growth hormone response, fewer perturbations in blood immune cell counts, decreased granulocyte and monocyte phagocytosis and oxidative burst activity, and a diminished pro-inflammatory and anti-inflammatory cytokine response. Overall these data indicate that the physiologic stress to the immune system is reduced when endurance athletes use carbohydrate beverages before, during, and after prolonged and intense exertion. The clinical significance of these carbohydrate-induced effects on the endocrine and immune systems awaits further research.     

Plasma amino acid concentrations in the overtraining syndrome: possible effects on the immune system.

Overtraining and long-term exercise are associated with an impairment of immune function. We provide evidence in support of the hypothesis that the supply of glutamine, a key fuel for cells of the immune system, is impaired in these conditions and that this may contribute to immunosuppression. Plasma glutamine concentration was decreased in overtrained athletes and after long-term exercise (marathon race) and was increased after short-term, high intensity exercise (sprinting). Branched chain amino acid supplementation during long-term exercise was shown to prevent this decrease in the plasma glutamine level. Overtraining was without effect on the rate of T-lymphocyte proliferation in vitro or on the plasma levels of interleukin-1 and -6, suggesting that immune function is not impaired in this condition. Given the proposed importance of glutamine for cells of the immune system, it is concluded that the decrease in plasma glutamine concentration in overtraining and following long-term exercise, and not an intrinsic defect in T lymphocyte function, may contribute to the immune deficiency reported in these conditions.     

Plasma glutamine responses to high-intensity exercise before and after endurance training

Glutamine responses to strenuous interval exercise were examined before and after 6 weeks of endurance training. Glutamine measures were obtained before and after the interval exercise sessions and training in untrained males assigned to training (T; n = 10) or control (C; n = 10) groups. Before training, C and T group glutamine progressively decreased (p < 0.05) by 18% and 16%, respectively, by 150-min postinterval exercise. Over the training period C group glutamine did not change, while T group values increased (p < 0.05) by 14%. After training, glutamine again decreased (p < 0.05) by similar percentages (C = 16% and T = 15%) by 150-min postinterval exercise, but the T group recorded higher (p < 0.05) resting and postexercise glutamine concentrations than the C group. Training induced increases in glutamine may prevent the decline in glutamine levels following strenuous exercise falling below a threshold where immune function might be acutely compromised.     

Cardiac troponin T release after prolonged strenuous exercise

Over the past 2 decades, there has been a large interest in cardiac troponin T (cTnT) elevations, which are often seen following endurance sport events. There have been many reports on this topic, although sometimes with different approaches. We reviewed the available literature on cTnT elevations after prolonged strenuous exercise and discovered profound differences in the percentage of subjects reported to have elevated cTnT concentrations. This could partly be attributed to differences in immunoassay characteristics, such as cross-reactivity with skeletal troponin T, and the use of different cut-off values used in the different studies. The elevations were transient, with levels decreasing to pre-event concentrations within 24-48 hours. This might be explained by the relatively short half-life of cTnT, or water imbalance during and after the event. The release mechanism of cTnT, as well as the long-term positive or negative effects, remains unclear. Future research should therefore be aimed at clarifying the release mechanism of cTnT. Furthermore, the benefits and the possible long-term negative aspects of prolonged exercise should be evaluated.     

Exercise-induced increases in cardiac troponins and prothrombotic markers

Cardiac troponin I and T are potent tools for risk stratification and clinical decision-making for patients in the appropriate clinical setting of an acute coronary syndrome. Although these findings are relevant to patients with a typical clinical presentation, caution should be exercised in generalizing the results to troponin-positive athletes with a low clinical suspicion of coronary artery disease. This review addresses the clinical relevance of increased troponin levels induced by strenuous exercise. The imprecision and lack of standardization of currently available troponin assays merit caution with the application of these findings. In addition, it may well be that if reparative processes are present and/or the release is not due to irreversible injury that increases in troponins after vigorous exercise are normal and should not be expected to be of pathophysiological significance. Due to this potential for misclassification, the crux of appropriate interpretation of troponin testing is careful consideration of the corresponding clinical scenario. Troponin-positive patients often have complex coronary lesion morphology with intracoronary thrombus and understandably derive particular benefit from platelet glycoprotein GpIIb/IIa inhibitors as well as low molecular weight heparins. Studies on exercise-induced activation of blood coagulation have produced conflicting results. At present, there is no clear evidence that a hemostatic imbalance may trigger acute cardiac events after strenuous exercise. In contrast to troponin-positive patients, it may thus be premature and even dangerous to recommend pharmacologic intervention (low molecular weight heparins) to (troponin-positive) endurance athletes even when exercising during high-altitude exposure.     

