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J Appl Physiol 102: 681-687, 2007. First published November 2, 2006; doi:10.1152/japplphysiol.00641.2006
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Sex differences in left ventricular function and beta-receptor responsiveness following prolonged strenuous exercise

Jessica M. Scott,1 Ben T. A. Esch,1 Mark J. Haykowsky,3 Saul Isserow,2 Michael S. Koehle,2 Bevan G. Hughes,2 Dominik Zbogar,1 Shannon S. D. Bredin,1 Don C. McKenzie,2 and Darren E. R. Warburton1

1Cardiovascular Physiology and Rehabilitation Laboratory, and 2Faculty of Medicine, University of British Columbia, Vancouver, British Columbia; and 3Cardiovascular Therapeutic Exercise Laboratory, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada

Submitted 7 June 2006 ; accepted in final form 26 October 2006


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Sex differences in neuroendocrine and metabolic responses to prolonged strenuous exercise (PSE) have been well documented. The aim of this investigation was to examine sex differences in left ventricular function and cardiac beta-receptor responsiveness following a single bout of PSE. Nine male and eight female triathletes were examined during three separate sessions: before, immediately after, and 24 h following a half-ironman triathlon using dobutamine stress echocardiography. Steady-state graded infusions of dobutamine were used to assess beta-receptor responsiveness. Slopes calculated from linear regressions between dobutamine doses and changes in heart rate and contractility for each participant were used as an index of beta-receptor responsiveness. Despite no change in preload, fractional area change decreased from baseline after the race in both men and women, with a greater decrease in men [men: 54.1% (SD 2.1) to 50.7% (SD 3.4) vs. women: 55.4% (SD 2.7) to 53.3% (SD 2.5); P < 0.05]. The amount of dobutamine necessary to increase heart rate by 25 beats/min [men: 29.6 µg·kg–1·min–1 (SD 6.6) to 42.7 µg·kg–1·min–1 (SD 12.9) vs. women: 23.5 µg·kg–1·min–1 (SD 4.0) to 30.0 µg·kg–1·min–1 (SD 7.8); P < 0.05] and contractility by 10 mmHg/cm2 [men: 20.9 µg·kg–1·min–1 (SD 5.1) to 37.0 µg·kg–1·min–1 (SD 11.5) vs. women: 22.6 µg·kg–1·min–1 (SD 6.4) to 30.7 µg·kg–1·min–1 (SD 7.2); P < 0.05] was greater in both men and women postrace. However, the amount of dobutamine required to induce these changes was greater in men, reflecting larger beta-receptor alterations in male triathletes following PSE relative to women. These data suggest that following an acute bout of PSE, male triathletes demonstrate an attenuated chronotropic and inotropic response to beta-adrenergic stimulation compared with female triathletes.

beta-adrenergic receptor; contractility; dobutamine stress; half-ironman triathlon

DESPITE AN ACCUMULATION OF evidence suggesting that prolonged strenuous exercise (PSE) is associated with decreased left ventricular (LV) performance, the precise mechanism responsible for this phenomenon has not been fully elucidated (13). Results from recent investigations have suggested that decreases in LV systolic function following exercise, also referred to as cardiac fatigue, may be partially caused by alterations in cardiac beta-receptor function (23, 39, 51). Although several studies have examined LV performance following PSE in men (15, 35, 39, 43, 50), few have examined the occurrence of cardiac fatigue in female athletes. Given that significant sex differences exist in response to acute exercise (6, 12), it is also likely that LV function following PSE differs between men and women.

Several investigations have demonstrated that significant sexual dimorphisms exist in neuroendocrine and metabolic responses (12). In response to exercise, men may have not only increased catecholamine responses but also enhanced cardiovascular parameters such as higher systolic and mean arterial pressure (12). Noninvasive measures of autonomic neural control of heart rate using heart rate variability (HRV) have indicated that women have greater parasympathetic and less sympathetic control of heart rate than men (6). These results suggest that with higher levels of catecholamines generated during exercise, men may experience greater catecholamine-induced reductions in beta-receptor responsiveness, and consequently, greater decreases in LV function following PSE relative to women. Despite an accumulation of evidence that cardiac function is impaired in male athletes during PSE (51), no information exists regarding sex differences in beta-receptor responsiveness and its impact on cardiovascular performance during PSE.

