Cardiac vagal modulation of heart rate during prolonged submaximal exercise in animals with healed myocardial infarctions: effects of training.
ABSTRACT The present study investigated the effects of long-duration exercise on heart rate variability [as a marker of cardiac vagal tone (VT)]. Heart rate variability (time series analysis) was measured in mongrel dogs (n = 24) with healed myocardial infarctions during 1 h of submaximal exercise (treadmill running at 6.4 km/h at 10% grade). Long-duration exercise provoked a significant (ANOVA, all P < 0.01, means +/- SD) increase in heart rate (1st min, 165.3 +/- 15.6 vs. last min, 197.5 +/- 21.5 beats/min) and significant reductions in high frequency (0.24 to 1.04 Hz) power (VT: 1st min, 3.7 +/- 1.5 vs. last min, 1.0 +/- 0.9 ln ms(2)), R-R interval range (1st min, 107.9 +/- 38.3 vs. last min, 28.8 +/- 13.2 ms), and R-R interval SD (1st min, 24.3 +/- 7.7 vs. last min 6.3 +/- 1.7 ms). Because endurance exercise training can increase cardiac vagal regulation, the studies were repeated after either a 10-wk exercise training (n = 9) or a 10-wk sedentary period (n = 7). After training was completed, long-duration exercise elicited smaller increases in heart rate (pretraining: 1st min, 156.0 +/- 13.8 vs. last min, 189.6 +/- 21.9 beats/min; and posttraining: 1st min, 149.8 +/- 14.6 vs. last min, 172.7 +/- 8.8 beats/min) and smaller reductions in heart rate variability (e.g., VT, pretraining: 1st min, 4.2 +/- 1.7 vs. last min, 0.9 +/- 1.1 ln ms(2); and posttraining: 1st min, 4.8 +/- 1.1 vs. last min, 2.0 +/- 0.6 ln ms(2)). The response to long-duration exercise did not change in the sedentary animals. Thus the heart rate increase that accompanies long-duration exercise results, at least in part, from reductions in cardiac vagal regulation. Furthermore, exercise training attenuated these exercise-induced reductions in heart rate variability, suggesting maintenance of a higher cardiac vagal activity during exercise in the trained state.
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ABSTRACT: Fluctuations in heart rate above 0.03 Hz reflect autonomic modulation of sinoatrial node activity. To assess the dynamics of autonomic nervous activity during and immediately after exercise, we determined the power spectrum of heart rate and respiratory fluctuations in 43 normal subjects without known cardiac disease, 8 patients with severe congestive heart failure, and 6 patients status-post cardiac transplantation before, during, and after graded-work load exercise on a cycle ergometer. Before exercise, heart rate fluctuations (spectral power) at both high (0.15-0.80 Hz) and low (0.03-0.15 Hz) frequencies were significantly higher in normal subjects than in either heart failure or transplant patients but were not different between the two groups with heart disease. During exercise, heart rate power at all frequencies rapidly and progressively decreased in normal subjects, until at peak exercise it was not different from the other two groups. During recovery, heart rate power increased in normal subjects but remained significantly below base line. The findings demonstrate a marked reduction of autonomic modulation of heart rate in patients with heart failure and after cardiac transplant and support a progressive withdrawal of vagal activity during exercise with a gradual increase during recovery in normal subjects.The American journal of physiology 02/1989; 256(1 Pt 2):H132-41. · 3.28 Impact Factor
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ABSTRACT: □ ZielDie Arbeit untersucht den Einfluß regelmäßiger körperlicher Aktivität und akuter körperlicher Belastungssituationen auf die Inzidenz des plötzlichen Herztodes in der Bevölkerung von zwei Berliner Stadtteilen mit 219 251 Einwohnern in der untersuchten Altersgruppe. □ Patienten und MethodeAlle plötzlichen Herztodesfälle außerhalb eines Krankenhauses mit dokumentiertem Kammerflimmern in der untersuchten Bevölkerung wurden über 18 Monate erfaßt und für jeden Betroffenen die regelmäßig absolvierte körperliche Aktivität und die Belastung bei Eintritt des plötzlichen Herztodes ermittelt. Mit den Daten über das Aktivitätsmuster der untersuchten Bevölkerung wurde die Inzidenz des plötzlichen Herztodes in Gruppen mit unterschiedlicher regelmäßiger körperlicher Belastung und das relative Risiko für den plötzlichen Herztod bei einer aktuellen körperlichen Belastungssituation im Vergleich zur Ruhe berechnet. Der Einfluß von Vorerkrankungen wurde ermittelt. □ Ergebnisse77 Patienten mit plötzlichem Herztod durch Kammerflimmern wurden eingeschlossen. In der Gruppe, die sich nie regelmäßig körperlich belastet, fand sich eine Inzidenz von 4,69 plötzlichen Herztoden/105 Personen-jahren, in der Gruppe mit niedriger regelmäßiger körperlicher Aktivität eine Inzidenz von 4,25, in der Gruppe mit mittlerer regelmäßiger körperlicher Aktivität eine Inzidenz von 2,63 und in der aktivsten Gruppe eine von 0,92 plötzlichen Herztoden/105 Personenjahren. Das relative Risiko für den plötzlichen Herztod bei Belastung im Vergleich zur Ruhe war in der Gruppe mit niedriger regelmäßiger körperlicher Aktivität 150 und in der aktivsten Gruppe 4. Die Vorerkrankungen der Fallgruppe