Exercise-associated increases in cardiac biomarkers

At present, the risk of myocardial damage by endurance exercise is under debate because of reports on exercise-associated increases in cardiac biomarkers troponin and B-type natriuretic peptide (BNP); these markers are typically elevated in patients with acute myocardial infarction and chronic heart failure, respectively. Exercise-associated elevations of cardiac biomarkers can be present in elite and in recreational athletes, especially after prolonged and strenuous endurance exercise bouts (e.g., marathon and ultratriathlon). However, in contrast to cardiac patients, it is still unclear if the exercise-associated appearance or increase in cardiac biomarkers in obviously healthy athletes represents clinically significant cardiac insult or is indeed part of the physiological response to endurance exercise. In addition, elevations in cardiac biomarkers in athletes after exercise may generate difficulties for clinicians in terms of differential diagnosis and may result in inappropriate consequences. Therefore, the aim of this article is to provide an overview of exercise-associated alterations of the cardiac biomarkers troponin T and I, ischemia-modified albumin, BNP, and its cleaved inactive fragment N-terminal pro BNP for the athlete, coach, scientist, and clinician.     

The effect of BCAA supplementation upon the immune response of triathletes

INTRODUCTION: Intense long-duration exercise could lead to immune suppression through a decrease in the circulating level of plasma glutamine. The decrease in plasma glutamine concentration as a consequence of intense long-duration exercise was reversed, in some cases, by supplementing the diet of the athletes with branched-chain amino acids (BCAA). To better address this question, we have evaluated some blood parameters (lymphocyte proliferation, the level of plasma cytokines, plasma glutamine concentration, and in vitro production of cytokines by peripheral blood lymphocytes) before and after the S?o Paulo International Triathlon, as well as the incidence of symptoms of infections between the groups. METHODS: Twelve elite male triathletes of mean age 25.5 +/- 3.2 yr (ranging from 21.4 to 30.1 yr), weighing 74.16 +/- 3.9 kg, swam 1.5 km, cycled 40 km, and ran 10 km (Olympic triathlon) in the S?o Paulo International Triathlon held in April 1997 and April 1998. In both events, six athletes received BCAA and the others, placebo. RESULTs: Athletes from the BCAA group (BG) presented the same levels of plasma glutamine, before and after the trial, whereas those from the placebo group showed a reduction of 22.8% in plasma glutamine concentration after the competition. Changes in the proliferative response of peripheral blood lymphocytes were accompanied by a reduction in IL-1 production after exercise (22.2%), which was reversed by BCAA supplementation (20.3%), without changes in IL-2 production. DISCUSSION: The data obtained show that BCAA supplementation can reverse the reduction in serum glutamine concentration observed after prolonged intense exercise such as an Olympic triathlon. The decrease in plasma glutamine concentration is paralleled by an increased incidence of symptoms of infections that results in augmented proliferative response of lymphocytes cultivated in the absence of mitogens. The prevention of the lowering of plasma glutamine concentration allows an increased response of lymphocytes to ConA and LPS, as well as an increased production of IL-1 and 2, TNF-alpha, and IFN-gamma, possibly linked to the lower incidence of symptoms of infection (33.84%) reported by the supplemented athletes.     

Effects of exercise on lymphocytes and cytokines

OBJECTIVES: To review results on exercise induced changes in the immune system following strenuous and moderate exercise. METHODS: A literature search over the past 15 years was conducted using Medline and selected papers. RESULTS: After intense long term exercise, the immune system is characterised by concomitant impairment of the cellular immune system and increased inflammation. Thus low concentrations of lymphocytes, suppressed natural immunity, suppressed lymphocyte proliferation, and suppressed levels of secretory IgA in saliva are found simultaneously with high levels of circulating proinflammatory and antiinflammatory cytokines. The underlying mechanisms are multifactorial and include neuroendocrinological and metabolic factors. The clinical consequences of the exercise induced immune changes have not formally been identified, but the exercise effect on lymphocyte dynamics and immune function may be linked to the exercise effects on resistance to infections and malignancy and the cytokine response may be linked to muscle damage or muscle cell growth. CONCLUSIONS: Moderate exercise across the life span seems to increase resistance to upper respiratory tract infections, whereas repeated strenuous exercise suppresses immune function. It is premature to offer advice on nutrition to athletes in order to alter the exercise induced immunosuppression found after exercise.     