During extended periods of exercise, circulating levels of catecholamines are dramatically increased (44). Prolonged exposure of beta-receptor cells to high concentrations of catecholamines may lead to a decreased hormonal sensitivity (28). This has been demonstrated experimentally in dogs, where exercise was shown to result in catecholamine-mediated cardiac beta-receptor desensitization (19). Such desensitization of cardiac receptors is one of the common symptoms associated with chronic heart failure, a condition characterized by chronically elevated levels of catecholamines (5). With high levels of circulating catecholamine levels during exercise, it is plausible that similar alterations in beta-receptor responsiveness will occur in the healthy human heart. Accordingly, the purpose of this investigation was to evaluate the consequences of PSE on LV function and beta-receptor responsiveness in healthy men and women. We hypothesized that 1) as a result of PSE, men would have larger reductions in cardiac beta-receptor responsiveness and LV systolic function relative to women and 2) the changes in systolic function following PSE would be related to alterations in beta-receptors responsiveness.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
Participants.   Nine male and eight female endurance-trained triathletes were recruited. The participants who volunteered for this investigation were exceptionally well conditioned male and female amateur athletes. Briefly, the athletes trained 14.2 h/wk (SD 1.7) [men: 15.0 h/wk (SD 0.6); women: 14.2 h/wk (SD 1.4)], exercised regularly 5–7 days/wk for a minimum of 2 yr, and competed in athletic events on a regular basis. All participants were free of cardiovascular disease. Participant characteristics are shown in Table 1. The experimental protocol was approved by the Clinical Research Ethics Board of the University of British Columbia, and all participants provided their written informed consent to participate in this study.


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  		Table 1. Selected physiological variables in male and female triathletes

 
General protocol.   Participants underwent four separate testing days: 1) familiarization and assessment of maximal oxygen consumption (VO2 max), 2) dobutamine stress echocardiography 6 days before PSE (Pre), 3) dobutamine stress echocardiography immediately following PSE (Post), and 4) dobutamine stress echocardiography 24 h following PSE (Rec). Participants were instructed to refrain from exercise and abstain from caffeine and other autonomic stimulants such as prescription and nonprescription drugs for at least 48 h before each experimental protocol. Lean body mass was determined using a bioelectrical impedance scale (model TBF300A, Tanita, Sindelfingen, Germany).

Maximal exercise.   During the first session, VO2 max, and maximum heart rate were determined with a graded maximal cycle ergometer test. After a standardized 5 min warm-up period, workload increased by 30 W every minute, during which time ventilatory parameters were acquired using a metabolic cart (model Max-1, PhysioDyne, Quogue, NY). The following criteria were used for determining VO2 max: 1) no further increase in oxygen consumption despite an increase in exercise intensity and 2) volitional exhaustion.

Nonexercise conditions.   During Pre and Rec sessions, two-dimensional and Doppler echocardiography were performed while participants rested supine for 10 min. Continuous incremental infusions of dobutamine were then administered intravenously (see Assessment of beta-receptor responsiveness below).

Prolonged strenuous exercise.   During the Post session, all athletes completed a half-ironman triathlon race involving a continuous 1.5-km swim, 90-km cycle, and 21.1-km run. The racing event was conducted during a sunny day (temperature 13°C, precipitation 0 mm, and wind speed 12 km/h). Athletes were encouraged to consume fluid ad libitum during the race, and data were collected on average 30 min after race completion in all participants. Body mass was measured during the Pre, Post, and Rec sessions.