hatten keinen Einfluß auf das Ergebnis. □ SchlußfolgerungDie Ergebnisse zeigen, daß für alle Menschen unabhängig von der gewohnten körperlichen Aktivität und den Vorerkrankungen anstrengende körperliche Belastung mit einem gegenüber der Ruhe deutlich erhöhten Risiko für den plötzlicher Herztod verbunden ist. Die Risikozunahme für den plötzlichen Herztod bei körperlicher Aktivität ist für Menschen mit einem passiven Lebensstil am stärksten, für Menschen mit einem aktiven Lebensstil am wenigsten ausgeprägt. Der protektive Effekt regelmäßiger körperlicher Aktivität für den plötzlichen Herztod übertrifft aber die Risikozunahme durch die aktuelle Belastungssituation. □ AimOur investigation examined the influence of regular physical activity and sudden extrenious situations on the incidence of sudden cardiac death (scd) in two different Berlin districts with a total population of 219,251 in the examined agegroups. □ Patients and MethodAll cases of scd which occured outside of the hospital and were documented as been induced from ventricular fibrillation were examined over a time period of 18 months. For each case the amount of and the intensity of their regular physical activity was determined. In addition the stress of the sudden extrenious situations was survied. The study population was divided into various groups depending upon their level of regular physical activity. For each group the incidence of sudden cardiac death was determined. The the relative risk for scd during strenuous activity compared to inactivity was determined for each group. The influence of preexisting disease was calculated. □ Results77 patients with scd induced from ventricular fibrillation were included in our study. In the sedentary group we found an incidence of 4.69 scd per 105 personyears, in the group with a low level of regular physical activity we found an incidence of 4.25, in the group with a middle level of regular physical activity an incidence of 2.63 and in the most active group 0.92 scd per 105 personyears. We found the relative risk for scd during highly strenuous activity compared with inactivity to be 150 in the sedentary group as opposed to 4.0 in the most active group. The preexisting illness status of the case groups had no influence on the outcome. □ ConclusionsThe results show that the risk of scd for all persons regardless of their levels of regular physical activity and their preillness status is higher during strenuous activity than during inactivity. The increase of the risk for scd during activity is the highest for persons with sedentary lifestyles, whereas the risk increase for persons with active lifestyles is minimal. The protective effect of regular physical activity for scd by far exceeds the risk increase of the actual strenuous situation.92(6):319-325.
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ABSTRACT: Sudden, unexpected cardiac death due to ventricular fibrillation is the leading cause of death in most industrially developed countries. Yet, despite the enormity of this problem, the development of safe and effective antiarrhythmic therapies has proven to be an elusive goal. In fact, many initially promising antiarrhythmic medications were subsequently found to increase rather than to decrease cardiac mortality. It is now known that cardiac disease alters cardiac autonomic balance and that the patients with the greatest changes in this cardiac neural regulation (i.e., decreased parasympathetic coupled with increased sympathetic activity) are also the patients at the greatest risk for sudden death. A growing body of experimental and epidemiological data demonstrates that aerobic exercise conditioning can dramatically reduce cardiac mortality, even in patients with preexisting cardiac disease. Conversely, the lack of exercise is strongly associated with an increased incidence of many chronic debilitating diseases, including coronary heart disease. Because it is well established that aerobic exercise conditioning can alter autonomic balance (increasing parasympathetic tone and decreasing sympathetic activity), a prudently designed exercise program could prove to be an effective and nonpharmacological way to enhance cardiac electrical stability, thereby protecting against sudden cardiac death.Journal of Applied Physiology 03/2002; 92(2):446-54. · 3.48 Impact Factor
“FINAL ACCEPTED VERSION”
Title: Cardiac Vagal Modulation of Heart Rate During Prolonged Submaximal Exercise in
Animals with Healed Myocardial Infarctions: Effects of Training
Authors: Monica Kukielka1, Douglas R. Seals2, and George E. Billman1
1Department of Physiology and Cell Biology, The Ohio State University,
Columbus, OH and 2Department of Integrative Physiology, University of Colorado at Boulder,
Address for Correspondence: George E. Billman, Ph.D., F.A.H.A.
Department of Physiology and Cell Biology
The Ohio State University
304 Hamilton Hall
1645 Neil Ave.
Columbus OH 43210-1218
Telephone: (614) 292-5189
Fax: (614) 292-4888
Running title: Heart rate variability is reduced during exercise
Articles in PresS. Am J Physiol Heart Circ Physiol (December 9, 2005). doi:10.1152/ajpheart.01034.2005
Copyright © 2005 by the American Physiological Society.
