Elite distance runners, ultraendurance athletes, and military personnel routinely complete repeated bouts of prolonged exercise (> 60 min). Repetitive strenuous exercise has been demonstrated to elicit a host of physiological perturbations including cumulative increases in catecholamines (28) and inflammatory cytokines (24) and associated alterations in skeletal muscle morphology. There are limited data, however, documenting the short-term impact of repeated bouts of prolonged exercise on the myocardium.
It is well known that a single bout of prolonged exercise can induce a short-term alteration in left ventricular (LV) function (10,23,32), attributed to a combination of impaired contractility and compliance, as well as shifts in hemodynamic loading (16). Widespread elevations in cardiac biomarkers immediately after an acute bout of prolonged exercise, suggestive of exercise-induced cardiac damage, also have been reported (23,27). Alterations in LV function after an acute bout of prolonged exercise are normally transient, with resumption of normal function typically observed after 24-48 h of recovery (27,32). Similarly, elevated markers of cardiac damage normalize in a comparable time frame (23,26). The temporary nature of these phenomena would suggest that the impact of a single bout of endurance exercise on exercise capacity and health is minimal, with the extent of the decline in LV function rarely matching the levels usually observed clinically (3).
It is possible, however, that the physiological stress placed on the myocardium during repeated bouts of prolonged exercise may result in a cumulative decrement in cardiac function and/or exercise-induced cardiac damage, subsequently delaying the recovery process. Accordingly, this may have important implications for both health and functional capacity. The limited number of investigations that have attempted to examine the impact of repeated bouts of activity on the heart have been restricted to measurement of cardiac biomarkers without the assessment of cardiac function (2,13). Further, the limited experimental designs previously employed have prevented the examination of the time course of biomarker release. The only authors that have examined both cardiac function and cardiac damage during a repeated-bout protocol were unable to collect echocardiographic and biochemical data in the same cohort (26).
The aim of the present study was to examine the impact of 3 d of prolonged hill running on both LV function and markers of cardiac damage to determine whether a cumulative effect would be apparent. We hypothesized that repeated bouts of prolonged exercise would result in a progressive decrement in cardiac function and accumulation of circulating cardiac biomarkers.
Subjects and Study Design
Ten highly trained long-distance male runners (mean ± SD; age: 33 ± 7 yr; height: 1.77 ± 0.06 m; body mass: 70.4 ± 8.5 kg; V˙O2max: 63.0 ± 5.2 mL·kg−1·min−1) who were undertaking five or more endurance training sessions per week at the time of data collection volunteered and provided written informed consent to take part in the study. Ethical approval for the study was granted by Brunel University ethics committee before data collection. Participants reported no personal or early family history of cardiopulmonary disease.
The exercise protocol comprised a three-lap, 15.3-mile run over mountainous terrain (total elevation: 3717 ft) each day for three consecutive days. A subset of six participants completed a further exercise bout on the fourth day. The exercise protocol and testing procedures were undertaken at the same time and location on each day. Participants were allowed to drink ad libitum during the run, with frequent water stations situated at various points on the route. Carbohydrate gels were also consumed freely throughout the exercise period. Environmental conditions remained relatively stable throughout the testing period (mean ± SD; temperature: 13.0 ± 2.7°C; humidity: 63 ± 11%).
The study employed a repeated-measures design, with assessment procedures taking place before each exercise bout, immediately after exercise (within 15 min), and 1 h after exercise. The preexercise procedures before bouts 2-4 were conducted approximately 20 h after the previous exercise bout, serving as the recovery assessment from the preceding day. Identical echocardiographic and venous blood-sampling procedures were conducted at each assessment, excluding the 1-h postexercise assessment, where only blood was drawn. Body mass was also measured before, after, and 20 h after the race. Heart rates during each exercise bout were measured via a Polar heart rate monitor (Polar Team System, Polar Electro Oy, Finland) and downloaded using Polar Precision Performance software (v. 3.0). Before the testing session, each participant underwent a maximal exercise Bruce treadmill protocol to determine V˙O2max following BASES guidelines (1).