Assessment of beta-receptor responsiveness.   During the Pre, Post, and Rec sessions participants underwent a dobutamine stress test. After acquisition of baseline resting echocardiographic images, infusion of the beta-receptor agonist dobutamine was commenced where incremental doses of the drug (0, 5, 10, 20, 30, and 40 µg·kg–1·min–1) were administered every 3 min. Continuous heart rate was measured from an electrocardiogram, and beat-by-beat changes (corrected each minute) in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured noninvasively (Finapres, Ohmeda). Average heart rate, SBP, DBP, and MAP were calculated offline for the last 2 min of each stage. Linear regression relationships were constructed relating the increase in heart rate and contractility to the dose of dobutamine. As previously described (10, 11, 18, 25, 45), the slopes describing the linear stimulus-response relationship between the dose of dobutamine vs. heart rate and contractility provided a measure of the responsiveness of cardiac beta-receptors.

Echocardiography.   Two-dimensional and Doppler echocardiography were performed during all beta-receptor sensitivity assessments. Left ventricular two-dimensional images were obtained by a single, experienced clinical sonographer in the long-axis, short-axis (midpapillary muscles), and apical two- and four-chamber views according to the American Society of Echocardiography guidelines (42). All echocardiography data were analyzed by a single trained observer following the experiment, and a minimum of three cardiac cycles were averaged for analysis. LV systolic function was evaluated using fractional area change, end-systolic meridional wall stress, and myocardial contractility (SBP/end-systolic cavity area) (24). Pulsed Doppler recordings were employed to assess diastolic filling; in particular, early (E) and atrial (A) peak velocities were measured, and the ratio of early to late diastolic filling (E/A) was calculated.

Assessment of cardiac autonomic modulation.   To provide an indication of autonomic modulation Pre, Post, and Rec, HRV was assessed in eight participants (4 men and 4 women) during 10 min of supine rest (i.e., dobutamine dosage 0 µg·kg–1·min–1). Heart rate variability was sampled at 1,000 samples/s with an analog-to-digital converter (ADInstruments) from ECG to computer. The ECG segment was then evaluated according to previously established guidelines (47). Both frequency domain and time domain measures were analyzed. To assess frequency domain measures, the power spectra were estimated using a 1,024-point linear fast Fourier transform algorithm. The power spectra were then analyzed for total (0.0–0.4 Hz), low-frequency (LF; 0.04–0.15 Hz), and high-frequency (HF; 0.15–0.4 Hz) power. HF power is almost entirely mediated by the vagal activity in the sinoatrial node (2, 39, 52), whereas LF power reflects the mixed modulation of vagal and sympathetic activities (1). Recently, Goldberger and colleagues (21) reported that certain time domain parameters [square root of the mean of squared differences between successive intervals (RMSSD)] provide a strong index of parasympathetic reactivation in the recovery period following exercise. We therefore also evaluated the R-R interval time series automatically obtained from the raw signals. From the R-R data, the RMSSD was also computed.

Statistical analysis.   Differences between echo-Doppler measures of LV function, differences between dobutamine responses at rest and after prolonged exercise, gender differences, and HRV parameters were examined using repeated-measures analysis of variance with Tukey post hoc comparisons. Differences in slopes, y-intercepts and x-intercepts between Pre, Post, and Rec conditions were compared by analyzing the least squares linear estimates generated by each participant. The level of significance was set a priori at P < 0.05. Data are presented as means (SD) at Pre, Post, and Rec.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
PSE.   All athletes successfully completed the half-ironman triathlon with average finishing times of 4 h 45 min (SD 15) for men and 5 h 16 min (SD 21) for women. Participants completed the race at an average intensity equivalent to 80.3% (SD 12) of their maximal heart rate. There were no differences between men and women in exercise intensity. Because of the staggered pool start, athletes finished the half-ironman at various times throughout the day, and they were assessed within 30 min of cessation of exercise.

