Viewpoint: is the resting bradycardia in athletes the result of remodeling of the sinoatrial node rather than high vagal tone?

IT IS WELL KNOWN THAT ATHLETES have a low resting heart rate, i.e., a resting bradycardia and heart rates below 30 beats/min have been reported (7). For example, Wikipedia states that the Tour de France cyclist, Miguel Indurain, had a resting heart rate of 28 beats/min when race fit. The resting bradycardia in athletes is most often attributed to high vagal tone, i.e., high parasympathetic nerve activity (e.g., Ref. 1). However, over the years doubt about this explanation has been expressed (e.g., Ref. 26). Here we take a critical look at the two lines of evidence said to favor the high vagal tone hypothesis: 1) little or no change in the intrinsic heart rate in athletes and 2) an increase in heart rate variability in athletes. Effect of training on intrinsic heart rate in humans. Jose and Taylor (9) investigated the effect of autonomic blockade in conscious human subjects and concluded that injection of 0.2 mg/kg propranolol ( -adrenergic receptor blocker) and 0.04 mg/kg atropine (M2 muscarinic receptor blocker) effectively blocks autonomic influence on the resting heart rate in the human. They obtained dose-response curves for both drugs to ensure that there was complete blockade (9). This pioneering study established a technique that can be used to study the nature of the resting bradycardia in athletes. Since the effect of athletic training on the resting heart rate before and after autonomic blockade has been extensively investigated in the human and these studies are summarized in Table 1. In three studies (1–3 in Table 1), only the parasympathetic activity to the heart was blocked. In all three studies, there was a significant resting bradycardia as expected in the athletes [see heart rate (HR) data for studies 1–3 in Table 1]. The resting heart rate after parasympathetic blockade was also lower in the athletes (see HR data for studies 1–3 in Table 1), and in all studies the difference in the heart rate after parasympathetic blockade was greater than the difference in the normal heart rate (compare HR and HR data for studies 1–3 in Table 1). This suggests that high vagal tone is not the cause of the resting bradycardia in the athletes in these three studies at least. Instead it could be the result of either a decrease in sympathetic tone or a decrease in the intrinsic heart rate in the athletes. In eight studies (4–11 in Table 1), the effect of complete autonomic blockade was studied. The heart rate after complete autonomic blockade is a measure of the intrinsic heart rate. In all eight studies, there was a significant decrease in the normal heart rate with training (see HR data for studies 4–11 in Table 1), and, in all but one study, the significant decrease in heart rate persisted after complete autonomic blockade (see HR data for studies 4–11 in Table 1). The final column in Table 1 shows the decrease in the heart rate after complete autonomic blockade ( HR) as a percentage of the decrease in the normal heart rate ( HR). In four out of the eight studies (4–6 and 11 in Table 1), the decrease in the heart rate after complete autonomic blockade was greater than the decrease in the normal heart rate ( HR/ HR 100%; bold in Table 1). This suggests that neither high vagal tone nor reduced sympathetic tone is the cause of the resting bradycardia in the athletes in these four studies at least and instead it is the result of a decrease in the intrinsic heart rate—in fact these data suggest that there may be a decrease in vagal tone (or an increase in sympathetic tone). However, in one of the studies (7 in Table 1) there was no significant decrease in the heart rate after complete autonomic blockade and, in three other studies (8–10 in Table 1), the decrease in the heart rate after complete autonomic blockade was less than the decrease in the normal heart rate ( HR/ HR 100%). In these studies (7–10 in Table 1), the decrease in the intrinsic heart rate accounts for between 11 and 60% of the decrease in the normal heart rate; it is possible, theoretically at least, that high vagal tone accounts for the remainder. However, there is a surprising variation in the intrinsic heart rate, i.e., the heart rate after complete autonomic blockade, in untrained individuals from 83 to 108 beats/min in studies 4–11 in Table 1. The largest study of the intrinsic heart rate in humans was performed by Jose and Collison (8), who measured the intrinsic heart rate (after complete autonomic blockade) in 432 healthy adult human subjects. It was age dependent and for the 152 subjects 20–30 years of age in their study it was 105.5 0.7 (mean standard error of the mean) beats/ min (8). Studies 4–11 in Table 1 are ranked according to the reported heart rate after complete autonomic blockade in untrained individuals. In studies 4–7 in Table 1, the heart rate after complete autonomic blockade is within the mean 2 SD, a range that will encompass 95.4% of the data, from Jose and Collison (8), i.e., from 89.4 to 121.6 beats/min. However, in studies 8–11 in Table 1, the heart rate after complete autonomic blockade is below this range. The reason for this is unclear, but it is a cause for concern. If only studies 4–7 in Table 1 are considered [in which the reported heart rate after complete autonomic blockade in young untrained individuals is within the range of the mean 2 SD from Jose and Collison (8)], the decrease in the heart rate after complete autonomic blockade was greater than the decrease in the normal heart rate ( HR/ HR 100%) in three of the four studies (4–6 in Table 1). In summary, analysis of the heart rate in athletes after autonomic blockade shows that the resting bradycardia in athletes is in part at least and perhaps even completely the result of a decrease in the intrinsic heart rate. M. R. Boyett and A. D’Souza contributed equally to this work. Address for reprint requests and other correspondence: M. R. Boyett, Institute of Cardiovascular Sciences, Univ. of Manchester, Core Technology Facility, 46 Grafton St., Manchester, M13 9NT (e-mail: [email protected]). J Appl Physiol 114: 1351–1355, 2013; doi:10.1152/japplphysiol.01126.2012. Perspectives