Each participant underwent a resting echocardiographic examination in the left lateral decubitas position. A single experienced sonographer performed all measurements with a commercially available ultrasound system (Esaote Megas GPX, Imotek, Italy), using a 2.5- to 4-MHz phased array transducer. All acquisitions were performed at end expiration, and the standard measurements were conducted in accordance with American Society of Echocardiography guidelines (25). Images were stored and analyzed offline at a later date, with an average of three to five consecutive cardiac cycles taken for the calculation of all echocardiographic measurements. At the time of the echocardiographic assessment, resting heart rate was recorded via an integrated three-lead ECG, and blood pressure was determined using standard auscultation procedures.
Two-dimensionally guided M-mode images from a parasternal long-axis view were recorded for measurement of LV internal diameter during diastole and systole (LVIDd and LVIDs, respectively) and left ventricular posterior wall thickness during systole. Left ventricular meridional wall stress (LVMWS) was calculated from the M-mode and systolic blood pressure data (21) and was employed as a surrogate of afterload, whereas LVIDd was used as an estimation of preload. The modified biplane Simpson's method was employed in the calculation of ejection fraction and systolic blood pressure/end systolic volume (SBP/ESV) ratio, using two-dimensional cineloops obtained from apical four- and two-chamber views (25).
Diastolic filling was examined using pulsed-wave Doppler interrogation of mitral valve inflow velocities. An apical four-chamber view was obtained, with care taken to maximize the diameter of the mitral valve annulus, and a sample volume cursor was placed parallel to the flow at the level of the mitral annulus. Minor transducer adjustments were made to obtain optimal spectral display (highest velocity with least spectral dispersion). The Doppler velocity curves were digitized to obtain peak early filling (E waves, cm−1) and peak late filling (A wave, cm−1), allowing calculation of early to late diastolic filling ratio (E:A).
The flow propagation velocity (Vp) of the LV was assessed as an adjunct to pulsed-wave Doppler. A color M-mode was recorded from an apical four-chamber view, with the M-mode sample line placed along the plane from the apex to the tips of the mitral valve leaflets. Color Doppler was used with optimal gain for minimal background noise, and the pulse repetition frequency was reduced to provide a nyquist velocity of 40-60 cm·s−1. A slope caliper was drawn from the mitral valve at the first aliasing velocity during early filling to 4 cm distally into the LV cavity to obtain the Vp. Additionally, the E:Vp ratio was calculated and employed as a surrogate of early left atrial pressure. Coefficient-of-variation data for echocardiographic measurements reported previously for our group range from 2.7 to 5.4% (9).
A 5-mL whole-blood sample was drawn from an antecubital vein on each occasion, which was left to clot and then centrifuged, with the serum drawn off and stored (−80°C) for subsequent analysis of N-terminal pro-BNP (proBNP) and cardiac troponin T (cTnT). The proBNP concentrations were determined with an Elecsys proBNP ECLIA on the Roche Elecsys 1010 (Roche Diagnostics, Lewes, Sussex), with an analytical range of 5-35,000 ng·L−1 and intraassay and interassay imprecision of 0.7-1.6 and 5.3-6.6%, respectively (5). Cardiac troponin T was analyzed using the third-generation TROP T STAT assay by electrochemiluminescent immunoassay (ECLIA) technology, employed within the Elecsys 1010 automated batch analyzer (Roche Diagnostics, Lewes, Sussex). Assay imprecision was 5.5% at 0.32 μg·L−1 and 5.4% at 6 μg·L−1, with a detection limit of 0.01 μg·L−1. Values exceeding the assay's detection limit of 0.01 are considered to represent myocardial damage (6).
All pre- and postexercise echocardiographic variables were analyzed using a repeated-measures ANOVA using pairwise comparisons with a Bonferroni correction. Paired-samples t-tests were used to analyze the 20-h post-bout 3 data and the complete bout 4 dataset because of the smaller sample size. A repeated-measures ANOVA was also employed in the analysis of pre-, post-, 1-h post-, and 20-h postexercise proBNP levels. Cardiac troponin T was analyzed descriptively because of the likelihood of undetectable prerace values. Correlations between delta pre-post values for each variable were determined via Pearson's product-moment correlation analysis, with the r 2 value employed in the calculation of the percentage of shared variance. Cardiac function variables were also correlated to loading indices. All analyses were performed using SPSS (SPSS v11.5 for Windows, SPSS Inc, IL), with alpha set at 0.05. Data are reported as mean ± SD.