Echocardiography.   There were no differences between men and women for end-systolic cavity dimension, contractility, fractional area change, and wall stress at resting baseline (i.e., dobutamine dosage 0 µg·kg–1·min–1) Pre. However, men had significantly greater end-diastolic cavity dimension and E/A ratio[men: 2.10 (SD 1.5) vs. women: 1.83 (SD 0.8)] relative to women. At race finish (Post), diastolic cavity dimension (preload) was not changed from baseline measures in either group (P < 0.05). E/A ratio was significantly lower in men and women Post [men: 1.44 (SD 1.2) vs. women: 1.32 (SD 0.6)], and this ratio was decreased to a greater degree in men (27%) relative to women (20%). The Pre-to-Post changes in E/A ratio were not significantly related to changes in heart rate (men r2 = 0.25; women r2 = 0.04). Systolic cavity dimension and heart rate were increased in men and women Post, whereas SBP was decreased in both groups (P < 0.05). Fractional area change, myocardial contractility, and wall stress were significantly lower, whereas end-systolic cavity dimension was significantly increased Post in men and women. However, men had significantly greater relative decreases compared with women for contractility (11 vs. 5%), fractional area change (6 vs. 4%), and wall stress (9 vs. 5%). These differences from preexercise values are well within changes in LV function commonly reported in the literature (33). The linear, inverse correlation between stress and fractional area change was displaced downward Post, as measured by a comparison of the y-intercepts, indicating less shortening for a given afterload in both men and women (P < 0.05; Fig. 1). The decrement in contractility Post vs. Pre was not significantly related to exercise duration in men (r2 = 0.16) or women (r2 = 0.05). All measures returned to baseline values 24 h following PSE (i.e., during Rec).


Figure 1
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  		Fig. 1. Male and female stress-shortening relationship determined by dobutamine stress echocardiography 6 days before prolonged strenuous exercise (Pre), immediately following strenuous exercise (Post), and 24 h following strenuous exercise (Rec). Calculated regression in men (A) and women (B) for end-systolic wall stress is plotted against fractional area change on prerace, postrace, and recovery recordings (before dobutamine administration). The regression line characterizing the stress-shortening relationship postrace is displaced significantly downward (y-axis intercepts are different). *P < 0.05 vs. baseline; {tau}P < 0.05 vs. women.

 
Cardiovascular responses to dobutamine.   In response to dobutamine contractility increased significantly in both groups Pre (Fig. 2). However, the increase in contractility was significantly greater in men than in women at the higher doses (P < 0.05). SBP increased significantly in response to dobutamine in both groups, but men demonstrated a greater rise in SBP (P < 0.05) than did women Pre (Fig. 2). Dobutamine induced increases in heart rate in both men and women (P < 0.05). However, men exhibited a diminished chronotropic response to dobutamine compared with women Pre (P < 0.05; Fig. 2). Consequently, women demonstrated a significantly greater chronotropic response to dobutamine, whereas men exhibited an enhanced inotropic and SBP response Pre. At race finish (Post), contractility, heart rate, and SBP increased in response to dobutamine in men and women, although the responses were significantly blunted compared with Pre (Fig. 2; P < 0.05). All measures returned to baseline values 24 h following PSE (i.e., during Rec).


Figure 2
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  		Fig. 2. Dobutamine-induced cardiovascular changes Pre and Post. Values are means ± SE. Dobutamine increased all variables in both groups; however, women showed a greater heart rate response, whereas men demonstrated a greater increase in contractility and systolic blood pressure Pre. Men demonstrated greater decreases in all variables Post. *P < 0.05 vs. baseline. {tau}P < 0.05 vs. women.

 
Chronotropic and inotropic responses to beta-adrenergic stimulation.   The chronotropic sensitivity to dobutamine, determined by the slope of the heart rate dobutamine dose-response curve, was significantly greater with a steeper slope in women than in men Pre [men: 0.93 (SD 0.99) vs. women: 1.30 (SD 1.34)]. Dobutamine doses necessary to increase heart rate were significantly increased following PSE in both men and women; however, the differences were significantly greater in men (Fig. 3; P < 0.05). Dobutamine doses necessary to increase contractility were also significantly increased in men and women postrace (Fig. 4; P < 0.05). Men required significantly more dobutamine than women to induce these changes following PSE, as evidenced by increases in x-intercepts and decreases in slopes of the dose-response relationships between heart rate, contractility, and dobutamine (Fig. 4).