Exercise immunology: the current state of man and mouse

The mechanisms governing the body's response to physical exercise have been investigated from various perspectives including metabolism, nutrition, age and sex. Increased attention to the immune system during recent decades is reflected by a rapidly growing number of publications in the field. This article highlights the most recent findings and only briefly summarises more basic concepts already reviewed by others. Topics include Th1/Th2 cytokine balance, inoculation time, age and immune compensation. Some less investigated areas are discussed including studies in children, the environment and dendritic cells. Because physical exercise enhances some aspects and suppresses other aspects of immunity, the biological significance of alterations in the immune system are unknown. So far, no link between immunological alterations and infection rate has been established and infection after strenuous physical exercise is equally likely to be the result of exercising with an already established rather than a new infection. If there is an increased risk for infections with increased exercise duration and intensity, why do overtrained athletes not display the greatest risk for upper respiratory tract infections? Increased knowledge on immune system modulations with physical exercise is relevant both from a public health and elite athlete's point of view.     

Free fatty acid and glucose metabolism during increased energy expenditure and after training.

The amount of fat available as substrate to provide the energy needed for submaximal exercise is almost unlimited; therefore, it stands to reason that the organism will adapt so that it uses fat as the major energy substrate during very prolonged exercise. Nevertheless, the quantitatively smaller body stores of carbohydrate, which contain only one to two percent as many calories as the fat stores, play a very important role during exercise, since depletion of either muscle or liver glycogen will force an individual to terminate strenuous muscular work. In normal dogs during long-lasting exercise, at energy expenditures ranging from the resting state of 0.73 kcal/m2 min to a work load of 4.66 kcal/m2 min, the FFA mobilization, and participation of FFA oxidation in total energy expenditure increases. During prolonged exercise in trained dogs, 50-90% of the energy may derive from plasma FFA, while plasma glucose contributes not more than 10% to the energy expenditure. However, there is an inverse relationship between the amount of glycogen stored inside the muscle, its rate of depletion, and muscular endurance during prolonged strenuous work. Oxidation of FFA spares muscle glycogen and in this way increases work endurance.     

Endothelial function in post-menopausal former elite athletes.

OBJECTIVE: To characterize endothelial function in postmenopausal former elite athletes in comparison to sedentary controls and to study the influence of hormone replacement therapy (HRT) on endothelial function in these groups of women. DESIGN: Cross-sectional study. SETTING: Research unit at a university hospital. PARTICIPANTS: Twenty postmenopausal former elite but still active endurance female athletes and 19 age-matched sedentary controls. The group of athletes and control subjects were each subdivided into two groups on the basis of utilization or non-utilization of HRT involving estrogen and gestagen. METHODS: Flow-mediated vasodilatation (FMD) was employed as an indicator of endothelial function. Fasting blood samples were analyzed for lipids and body composition determined by dual-energy x-ray absorptiometry. MAIN OUTCOME MEASURES: FMD, blood lipids and body composition. RESULTS: Former elite athletes not utilizing HRT demonstrated the highest FMD of all four subgroups, their values being significantly higher than those of control subjects not utilizing HRT (P < 0.05), whereas this difference was not seen between the subgroups of athletes and control subjects using HRT. Serum levels of cholesterol and low-density lipoprotein (LDL) and the percentage of fat mass were significantly lower in the former elite athletes than in the control group (P < 0.05 in all cases). However, these variables were not related to FMD. CONCLUSION: This investigation documents enhanced endothelial function in postmenopausal former elite endurance athletes not utilizing HRT, whereas the use of HRT equalizes FMD in former athletes and sedentary control subjects. Our findings suggest that long-term strenuous exercise has beneficial effects on endothelial function in postmenopausal women but that no further improvement can be obtained with HRT.     

Biochemical changes as a result of prolonged strenuous exercise

OBJECTIVE: To briefly review biochemical changes that may result from prolonged strenuous exercise and to relate these changes to health risk. METHODS: Medline and Sports Discus databases were searched for relevant articles. Additional articles were found using cross referencing and the authors' knowledge of the subject area. RESULTS: Prolonged strenuous exercise may result in a series of biochemical changes that are of concern from a health point of view. Generally, these changes are benign, but some, especially hyponatraemia, are potentially life threatening occurrences. CONCLUSION: Doctors and athletes should be aware of the potentially adverse biochemical changes, especially hyponatraemia, that may result from prolonged strenuous exercise.     