All 10 participants completed the three exercise bouts, with 20-h post-bout 3 data collected on all but one athlete. A subset of six athletes also completed a fourth exercise bout on the next consecutive day. The mean values for finish time, in-exercise heart rate, and body mass loss during the four exercise bouts were (mean ± SD) 139.9 ± 2.1 min, 155 ± 8 bpm, and 1.4 ± 0.3 kg, respectively, with no significant difference in these parameters between each bout (Table 1).
Left ventricular (LV) systolic function, as assessed by ejection fraction (EF) and systolic blood pressure/end-systolic volume (SBP/ESV), did not show any significant pre-post differences for any exercise bout (Fig. 1). Ejection fraction, however, demonstrated a cumulative decrement during the exercise protocol, with a statistically significant (P = 0.027) reduction compared with baseline values after the third exercise bout (mean ± SD: 56.3 ± 4.4 vs 51.3 ± 5.9%, Fig. 1). For clarity, individual data for the cumulative decrement in EF are presented in Figure 2. After 20 h of recovery from the third exercise bout, EF only increased to 53.9 ± 4.0%, which was still significantly (P = 0.042) lower than baseline. Ejection fraction remained depressed in the subset immediately after the fourth exercise bout (53.3 ± 6.9%).
The E:A ratio was significantly reduced after bout 1 (mean ± SD: 1.9 ± 0.5 vs 1.4 ± 0.3, P = 0.003) and after bout 3 (2.0 ± 0.5 vs 1.3 ± 0.4, P = 0.006) compared with the respective prebout values (Fig. 3). However, the 34% decrease in E:A pre- to post-bout 2 was not significant. Although E:A demonstrated a significant (P < 0.05) reduction after each exercise bout compared with baseline, the ratio consistently increased after each 20-h recovery period, indicating a noncumulative pattern of change. Although interindividual differences were apparent in absolute changes in E:A, Figure 4 highlights the consistency of change in E:A across time in individual subjects. The time course of the alterations in E:A after each bout were not observed in Vp values (Fig. 3), which did not alter significantly pre- to postexercise at any point throughout the protocol. A significant (P = 0.007) reduction in E:A of a similar magnitude to the previous exercise bouts was also observed in the subset that completed a fourth bout.
The changes in resting heart rate throughout the exercise protocol were not significantly (P > 0.05) different (Table 2) or related to any of the changes in E:A. The increase in heart rate after the third exercise bout, however, was significantly related to the alterations in EF (Table 3). Preload, as assessed by LV internal diameter during diastole (LVIDd), did not change significantly pre- to postexercise for each bout (Table 2) and was not related to any of the observed functional changes. Further, the E:Vp ratio, employed as a surrogate of left atrial pressure, did not differ significantly between bouts (Table 2). In contrast, systolic blood pressure (SBP) showed a significant decrease after bouts 2 and 3 compared with baseline values (P = 0.046 and 0.027, respectively, Table 2). The change in SBP was related to the individual differences in SBP/ESV after bout 3 (Table 3), yet this is not an unexpected finding because this functional parameter is partially derived from SBP.
Elevations in proBNP were apparent after each exercise bout (mean percentage increase from baseline: 81, 238, and 241% for bouts 1, 2, and 3, respectively, Fig. 5). These postexercise changes were not significant (P > 0.05) because of large variation within the sample, where the smallest and largest pre-post changes in proBNP across the exercise protocol were 10.1 and 104.4 ng·L−1, respectively.