Figure 3
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  		Fig. 3. Dobutamine dose necessary to increase heart rate by 25 beats/min Pre, Post, and Rec. Values are means ± SE. Dobutamine doses necessary to increase heart rate by 25 beats/min were significantly increased following PSE in both men and women; however, the differences were significantly greater in men. *P < 0.05 vs. baseline. {tau}P < 0.05 vs. women.

 

Figure 4
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  		Fig. 4. Dobutamine dose necessary to increase contractility by 10 mmHg/cm2 Pre, Post, and Rec. Values are means ± SE. Dobutamine doses necessary to increase contractility were significantly increased following prolonged strenuous exercise in both men and women; however, the differences were significantly greater in men. *P < 0.05 vs. baseline. {tau}P < 0.05 vs. women.

 
The incremental increase in dobutamine required to increase contractility by 10 mmHg/cm2 following PSE was correlated with the reduction in contractility (Fig. 5). Approximately 66% of the variance in decrements in contractility was explained by dobutamine-induced changes in heart rate (r2 = 0.66, P < 0.05). The incremental dobutamine dose was not significantly related to duration of PSE (r2 = 0.16), body size (r2 = 0.19), or LV mass normalized to lean body mass (r2 = 0.004).


Figure 5
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  		Fig. 5. Relationship between magnitude of decrease in contractility and magnitude of increase in dobutamine dosage necessary to increase contractility by 10 mmHg/cm2 in men ({circ}) and women (bullet). In general, participants requiring greater dobutamine dosages to induce a 10 mmHg/cm2 change in inotropy experienced greater decreases in contractility following prolonged strenuous exercise. All data represent changes from data obtained Pre to those obtained Post.

 
Cardiac autonomic modulation.   Parasympathetic activity was higher in women relative to men across all conditions as measured by RMSSD (P < 0.05). Mean R-R interval was significantly decreased Post compared with Pre and Rec in both men and women [men Pre: 1,099 ms (SD 183) ms vs. men Post: 820 ms (SD 216); women Pre: 1,253 ms (SD 109) vs. women Post: 893 ms (SD 260); P < 0.05]. Parasympathetic indexes (RMSSD and HF power) were reduced following PSE, although these changes were not statistically different. The sympathetic index LF power was elevated Post in men and women, although these changes did not reach statistical significance. There was also a nonsignificant increase in the ratio of LF to HF power following PSE with respect to preexercise values [men Pre: 0.70 (SD 0.21) vs. men Post 1.62 (SD 1.26); women Pre 0.48 (SD 0.22) vs. women Post 1.03 (SD 1.0)].


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 
The major novel finding of this investigation is that following an acute bout of PSE, there are significant differences in LV systolic function and beta-receptor responsiveness between male and female triathletes. Following PSE, not only does LV systolic performance decrease to a greater degree in male athletes but so too do the chronotropic and inotropic responses to beta-adrenergic stimulation. These results suggest that the decreased LV systolic performance produced by PSE may be due, in part, to greater reductions in cardiac beta-receptor responsiveness in male triathletes.

LV systolic function.   To our knowledge, this study is the first to compare LV function following PSE in both male and female athletes. Previous investigations examining this phenomenon included few female participants, or data were simply combined for both male and female participants, a process that ultimately masked the effect of PSE on LV function in women. Although one investigation reported that LV systolic function is maintained in female athletes after 2 h of PSE, no men were included for comparison (30). Furthermore, 2 h of PSE may not be sufficient to elicit significant reductions in cardiac function (31). We found that the stress-fractional area change relationship was displaced downward following PSE in both men and women; however, this decrease was significantly greater in men. Because the stress-fractional area change relationship takes into account LV loading conditions, others (15, 34, 50) have suggested that inotropic state can be inferred from this relationship. Therefore, our data not only provide evidence that decreases in LV function occur following PSE, but also demonstrate that LV systolic function is decreased to a greater extent in male athletes.

