Exercise Training In Humans Research Articles

Physiological regulation linked with physical activity and health

Physiological regulation linked with physical activity and health

Time-course of Conduit Arterial Structure and Function Adaptation To Exercise Training in Humans

Time-course of Conduit Arterial Structure and Function Adaptation To Exercise Training in Humans

Time course of change in vasodilator function and capacity in response to exercise training in humans

Studies of the impact of exercise training on arterial adaptation in healthy subjects have produced disparate results. It is possible that some studies failed to detect changes because functional and structural adaptations follow a different time course and may therefore not be detected at discrete time points. To gain insight into the time course of training-induced changes in artery function and structure, we examined conduit artery flow mediated dilatation (FMD), an index of nitric oxide (NO)-mediated artery function, and conduit dilator capacity (DC), a surrogate marker for arterial remodelling, in the brachial and popliteal arteries of 13 healthy male subjects (21.6 +/- 0.6 years) and seven non-active controls (22.8 +/- 0.2 years) studied at 2-week intervals across an 8-week cycle and treadmill exercise training programme. Brachial and popliteal artery FMD and DC did not change in control subjects at any time point. FMD increased from baseline (5.9 +/- 0.5%) at weeks 2 and 4 (9.1 +/- 0.6, 8.5 +/- 0.6%, respectively, P < 0.01), but returned towards baseline levels again by week 8 (6.9 +/- 0.7%). In contrast, brachial artery DC progressively increased from baseline (8.1 +/- 0.4%) at weeks 2, 4, 6 and 8 (9.2 +/- 0.6, 9.9 +/- 0.6, 10.0 +/- 0.5, 10.5 +/- 0.8%, P < 0.05). Similarly, popliteal artery FMD increased from baseline (6.2 +/- 0.7%) at weeks 2, 4 and 6 (9.1 +/- 0.6, 9.5 +/- 0.6, 7.8 +/- 0.5%, respectively, P < 0.05), but decreased again by week 8 (6.5 +/- 0.6%), whereas popliteal DC progressively increased from baseline (8.9 +/- 0.4%) at week 4 and 8 (10.5 +/- 0.7, 12.2 +/- 0.6%, respectively, P < 0.05). These data suggest that functional changes in conduit arteries occur rapidly and precede arterial remodelling in vivo. These data suggest that complimentary adaptations occur in arterial function and structure and future studies should adopt multiple time point assessments to comprehensively assess arterial adaptations to interventions such as exercise training in humans.

Differential attenuation of AMPK activation during acute exercise following exercise training or AICAR treatment

Short-term exercise training in humans attenuates AMP-activated protein kinase (AMPK) activation during subsequent exercise conducted at the same absolute workload. Short-term 5-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR) administration in rats mimics exercise training on skeletal muscle in terms of increasing insulin sensitivity, mitochondrial enzymes, and GLUT4 content, but it is not known whether these adaptations are accompanied by reduced AMPK activation during subsequent exercise. We compared the effect of 10 days of treadmill training (60 min/day) with 10 days of AICAR administration (0.5 mg/g body weight ip) on subsequent AMPK activation during 45 min of treadmill exercise in male Sprague-Dawley rats. Compared with nonexercised control rats, acute exercise significantly (P < 0.05) increased AMPKalpha Thr172 phosphorylation (p-AMPKalpha; 1.6-fold) and ACCbeta Ser218 phosphorylation (p-ACCbeta; 4.9-fold) in the soleus and p-ACCbeta 2.2-fold in the extensor digitorum longus. Ten days of exercise training abolished the increase in soleus p-AMPKalpha and attenuated the increase in p-ACCbeta (nonsignificant 2-fold increase). Ten days of AICAR administration also attenuated the exercise-induced increases in AMPK signaling in the soleus although not as effectively as 10 days of exercise training (nonsignificant 1.3-fold increase in p-AMPKalpha; significant 3-fold increase in p-ACCbeta). The increase in skeletal muscle 2-deoxyglucose uptake during exercise was greater after either 10 days of exercise training or AICAR administration. In conclusion, 10 days of AICAR administration substantially mimics the effect of 10 days training on attenuating skeletal muscle AMPK activation in response to subsequent exercise.