Similarly, a noncumulative pattern of cTnT release was observed throughout the protocol. One athlete exhibited an elevated cTnT of 0.079 μg·L−1 immediately after the first exercise bout. This individual, together with three other individuals, also demonstrated cTnT elevations 1 h after bout 1 (range: 0.013-0.125 μg·L−1), which had returned to undetectable levels in all athletes after 20 h of recovery. No subsequent cTnT elevations were observed after bouts 2 or 3, apart from the initial individual who demonstrated continually elevated cTnT at each assessment after bout 2 and before and after bout 3 (range: 0.038-0.135 μg·L−1), which only returned to undetectable levels after 20 h of recovery from bout 3. From the subset of athletes who completed a fourth bout, only one isolated cTnT elevation was observed (0.013 μg·L−1). This athlete had not demonstrated elevated cTnT levels in any of the previous bouts.
The present findings reveal distinctly different patterns of altered LV systolic and diastolic function in response to the repeated-bout protocol. The reduction in EF noted after the third bout might be suggestive of a cumulative postexercise decrement in LV systolic function, although the observed changes are small and, thus, unlikely to be of clinical importance. The slightly elevated preexercise EF value on day 3 compared with before bouts 1 and 2 may represent artifacts of day-to-day variability or measurement error, thus explaining the observed reduction in EF after bout 3. Yet, a 13% decrease in EF after bout 3 compared with baseline is greater than would be expected from measurement variability, and therefore some discussion on this finding is warranted. A similar depression in EF and/or SBP/ESV after a single bout of prolonged exercise has been reported previously (18,26), although these reductions have typically been observed after exercise periods of more than 6 h. As such, it has been postulated that a duration-dependent threshold may exist for exercise-induced alterations in systolic function (27,32). This theory is reinforced by consistent reports of unaltered systolic function after shorter exercise durations (10,11).
Despite the moderate duration of each exercise bout in the present study, the repetitive nature of the protocol, in combination with limited recovery, may account for the observed depression in systolic function. A depression in systolic function persisted within the subset of participants who completed a fourth bout, lending further support to the notion of a cumulative influence. The cumulative impact also may have modified the typical recovery time course of the observed alterations in systolic function. In contrast to previous reports of a return of normal systolic function after 24 h of recovery (27,32), EF and SBP/ESV in the present study remained depressed 20 h after exercise cessation after the third exercise bout. The subset of athletes who completed a fourth exercise bout also exhibited no improvement in EF after 20 h of recovery. Time constraints prevented further monitoring of left ventricular function, and therefore it was not possible to determine the time point at which EF returned to baseline. The clinical implications of the sustained reduction in LV systolic function are yet to be elucidated; however, it is important to note that EF did not drop below the lower limit for normal LV systolic function (50%) (29), suggesting that the clinical impact is likely negligible. Further, the alterations in EF did not seem to impact exercise performance in the current protocol, evidenced by similar finish times and exercise heart rates across the exercise bouts.
An increase in postexercise resting heart rate after bout 3 was related to the decrement in EF, yet this can only explain 48% of the change, according to the percentage of shared variance calculated from the r 2 correlation coefficient data. Further, there was no significant relationship between changes in EF and changes in loading. Taken together, the present findings suggest that an impairment of LV inotropic properties may contribute to the observed alterations in systolic function. Additionally, a mean difference of 10 bpm in exercise heart rate between the first and third bouts, despite relatively little change in the mean completion times, may represent a depression in LV chronotropic function in addition to the change in inotropy evidenced through echocardiography. Reports of a gradual decline in heart rate during single and repeated bouts of prolonged endurance exercise (14) have previously been attributed to plasma volume expansion (8), yet in the present study, a maintained LVIDd and E:Vp ratio throughout the exercise protocol suggests that plasma volume was not altered. Alternatively, the exercise-induced changes in both chronotropic and inotropic properties of the LV observed in the present and previous studies may be explained by an accumulation of circulating catecholamines during repeated bouts of endurance exercise (29) and a subsequent downregulation of beta-adrenergic receptors (30).