Effect of endurance training on lung function: a one year study

Objective: To identify in a follow up study airway changes occurring during the course of a sport season in healthy endurance athletes training in a Mediterranean region. Methods: Respiratory pattern and function were analysed in 13 healthy endurance trained athletes, either during a maximal exercise test, or at rest and during recovery through respiratory manoeuvres (spirometry and closing volume tests). The exercise test was conducted on three different occasions: during basic endurance training and then during the precompetition and competitive periods. Results: During the competitive period, a slight but non-clinically significant decrease was found in forced vital capacity (–3.5%, p = 0.0001) and an increase in slope of phase III (+25%, p = 0.0029), both at rest and after exercise. No concomitant reduction in expiratory flow rates was noticed. During maximal exercise there was a tachypnoeic shift over the course of the year (mean (SEM) breathing frequency and tidal volume were respectively 50 (2) cycles/min and 3.13 (0.09) litres during basic endurance training v 55 (3) cycles/min and 2.98 (0.10) litres during the competitive period; p<0.05). Conclusions: This study does not provide significant evidence of lung function impairment in healthy Mediterranean athletes after one year of endurance training.     

Voluntary training in mice and submandibular lymphocyte response to acute exercise

INTRODUCTION: Submandibular lymph nodes (SLN) are important for immune responses to antigens in the eye and oral mucosa. Athletes and exercise participants may be at increased risk of ocular, oral, and upper respiratory tract infections. PURPOSE: This study was conducted to examine the effects of voluntary training on the distribution, number, and apoptotic status of SLN lymphocytes in response to an acute bout of strenuous exercise. METHODS: Female C57BL/6 mice were assigned to voluntary wheel-running (WR) exercise (N=20) or were sedentary (N=10) for 16 wk. SLN lymphocytes were examined immediately (EX+Imm) or 24 h (EX+24 h) following strenuous treadmill exercise, or exposure to treadmill conditions without running (NonEX). Intracellular glutathione (GSH), mitochondrial membrane potential (MMP), cell viability (propidium iodide uptake, PI), surface phosphatidylserine (Annexin V), T-lymphocyte (CD3, CD4, CD8), and B-lymphocyte (CD19) phenotype distribution and number were assessed. RESULTS: The WR mice had a higher number and percent CD8 SLN lymphocytes, higher MMP, and lower Annexin V/PI SLN lymphocytes than controls. Regardless of training status, an acute bout of strenuous exercise decreased the total and phenotype specific (CD3, CD4, CD8) number of cells, MMP, and GSH levels immediately after exercise. CONCLUSION: WR in mice improved some aspects of cell viability in SLN lymphocytes compared with controls, but did not prevent the transient cell loss after acute treadmill exercise. Given the depletion in intracellular GSH levels, oxidative stress may account for the decline in SLN lymphocyte numbers following acute exercise. Loss of SLN lymphocytes may have consequences for ocular, oral, and upper respiratory tract health in some exercise participants and athletes during periods of overtraining.     

Echocardiography and the Athlete's Heart

In brief: Echocardiographic studies permit direct, accurate measurements of the ventricular wall thickness and cavity diameter. The authors review several of these studies, which show that elite athletes' left ventricles are larger than those of sedentary persons. Left ventricular wall thickness is greater in athletes excelling in sports involving static exercise, whereas those in endurance sports have larger ventricular cavities. These differences in cardiac dimensions may be the result of genetic makeup, prolonged and strenuous training, or a combination of both. Studies of short-term training showed only minor or no changes in left ventricular morphology, although significant improvements in performance and aerobic capacity were reported.     

Upper respiratory tract infections: who plays,who sits?

In athletes with upper respiratory infections (URIs), the question of who plays and who sits can be difficult to answer. Acute exercise suppresses several aspects of the immune system. None of these immunologic changes, however, consistently correlate with the incidence of URIs in athletes. The risk of infection with exercise seems to follow a J-curve relationship, with regular, moderate exercisers having a lower risk than sedentary people, and regular, strenuous exercisers having the highest risk of all. The decision to allow an athlete to play or not can be guided by the "neck check" rules, and can also take into account nonmedical factors. The athlete with infectious mononucleosis warrants more careful attention, as there are strict guidelines for return-to-play in these individuals, to avoid the possibility of splenic rupture.