Training in hypoxia and its effects on skeletal muscle tissue

It is well established that local muscle tissue hypoxia is an important consequence and possibly a relevant adaptive signal of endurance exercise training in humans. It has been reasoned that it might be advantageous to increase this exercise stimulus by working in hypoxia. However, as long-term exposure to severe hypoxia has been shown to be detrimental to muscle tissue, experimental protocols were developed that expose subjects to hypoxia only for the duration of the exercise session and allow recovery in normoxia (live low-train high or hypoxic training). This overview reports data from 27 controlled studies using some implementation of hypoxic training paradigms. Hypoxia exposure varied between 2300 and 5700 m and training duration ranged from 10 days to 8 weeks. A similar number of studies was carried out on untrained and on trained subjects. Muscle structural, biochemical and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available data on global estimates of performance capacity such as maximal oxygen uptake (VO2max) and maximal power output (Pmax), hypoxia as a supplement to training is not consistently found to be of advantage for performance at sea level. There is some evidence mainly from studies on untrained subjects for an advantage of hypoxic training for performance at altitude. Live low-train high may be considered when altitude acclimatization is not an option.

Commentary on Viewpoint: Perspective on the future use of genomics in exercise prescription

VIEWPOINTCommentary on Viewpoint: Perspective on the future use of genomics in exercise prescriptionJames A. TimmonsJames A. TimmonsPublished Online:01 Apr 2008https://doi.org/10.1152/japplphysiol.00015.2008MoreSectionsPDF (28 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat to the editor: Roth (2) concluded that genomic information could meaningfully impact on the clinical decision-making process predominantly in two of three scenarios. However, this conclusion is largely based on genetic association methods that have many limitations. In contrast, functional genomics approaches capture both genetic and environmental influences. Gene-network activation measures are an integrated signal that associates with physiological adaptation (1) in a manageable numbers of subjects for human physiological studies (3, 4). Implementation of personalized approaches is arguably most important for healthy subjects to maximize the effectiveness of preventative strategies. Functional genomics, rather than genetics, will herald in the age of personalized medicine for complex traits and, for example, allow us to prescribe tailored exercise therapy to maximize the benefits to those who can benefit from exercise, especially in scenario 1. However, I believe Dr. Roth highlights a critical issue; while aerobic training does not improve aerobic capacity in 20% of people, it will also not increase HDL in >30%. No systematic analysis allows us to be certain that a “nonresponder” for one trait does not cluster with a poor response for another. Also, not all parameters are equal; aerobic capacity links to mortality while other responses are not proven to be so important (yet). Ultimately, we have an obligation to ensure that any intervention (even exercise) is effective for the individual, and not just across a population. For the unlucky (not so small) minority, we may yet discover strategies for overcoming the molecular “limitations” that stifle physiological adaptation.REFERENCES1 Keller P, Vollaard NJB, Babraj J, Ball D, Sewell DA, Timmons JA. Using systems biology to define the essential biological networks responsible for adaptation to endurance exercise training. Biochem Soc Trans 35: 1306–1309, 2007.Crossref | PubMed | ISI | Google Scholar2 Roth SM. Viewpoint: Perspective on the future use of genomics in exercise prescription. J Appl Physiol; doi:10.1152/japplphysiol.01000.2007.Link | ISI | Google Scholar3 Timmons JA, Jansson E, Fischer H, Gustafsson T, Greenhaff PL, Ridden J, Rachman J, Sundberg CJ. Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans. BMC Biol 3: 19, 2005.Crossref | PubMed | ISI | Google Scholar4 Timmons JA, Larsson O, Jansson E, Fischer H, Gustafsson T, Greenhaff PL, Ridden J, Rachman J, Peyrard-Janvid M, Wahlestedt C, Sundberg CJ. Human muscle gene expression responses to endurance training provide a novel perspective on Duchenne muscular dystrophy. FASEB J 19: 750–760, 2005.Crossref | PubMed | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: J. A. Timmons, School of Life Sciences, John Muir Bldg., Heriot-Watt Univ., Edinburgh EH3 5EA, UK (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByGenetics and sport performance: current challenges and directions to the futureRevista Brasileira de Educação Física e Esporte, Vol. 28, No. 1Defining a molecular portrait of physical fitness30 November 2012 | Analytical and Bioanalytical Chemistry, Vol. 405, No. 1Lack of Exercise Is a Major Cause of Chronic Diseases1 April 2012Variability in training-induced skeletal muscle adaptationJames A. Timmons1 March 2011 | Journal of Applied Physiology, Vol. 110, No. 3A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotypePernille Keller, Niels B. J. Vollaard, Thomas Gustafsson, Iain J. Gallagher, Carl Johan Sundberg, Tuomo Rankinen, Steven L. Britton, Claude Bouchard, Lauren G. Koch, and James A. Timmons1 January 2011 | Journal of Applied Physiology, Vol. 110, No. 1Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humansJames A. Timmons, Steen Knudsen, Tuomo Rankinen, Lauren G. Koch, Mark Sarzynski, Thomas Jensen, Pernille Keller, Camilla Scheele, Niels B. J. Vollaard, Søren Nielsen, Thorbjörn Åkerström, Ormond A. MacDougald, Eva Jansson, Paul L. Greenhaff, Mark A. Tarnopolsky, Luc J. C. van Loon, Bente K. Pedersen, Carl Johan Sundberg, Claes Wahlestedt, Steven L. Britton, and Claude Bouchard1 June 2010 | Journal of Applied Physiology, Vol. 108, No. 6 More from this issue > Volume 104Issue 4April 2008Pages 1250-1250 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00015.2008PubMed18385305History Published online 1 April 2008 Published in print 1 April 2008 Metrics