Within the present study, parameters of diastolic filling exhibited the typical pattern of change (27) in response to each single bout of prolonged exercise. Compared with systolic function, however, the acute changes in diastolic filling were not cumulative, with a rapid normalization of diastolic filling within each 20-h recovery period. The observed decrease in diastolic filling after bouts 1 and 2, in the absence of changes in systolic function, is in agreement with the aforementioned duration-dependent theory, whereby changes in diastolic filling precede changes in systolic function (7). In contrast to the onset of altered systolic function, decreases in diastolic filling have been documented after exercise durations of 60 min and above (27,32). The E:A ratio was significantly reduced by 27, 32, and 32% after exercise bouts 1, 2, and 3, respectively, compared with baseline, indicating altered diastolic filling. This change exceeds variability in measurement error, indicating a substantial postexercise reduction in E:A that approached the clinical cutoff for diastolic dysfunction of less than 1.0 (17). The observed decrease in E:A was accompanied by a similar decline in Vp that was nonsignificant. Although the acute alterations in E:A were significant, they did not seem to have an impact on subsequent exercise performance, as demonstrated by similar finish times for each bout.
It is likely that because of the athletes' experience participating in prolonged exercise events, appropriate rehydration and refueling strategies were employed before, during, and after each exercise bout, explaining the minimal impact on preload and the athletes' ability to maintain stable body mass throughout the course of the study. Moreover, the nonsignificant changes in preload, as demonstrated by the lack of change in E:Vp ratio, were unrelated to the alterations in LV function observed in the present and previous studies (10,27). Because changes in loading cannot fully explain the decrement in E:A, it is likely that an intrinsic impairment in LV relaxation and/or compliance may contribute to the altered diastolic filling dynamics. A lack of difference between baseline values before each exercise bout suggests that normal diastolic filling resumed after each 20-h recovery period. This finding is in agreement with previous literature (27,32), yet it does not follow the same time course observed with the present systolic data. Separate recovery patterns may imply that different mechanisms underpin exercise-induced alterations in LV systolic and diastolic function. Future research in this area should further investigate the contribution of possible mechanisms underpinning this phenomenon.
Concomitant to the cumulative reduction in LV systolic function, a trend towards a progressive increase in proBNP during each successive exercise bout was apparent, yet this did not reach statistical significance, likely because of a high interindividual variability in proBNP levels. Although not statistically significant in the present study, elevations in proBNP after an acute bout of prolonged exercise have been previously documented (19) and may be attributed to increased myocardial wall stress during the exercise period (15). B-type natriuretic peptide is currently employed as a marker of LV dysfunction within a clinical setting (20,22); however, pre- to postexercise proBNP levels were not correlated with pre- to postexercise LV systolic function parameters in the present study. Further, the present proBNP levels did not exceed the clinical cutoff of 125 ng·L−1 typically observed for congestive heart failure patients (12) at any point during the exercise protocol. Accordingly, the postexercise proBNP levels measured in the present investigation are likely of minimal clinical significance.
In contrast to proBNP, cTnT demonstrated postexercise elevations compared with baseline after bout 1. The transient elevations in cTnT observed in four individuals (40%) after the first exercise bout, unrelated to age or training status, are comparable with the proportion of cTnT elevations reported in runners on completion of a marathon (31). Apart from an isolated case of elevated cTnT throughout the protocol, the increases in troponin after bout 1 were not replicated in subsequent bouts, with only one athlete from the subset demonstrating elevated cTnT after the fourth bout. One explanation for the absence of cTnT release after bouts 2 and 3 may be that the exercise stress was not of a sufficient intensity to elicit further troponin release. Yet, similar finish times between each bout suggest that the exercise intensity was maintained throughout the course of the study, and therefore a reduction in exercise intensity is unlikely to explain the inconsistent cTnT release. Alternatively, the observed troponin release kinetics may reflect a cardioprotective response to prolonged exercise, whereby the initial exercise stimulus may have elicited adaptations to prevent further myocyte damage and cTnT release. The cellular and morphological adaptations of skeletal muscle in response to acute endurance exercise are well documented, and the preconditioning effect may be replicated within cardiac myocytes (4). Future investigators in this area should attempt to examine the possible link between cardioprotective adaptations and sporadic troponin release within an athletic population.