LV diastolic function.   Previously, abnormal diastolic filling has been observed during recovery from PSE (14, 15, 18, 20), potentially indicating impairment of LV relaxation and/or changes in LV compliance. E/A ratio was decreased following PSE in both men and women, and the reduction in E/A ratio was greater in men than in women. It is interesting to note that the decreases in E/A ratio following PSE were greater than the decreases in systolic function variables. Several other investigations have reported such changes in diastolic filling (15, 18, 20, 23), even without alterations in systolic function (14, 22). It is possible that alterations in diastolic function occur before decreases in systolic function, and they may even contribute to systolic dysfunction. Although heart rate and loading factors are thought to influence diastolic filling, the lack of a correlation between change in E/A ratio and change in heart rate and wall stress found in the present study, as well as others (32), suggests that PSE produces transient alterations in diastolic filling parameters that are independent of changes in loading conditions or heart rate.

beta-Receptor responsiveness.   Several mechanisms have been hypothesized to explain the observed decrease in LV function following PSE, including beta-receptor downregulation or desensitization (18, 19, 23, 51). Our finding that reduced inotropic responsiveness was correlated with the severity of LV dysfunction following PSE suggests that alterations in LV function may be partially explained by changes in cardiac beta-receptor responses. Investigators have observed previously that long-term exposure of adrenergic receptors to increased concentrations of catecholamines results in desensitization of these receptors (28). This phenomenon has clinical relevance for individuals with chronic heart failure, where elevated catecholamines and altered adrenergic responsiveness have been implicated in the pathogenesis of heart failure. Support for this theory occurring in healthy individuals was first proposed by Butler et al. (4), who suggested that altered sympathetic responses following physical training were related to decreases in beta-receptor density.

Although previous research has attempted to evaluate beta-receptor function following PSE in humans, the present investigation is the first to comprehensively assess beta-receptor responsiveness in men and women. Eysmann et al. (18) examined beta-receptor responsiveness using isoproterenol following a single bout of PSE, and they demonstrated not only that ejection fraction was reduced following prolonged exercise but also that this reduction was closely related to a decreased sensitivity to exogenous beta-receptor stimulation. However, it is important to note that the beta-agonist isoproterenol used in the investigation conducted by Eysmann and colleagues produces a logarithmic dose-response curve of changes in heart rate. This logarithmic curve potentially limits interpretation of heart rate changes, particularly if heart rate remains elevated following exercise. The beta-agonist used in our study, dobutamine, produces a linear dose-response curve. Such a curve allows us to make a valid comparison between our conditions (Pre, Post, and Rec), despite heart rate being higher following PSE. Whereas Welsh et al. (51) also used the beta-receptor agonist dobutamine, they did not calculate the slopes and intercepts of the relationship between dobutamine dose and heart rate and/or contractility. Consequently, the interpretation of beta-receptor responsiveness is somewhat limited in that investigation.

Sex differences.   Several studies have reported sex differences in cardiovascular function at rest and in commonly occurring physiological conditions such as exercise (12, 26) and orthostatic stress (11, 12). These investigations have indicated that women have a parasympathetic predominance at rest, whereas men have a dominant sympathetic regulation both at rest (9, 17, 40) and during exercise (12, 16). These increased sympathetic responses could explain the greater reductions in beta-receptor responsiveness and, consequently, the greater decreases in LV systolic function in men relative to women found in our study. Future investigations should explore the relationship between autonomic regulation and PSE in men and women in greater depth.

Although an increased sympathetic response in male athletes could be one factor contributing to larger alterations in beta-receptor responsiveness relative to women, there are several other mechanisms that could help account for the observed gender differences following PSE. The role of estrogen in cardiac physiology remains to be clarified; however, it is known that systolic and diastolic function can be altered by castration or hormone replacement (41) and that cardiac myocytes contain functional estrogen receptors (29). Although estrogen prevents, or at least slows, the development of heart failure (3), it may also play a cardioprotective role during acute bouts of exercise.