Skeletal muscle nNOSμ protein content is increased by exercise training in humans

The major isoform of nitric oxide synthase (NOS) in skeletal muscle is the splice variant of neuronal NOS, termed nNOS mu. Exercise training increases nNOS mu protein levels in rat skeletal muscle, but data in humans are conflicting. We performed two studies to determine 1) whether resting nNOS mu protein expression is greater in skeletal muscle of 10 endurance-trained athletes compared with 11 sedentary individuals (study 1) and 2) whether intense short-term (10 days) exercise training increases resting nNOS mu protein (within whole muscle and also within types I, IIa, and IIx fibers) in eight sedentary individuals (study 2). In study 1, nNOS mu protein was approximately 60% higher (P < 0.05) in endurance-trained athletes compared with the sedentary participants. In study 2, nNOS mu protein expression was similar in types I, IIa, and IIx fibers before training. Ten days of intense exercise training significantly (P < 0.05) increased nNOS mu protein levels in types I, IIa, and IIx fibers, a finding that was validated by using whole muscle samples. Endothelial NOS and inducible NOS protein were barely detectable in the skeletal muscle samples. In conclusion, nNOS mu protein expression is greater in endurance-trained individuals when compared with sedentary individuals. Ten days of intense exercise is also sufficient to increase nNOS mu expression in untrained individuals, due to uniform increases of nNOS mu within types I, IIa, and IIx fibers.

Short‐term exercise training in humans reduces AMPK signalling during prolonged exercise independent of muscle glycogen

We examined the effect of short-term exercise training on skeletal muscle AMP-activated protein kinase (AMPK) signalling and muscle metabolism during prolonged exercise in humans. Eight sedentary males completed 120 min of cycling at 66 +/- 1% , then exercise trained for 10 days, before repeating the exercise bout at the same absolute workload. Participants rested for 72 h before each trial while ingesting a high carbohydrate diet (HCHO). Exercise training significantly (P < 0.05) attenuated exercise-induced increases in skeletal muscle free AMP: ATP ratio and glucose disposal and increased fat oxidation. Exercise training abolished the 9-fold increase in AMPK alpha2 activity observed during pretraining exercise. Since training increased muscle glycogen content by 93 +/- 12% (P < 0.01), we conducted a second experiment in seven sedentary male participants where muscle glycogen content was essentially matched pre- and post-training by exercise and a low CHO diet (LCHO; post-training muscle glycogen 52 +/- 7% less than in HCHO, P < 0.001). Despite the difference in muscle glycogen levels in the two studies we obtained very similar results. In both studies the increase in ACCbeta Ser(221) phosphorylation was reduced during exercise after training. In conclusion, there is little activation of AMPK signalling during prolonged exercise following short-term exercise training suggesting that other factors are important in the regulation of glucose disposal and fat oxidation under these circumstances. It appears that muscle glycogen is not an important regulator of AMPK activation during exercise in humans when exercise is begun with normal or high muscle glycogen levels.