In summary, different responses in the kinetics of altered LV systolic and diastolic function were observed after repeated bouts of prolonged exercise. Left ventricular systolic function was significantly reduced after the third bout compared with baseline, although the observed changes were negligible in comparison with clinical levels of LV dysfunction. Further, these changes did not impact exercise performance throughout the protocol, as evidenced by similar exercise heart rates and finish times during each bout. In contrast to the cumulative decrease in systolic function, LV diastolic filling exhibited consistent noncumulative reductions after each bout. Altered LV diastolic function was unrelated to changes in loading, potentially indicating an intrinsic impairment of LV-relaxation properties. Release of cTnT also did not demonstrate a cumulative pattern, with sporadic elevations after the first bout but no further release of troponin thereafter, except for in one subject. This may be suggestive of a cardioprotective adaptation elicited by the first bout of exercise, yet the clinical ramifications of cTnT release after exercise remain to be elucidated. Exercise performance did not seem to deteriorate throughout the protocol in the presence of alterations in LV function and elevated cTnT; however, the exercise protocol employed was of a limited duration and may not be representative of longer, multistage, ultraendurance events. Future work in this area should investigate the potential impact of these functional and biochemical alterations on exercise capacity in athletes who are required to perform optimally each day with limited recovery time, and in military personnel who regularly undertake intensive, repeated bouts of prolonged exercise.
1. Bird, S., and R. Davidson (Eds.). BASES Physiological Testing Guidelines.
3rd ed. Leeds, UK, The British Association for Sport and Exercise Sciences (BASES), pp. 64-65, 1997.
2. Bonetti, A., F. Tirelli, R. Albertini, C. Monica, M. Monica, and G. Tredici. Serum cardiac troponin T
after repeated endurance exercise events. Int. J. Sports Med.
3. Bruch, C., M. Gotzmann, J. Stypmann, et al. Electrocardiography and Doppler echocardiography
for risk stratification in patients with chronic heart failure: incremental prognostic value of QRS duration and a restrictive mitral filling pattern. J. Am. Coll. Cardiol.
4. Chen, Y., R. Serfass, S. Mackey-Bojack, K. Kelly, J. Titus, and F. Apple. Cardiac troponin T
alterations in myocardium and serum of rats after stressful, prolonged intense exercise. J. Appl. Physiol.
5. Collinson, P. O., S. C. Barnes, D. C. Gaze, G. Galasko, A. Lahiri, and R. Senior. Analytical performance of the N terminal pro B type natriuretic peptide (NT-proBNP) assay on the Elecsys 1010 and 2010 analysers. Eur. J. Heart Failure
6. Collinson, P. O., F. G. D. Boa, and D. C. Gaze. Measurement of cardiac troponins. Ann. Clin. Biochem.
7. Dawson, E., K. George, R. Shave, G. Whyte, and D. Ball. Does the human heart fatigue subsequent to prolonged exercise? Sports Med.
8. Fellmann, N., P. Ritz, J. Ribeyre, B. Beaufrere, M. Delaitre, and J. Coudert. Intracellular hyperhydration induced by a 7-day endurance race. Eur. J. Appl. Occup. Physiol.
9. George, K., G. Whyte, C. Stephenson, et al. Postexercise left ventricular function and cTnT in recreational marathon runners. Med. Sci. Sports Exerc.
10. George, K., D. Oxborough, J. Forster, et al. Mitral annular myocardial velocity assessment of segmental left ventricular diastolic function after prolonged exercise in humans. J. Physiol.
11. Goodman, J. M., P. R. McLaughlin, and P. P. Liu. Left ventricular performance during prolonged exercise: absence of systolic dysfunction. Clin. Sci.
12. Gustafsson, F., F. Steensgaard-Hansen, J. Badskjaer, A. H. Poulsen, P. Corell, and P. Hildebrandt. Diagnostic and prognostic performance of N-terminal proBNP in primary care patients with suspected heart failure. J. Card. Fail.
13. Konig, D., Y. O. Schumacher, L. Heinrich, A. Schmid, A. Berg, and H. H. Dickhuth. Myocardial stress after competitive exercise in professional road cyclists. Med. Sci. Sports Exerc.
14. Laursen, P., and E. Rhodes. Factors affecting performance in an ultra endurance triathlon. Sports Med.
15. McCullough, P. A., T. Omland, and A. S. Maisel. B-type natriuretic peptides: a diagnostic breakthrough for clinicians. Rev. Cardiovasc. Med.