Others have proposed that alterations in cardiac metabolism due to free fatty acids, hydrogen ion content, and intracellular calcium may alter LV function (13). Chen et al. (8) demonstrated that male rats have higher sarcoplasmic reticulum calcium than female rats following isoproterenol treatment. It is possible that an increased concentration of calcium in male cardiac myocytes could interfere with cross-bridge uncoupling, thus resulting in greater diastolic dysfunction in men. Further studies are necessary to delineate these mechanistic pathways.

Cardiac autonomic modulation.   An increase in vagal tone and the resulting cardiac muscarinic receptor stimulation cause a decrease in chronotropic and inotropic activity (7). It is plausible that the mechanism underlying decreased LV function following PSE could be caused by strong vagal reactivation after exercise (27, 37). However, this rationale is refuted by several investigations. Friedman et al. (19) found that the functional desensitization following exercise was evident both with and without pretreatment with atropine, suggesting that the phenomenon was unrelated to changes in vagal tone in dogs. Hart et al. (23) also reported recently a persistent decrease in contractility following PSE, regardless of vagal inhibition. Furthermore, several other investigations have demonstrated that there is a delayed vagal reactivation following exercise in highly trained men and women (2, 36, 48). Although HRV was assessed in a subset of participants due to logistical limitations, our results also suggest there may be attenuated cardiac vagal modulation and a sympathetic predominance following PSE in both men and women. It is likely that the observed decrease in LV systolic function can be attributed to factors other than a large parasympathetic influence following PSE. Future investigations should further examine the role of the autonomic nervous system on cardiac function following PSE in men and women.

Limitations.   Several limitations should be considered when interpreting the results of the present study. First, there were significant differences in height, weight, LV mass, and VO2 max between men and women. However, these differences were removed when normalized for lean body mass. Furthermore, the decrement in inotropic responsiveness observed following PSE was not related to body mass or LV mass (r2 = 0.19 and r2 = 0.004; respectively), suggesting factors other than body size are influencing beta-receptor responsiveness and LV function. Although both groups were racing at equivalent intensities, women exercised on average 30 min longer than men. Despite this, they still maintained LV function and beta-receptor responsiveness to a greater degree than men. This supports our initial hypotheses. Second, although we were unable to assess catecholamines in the present investigation, numerous other investigations have demonstrated that in response to exercise men demonstrate a significantly greater catecholamine response than do women (12, 26, 46). Finally, this study was restricted to young, healthy participants. Previous research has demonstrated that there is an age-associated decline in inotropic and chronotropic responses to beta-adrenergic stimulation, with men exhibiting a greater decline with aging than women (49). Further studies examining beta-receptor function following an acute bout of PSE, particularly in older endurance athletes, should be carried out.

In conclusion, the present investigation demonstrated that PSE alters beta-receptor responsiveness and LV systolic function to a greater degree in men relative to women. Further investigation into the delineation of the mechanisms of such altered responsiveness and additional exploration of the physiological relevance for cardiovascular performance during exercise in healthy adults is warranted.


   GRANTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
ACKNOWLEDGMENTS
 REFERENCES
 
This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research (CIHR), the Canada Foundation for Innovation, the British Columbia Knowledge Development Fund, and the Michael Smith Foundation for Health Research (MSFHR). M. J. Haykowsky and D. E. R. Warburton are CIHR New Investigators. D. E. R. Warburton is also a MSFHR Scholar.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
REFERENCES
 
The authors thank the subjects for enthusiastic participation. We gratefully acknowledge Lan Hu and Ala Kudukhova for technical assistance.


   FOOTNOTES
 

Address for reprint requests and other correspondence: D. E. R. Warburton, 6108 Thunderbird Blvd., Univ. of British Columbia, Vancouver, BC, Canada V6T 1Z3 (e-mail: darren.warburton{at}ubc.ca)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 GRANTS
 ACKNOWLEDGMENTS
 REFERENCES
 

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