Modulation of extracellular matrix genes reflects the magnitude of physiological adaptation to aerobic exercise training in humans

BackgroundRegular exercise reduces cardiovascular and metabolic disease partly through improved aerobic fitness. The determinants of exercise-induced gains in aerobic fitness in humans are not known. We have demonstrated that over 500 genes are activated in response to endurance-exercise training, including modulation of muscle extracellular matrix (ECM) genes. Real-time quantitative PCR, which is essential for the characterization of lower abundance genes, was used to examine 15 ECM genes potentially relevant for endurance-exercise adaptation. Twenty-four sedentary male subjects undertook six weeks of high-intensity aerobic cycle training with muscle biopsies being obtained both before and 24 h after training. Subjects were ranked based on improvement in aerobic fitness, and two cohorts were formed (n = 8 per group): the high-responder group (HRG; peak rate of oxygen consumption increased by +0.71 ± 0.1 L min-1; p < 0.0001) while the low-responder group (LRG; peak rate of oxygen consumption did not change, +0.17 ± 0.1 L min-1, ns). ECM genes profiled included the angiopoietin 1 and related genes (angiopoietin 2, tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1) and 2 (TIE2), vascular endothelial growth factor (VEGF) and related receptors (VEGF receptor 1, VEGF receptor 2 and neuropilin-1), thrombospondin-4, α2-macroglobulin and transforming growth factor β2.Resultsneuropilin-1 (800%; p < 0.001) and VEGF receptor 2 (300%; p < 0.01) transcript abundance increased only in the HRG, whereas levels of VEGF receptor 1 mRNA actually declined in the LRG (p < 0.05). TIE1 and TIE2 mRNA levels were unaltered in the LRG, whereas transcription levels of both genes were increased by 2.5-fold in the HRG (p < 0.01). Levels of thrombospondin-4 (900%; p < 0.001) and α2-macroglobulin (300%, p < 0.05) mRNA increased substantially in the HRG. In contrast, the amount of transforming growth factor β2 transcript increased only in the HRG (330%; p < 0.01), whereas it remained unchanged in the LRG (-80%).ConclusionWe demonstrate for the first time that aerobic training activates angiopoietin 1 and TIE2 genes in human muscle, but only when aerobic capacity adapts to exercise-training. The fourfold-greater increase in aerobic fitness and markedly differing gene expression profile in the HRG indicates that these ECM genes may be critical for physiological adaptation to exercise in humans. In addition, we show that, without careful demonstration of physiological adaptation, conclusions derived from gene expression profiling of human skeletal muscle following exercise may be of limited value. We propose that future studies should (a) investigate the mechanisms that underlie the apparent link between physiological adaptation and gene expression and (b) use the genes profiled in this paper as candidates for population genetic studies.

Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses

Interleukin-15 (IL-15) is an anabolic cytokine that is produced in skeletal muscle and directly affects muscle anabolism in animal and in vitro models. The contribution of IL-15 variability in muscle responses to 10 wk of resistance exercise training in young men and women was examined by measuring acute and chronic changes in IL-15 protein in plasma and characterizing genetic variation in the IL-15 receptor-alpha gene (IL15RA). Participants trained 3 days a week at 75% of one repetition maximum, performing three sets (6-10 repetitions) of 13 resistance exercises. Plasma IL-15 protein was significantly increased (P < 0.05) immediately after acute resistance exercise but did not change with training and was not associated with variability in muscle responses with training. A single nucleotide polymorphism in exon 7 of IL15RA was strongly associated with muscle hypertrophy and accounted for 7.1% of the variation in regression modeling. A polymorphism in exon 4 was also independently associated with muscle hypertrophy and accounted for an additional 3.5% of the variation in hypertrophy. These results suggest that IL-15 is an important mediator of muscle mass response to resistance exercise training in humans and that genetic variation in IL15RA accounts for a significant proportion of the variability in this response.

Response to aerobic exercise training in humans with neuromuscular disease.

There have been few studies examining the response of persons with neuromuscular disease and postpolio syndrome to cardiopulmonary testing and aerobic exercise training. In persons with neuromuscular disease that directly involves the cardiac and respiratory systems, deficits in performance may be primarily due to these limitations, along with loss of functional muscle tissue from the disease process. In the more slowly progressive disorders, deconditioning may play an important role in limiting aerobic exercise performance and may be amenable to training. Recommendations are provided for future exercise studies with these populations.

Response to resistive strengthening exercise training in humans with neuromuscular disease.

The role of strengthening exercise to potentially improve weakness and the functional abilities of persons with neuromuscular diseases is controversial. There are questions about the ability of diseased skeletal muscle to respond to resistance exercise, particularly in light of concerns about weakness induced by exercise. Numerous studies show promising results of strength training, although methodologic issues limit conclusions. This article reviews current knowledge in this area and provides recommendations for future investigations.