16. Middleton, N., R. Shave, K. George, G. Atkinson, G. Whyte, and E. Hart. Left ventricular function following prolonged exercise: a meta-analysis. Med. Sci. Sport Exerc.
17. Mottram, P. M., L. Short, T. Baglin, and T. Marwick. Is 'diastolic heart failure' a diagnosis of exclusion? Echocardiographic parameters of diastolic dysfunction in patients with heart failure and normal systolic function. Heart Lung Circ.
18. Niemela, K. O., I. J. Palatsi, M. J. Ikaheimo, J. T. Takkunen, and J. J. Vuori. Evidence of impaired left ventricular performance after an uninterrupted competitive 24 hour run. Circulation
19. Niessner, A., S. Ziegler, J. Slany, E. Billensteiner, W. Woloszczuk, and G. Geyer. Increases in plasma levels of atrial and brain natriuretic peptides after running a marathon: are their effects partly counterbalanced by adrenocortical steroids? Eur. J. Endocrinol.
20. Omland, T., and C. Hall. N-terminal pro-B-type natriuetic peptide. In: Cardiac Markers,
A. H. B. Wu (Ed.). Totowa, NJ: Humana Press Inc, pp. 411-427, 2003.
21. Reichek, N., J. Wilson, M. St John Sutton, T. A. Plappert, S.Goldberg, and J. W. Hirshfeld. Noninvasive determination of left ventricular end-systolic stress: validation of the method and initial application. Circulation
22. Richards, A. M., G. Nicholls, E. A. Espiner, et al. B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation
23. Rifai, N., P. S. Douglas, M. O'Toole, E. Rimm, and G. S. Ginsburg. Cardiac troponin T
and I, echocardiographic [correction of electrocardiographic] wall motion analyses, and ejection fractions in athletes participating in the Hawaii Ironman Triathlon. Am. J. Cardiol.
24. Ronsen, O., T. Lea, R. Bahr, and B. Pedersen. Enhanced plasma IL-6 and IL-1ra responses to repeated vs. single bouts of prolonged cycling in elite athletes. J. Appl. Physiol.
25. Schiller, N. B., P. M. Shah, M. Crawford, et al. Recommendations for quantification of the left ventricle by two-dimensional echocardiography
. American Society of Echocardiography
Committee on Standards, Subcommittee on Quantification of Two-Dimensional Echocardiograms. J. Am. Soc. Echocardiogr.
26. Shave, R. E., E. Dawson, G. Whyte, et al. Evidence of exercise-induced cardiac dysfunction and elevated cTnT in separate cohorts competing in an ultra-endurance mountain marathon race. Int. J. Sports Med.
27. Shave, R., E. Dawson, G. Whyte, K. George, D. Gaze, and P.Collinson. Altered cardiac function and minimal cardiac damage during prolonged exercise. Med. Sci. Sports Exerc.
28. Stich, V., I. de Glisezinski, M. Berlan, et al. Adipose tissue lipolysis is increased during a repeated bout of aerobic exercise. J. Appl. Physiol.
29. Varela-Roman, A., L. Grigorian, E. Barge, P. Bassante, M. G. de la Pena, and J. R. Gonzalez-Juanatey. Heart failure in patients with preserved and deteriorated left ventricular ejection fraction. Heart
30. Welsh, R., D. Warburton, D. Humen, D. Taylor, J. McGavock, and M. McGavock. Prolonged strenuous exercise alters the cardiovascular response to dobutamine stimulation. J. Physiol.
31. Whyte, G., K. George, R. Shave, et al. Impact of marathon running on cardiac structure and function in recreational runners. Clin. Sci. (Lond.)
32. Whyte, G. P., K. George, S. Sharma, et al. Cardiac fatigue following prolonged endurance exercise of differing distances. Med. Sci. Sports Exerc.
Keywords:©2007The American College of Sports Medicine
REPETITIVE EXERCISE; ECHOCARDIOGRAPHY; CARDIAC TROPONIN T; B-TYPE NATRIURETIC PEPTIDE