Adaptations to Exercise Training in Humans and Animals with Neuromuscular Diseases

Adaptations to Exercise Training in Humans and Animals with Neuromuscular Diseases

Mitochondrial transcription factor A and respiratory complex IV increase in response to exercise training in humans.

Protein levels of mitochondrial transcription factor A (Tfam) and nuclear- and mitochondrial-encoded subunits of respiratory chain complex IV (COX I and COX IV) as well as citrate synthase activity were analysed in muscle biopsy samples of vastus lateralis in six healthy male subjects before and after 4 weeks of one-legged cycle training. One leg was trained with restricted blood flow. The other leg was trained with the same power profile but with non-restricted blood flow. Tfam, COX I and COX IV levels all increased with training, with no differences observed between the legs. The training-induced increase in citrate synthase activity was greater in the leg trained with restricted blood flow. These findings indicate that changed expression of Tfam protein could be one mechanism of exercise-induced mitochondrial biogenesis. The increases of COX I and COX IV indicate a concurrent increase of nuclear- and mitochondrial-encoded subunits of respiratory enzyme complex IV at the protein level in skeletal muscle in response to increased muscle activity. In this study, it was not possible to demonstrate that the greater energy disturbance induced by reduced blood flow further stimulates the expression of mitochondrial proteins, even though it did cause a greater enhancement of citrate synthase activity in concordance with earlier studies.

Vascular growth in hypoxic skeletal muscle.

The critical role of skeletal muscle capillaries is the supply of oxygen to skeletal muscle fibers during conditions of maximal aerobic work. The supply of substrates under these conditions is not limited by the vascular bed but rather by the capacity of the sarcolemmal transporter systems. Because of this dominant role of oxygen supply in muscle tissue, hypoxia has generally been considered to be an important stimulus for capillary neo-formation in skeletal muscle. Early morphometric work seemed to indicate that animals exposed to permanent hypoxia had in fact a significantly improved vascular supply in muscle tissue. Later work questioned these early findings and it was concluded that hypoxia per se was not a sufficient stimulus for capillary neo-formation but that additional stimuli such as cold-exposure needed to be present. In humans exposed to severe hypoxia during simulated or real ascents to Mt. Everest an increase in capillary density was in fact found. However, this increase could be shown to result from a reduction of muscle fiber volume and not from capillary growth. Broadly compatible results were obtained in animal experiments in which changes in capillarity were assessed in muscles with limited blood supply which were exposed to chronic electrical stimulation. Recently we have shown that endurance exercise training in humans results in a rise in mRNA of vascular endothelial growth factor (VEGF) only when carried out vigorously and in hypoxia. These results indicate that molecular techniques will allow in the near future to delineate the role played by hypoxia in capillary neo-formation.

Sympathetic neural adaptations to exercise training in humans: insights from microneurography.

Sympathetic nerve activity has long been regarded as an important regulator of blood flow and blood pressure. Its importance has been especially recognized during exercise. The present review examines sympathetic neural adaptations to exercise training in humans obtained by sympathetic nerve recordings to nonactive skeletal muscle. Little evidence exists from both cross-sectional and longitudinal studies indicating that training alters resting muscle sympathetic nerve activity (MSNA). However, MSNA responses during exercise appear to be attenuated after training. This attenuation of MSNA seems to be specific to the trained muscle and not generalizable to other muscle groups. The mechanisms for the decrease in exercise-induced MSNA have been attributed to changes in both the muscle metaboreflex and muscle mechanoreflex. In addition to exercise, training has generally not altered MSNA responses to other stressors such as cold pressor test, lower body negative pressure, and upright tilting. However, the effect of training on baroreflex control of MSNA is equivocal. These conclusions are based on few studies. More comprehensive training studies are needed to better understand the role of training on sympathetic neural outflow.

Exercise, glucose transport, and insulin sensitivity.

Physical exercise can be an important adjunct in the treatment of both non-insulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus. Over the past several years, considerable progress has been made in understanding the molecular basis for these clinically important effects of physical exercise. Similarly to insulin, a single bout of exercise increases the rate of glucose uptake into the contracting skeletal muscles, a process that is regulated by the translocation of GLUT4 glucose transporters to the plasma membrane and transverse tubules. Exercise and insulin utilize different signaling pathways, both of which lead to the activation of glucose transport, which perhaps explains why humans with insulin resistance can increase muscle glucose transport in response to an acute bout of exercise. Exercise training in humans results in numerous beneficial adaptations in skeletal muscles, including an increase in GLUT4 expression. The increase in muscle GLUT4 in trained individuals contributes to an increase in the responsiveness of muscle glucose uptake to insulin, although not all studies show that exercise training in patients with diabetes improves overall glucose control. However, there is now extensive epidemiological evidence demonstrating that long-term regular physical exercise can significantly reduce the risk of developing non-insulin-dependent diabetes mellitus.

Effects of aerobic exercise on ambulatory blood pressure: A meta‐analysis

The purpose of this study was to examine the effect of aerobic exercise on ambulatory systolic and diastolic blood pressure (BP). The results of seven human exercise training studies published in English‐language journals from 1989 to 1993 and representing 12 exercise groups, nine control groups, and a total of 167 subjects were statistically aggregated using the meta‐analytic approach. With outliers deleted from the model, small changes were found among all groups and categories. However, only a change in ambulatory diastolic BP during 24 hours was significantly different from zero. Ambulatory systolic and diastolic BP recorded throughout 24 hours decreased by 1.72 ± 1.80 mmHg (95% confidence interval, 3.10 to 0.34) and 2.56 ± 1.95 mmHg (95% confidence interval, 4.01 to 1.06), respectively. During the waking hours, ambulatory systolic and diastolic BP decreased by 1.25 ± 4.25 mmHg (95% confidence interval, 4.80 to ‐2.30) and 1.32 ± 2.66 mmHg (95% confidence interval, 3.54 to ‐0.90), respectively. A decre...

Effects of weight lifting on resting blood pressure: A meta‐analysis

The purpose of this study was to examine the effect of weight‐lifting exercise on resting systolic and diastolic blood pressure in humans. The results of 10 human exercise training studies published in journals (1966‐1993) and representing a total of 285 subjects (170 exercise, 115 control) were statistically aggregated using the meta‐analytic approach. Across all categories and designs, weight lifting resulted in a small, but statistically significant reduction of ‐3 (p = 0.02) and ‐2 (p = 0.03) mmHg resting systolic and diastolic blood pressure, respectively. This corresponded to a reduction of approximately 2% for both resting systolic and diastolic blood pressure. Neither change was significant for a control group. The results of this study suggest that weight lifting reduces resting systolic and diastolic blood pressure in humans. However, the reduction observed in this study may not be sufficient to recommend weight lifting alone for the purpose of reducing resting blood pressure. A need exists for ...

Exercise-induced cardiac hypertrophy. Fact or fallacy?

After a century of research reports, the notion of exercise-induced cardiac hypertrophy is still an expected adaptation to regular exercise training. Experimental evidence reported both in animals and in humans over the past 3 decades suggests, however, that this conclusion may not be totally warranted. Data from 20 years of echocardiographic investigations of athletes and nonathletes indicate that differences in cardiac dimensions are not very large. Cross-sectional comparisons of over 1000 athletes and roughly 800 control individuals indicate an average difference of 1.6 mm in left ventricular (LV) wall thickness and of 5.3 mm in end-diastolic diameter. Differences reported after training programmes lasting 4 to 52 weeks are even smaller, with average increases of 0.3 mm in LV wall thickness and only 2.1mm in end-diastolic diameter. This article reviews data from animal and human studies concerning cardiac morphology and exercise training to show that the traditional interpretation of the literature has failed to take into account several methodological considerations or factors that may act as confounders in the interpretation of data. Results from animal studies indicate that the observation of cardiac hypertrophy is equivocal at best. In many reports the reported changes in heart size are not significant, and in instances where significant changes are reported these may be seen to be confounded by a number of factors. For example, in rats the reported training-induced hypertrophy may be related to gender differences in the responsiveness of cardiac dimensions or body and/or organ growth rather than to true heart hypertrophy. Furthermore, the interpretation of results from training studies in rats has often been based on the assumption that the metabolic, haemodynamic and thermoregulatory requirements of swimming and running exercise in rats are similar, which may in fact not be the case. In addition, the use of the heart weight/body weight ratio as an index of cardiac hypertrophy, although widespread in animal studies, is open to criticism owing to failure to control for concurrent changes in body weight. Several methodological considerations and factors confounding the outcome of exercise training in humans have also been omitted when interpreting echocardiographic cross-sectional and longitudinal findings. For example, in adult echocardiography the practical resolution of the echocardiographic technique amounts to roughly 2.2mm. It follows, therefore, that unless differences of changes in cardiac dimensions exceed the limit of resolution they are meaningless although statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)