The present study investigated the effects of long-duration exercise on heart rate variability (as a
marker of cardiac vagal activity, VT). Heart rate variability (time series analysis) was measured
in mongrel dogs (n=24) with healed myocardial infarctions during 1 hour of submaximal
exercise (treadmill running at 6.4 kph/10% grade). Long-duration exercise provoked a
significant (ANOVA, all P<0.01, mean±SD) increase in heart rate (1st min 165.3±15.6 vs. last
min 197.5±21.5 beats/min) and significant reductions in high frequency (0.24 to 1.04 Hz) power
(VT, 1st min 3.7±1.5 vs. last min, 1.0±0.9 ln ms2), R-R interval range (1st min 107.9±38.3 vs. last
min, 28.8±13.2 ms), and R-R interval SD (1st min 24.3±7.7 vs. last min 6.3±1.7 ms). As
endurance exercise training can increase cardiac vagal regulation, the studies were repeated after
either a 10-week exercise training (n=9) or a 10-week sedentary period (n=7). After training,
long-duration exercise elicited smaller increases in heart rate (pre-training, 1st min 156.0±13.8
vs. last min 189.6±21.9; post-training, 1st min 149.8±14.6 vs. last min 172.7±8.8 beats/min) and
smaller reductions in heart rate variability (e.g., VT, pre-training, 1st min 4.2±1.7 vs. last min
0.9±1.1; post-training, 1st min 4.8±1.1 vs. last min 2.0±0.6 ln ms2). The response to long-
duration exercise did not change in the sedentary animals. Thus, the heart rate increase that
accompanies long-duration exercise results, at least in part, from reductions in cardiac vagal
regulation. Furthermore, exercise training attenuated these exercise-induced reductions in heart
rate variability, suggesting maintenance of a higher cardiac vagal activity during exercise in the
Key Words: parasympathetic nervous system, exercise training, autonomic nervous system
Myocardial infarction elicits profound alterations in cardiac autonomic regulation (10).
In particular, cardiac vagal regulation is depressed in both animals and patients following
myocardial infarction (3, 7, 20, 39). In fact, animals or patients with the greatest reductions in
heart rate variability, an accepted non-invasive marker of cardiac vagal regulation (13, 40),
exhibit the greatest risk for sudden death due to malignant changes in cardiac rhythm (i.e.,
ventricular fibrillation) (7, 17, 22, 24, 36). It is therefore likely that interventions that enhance
cardiac vagal function could also reduce mortality in these high-risk patients.
It is well established that regular exercise can improve cardiac autonomic balance
(increasing parasympathetic while decreasing sympathetic regulation of the heart) (35, 41). In
both man and animals, heart rate at submaximal-workloads is reduced in trained individuals
compared to sedentary controls (35, 41), while the presence of a resting bradycardia is frequently
used to confirm that training has been effective (9, 16, 27, 37, 44). Exercise training programs
have also been reported to increase heart rate variability in patients recovering from myocardial
infarction (25, 28, 31) and may reduce the incidence of sudden death and arrhythmias in both
man and animal models (5, 8, 29, 33). As such, aerobic exercise conditioning has become an
essential component of most cardiac rehabilitation programs (14, 26). In order to achieve the
maximum benefit (i.e., reductions in secondary cardiovascular events), an individual should
exercise continuously for at least 20-60 minutes several days a week (14, 26).
Acute exercise, however, could pose a risk in some patients (1). Exercise provokes
increases in heart rate by both increasing cardiac sympathetic and reducing cardiac
parasympathetic activity. These autonomic changes have been linked to an enhanced risk for
sudden death in post-myocardial infarction patients (10). Furthermore, during long-duration
exercise, heart rate continues to rise throughout the exercise period, a phenomenon known as
cardiovascular (or heart rate) drift (11). The mechanisms responsible for this heart rate increase
are presently unknown. A gradual withdrawal or inhibition of cardiac parasympathetic activity
could contribute to this heart rate increase, which potentially could increase the risk for adverse
events in the patients with cardiovascular disease.
It was therefore the purpose of this study to investigate the effects of long-duration
exercise on heart rate variability in mongrel dogs with healed myocardial infractions. In
particular, the hypothesis that exercise-induced increases in heart rate were accompanied by
progressively increasing reductions in heart rate variability was tested. The effects of exercise
training on the heart rate and heart rate variability response to long-duration exercise were also
examined. As such, the hypothesis that exercise training would attenuate the progressive
reductions in heart rate variability induced by long-duration exercise was also tested.
The principles governing the care and use of animals as expressed by the Declaration of
Helsinki, and as adopted by the American Physiological Society, were followed at all times
during this study. In addition, the Ohio State University Institutional Animal Care and Use
Committee approved all the procedures used in this study.
Thirty-six heartworm free mongrel dogs (age 1-3 years) weighing 16.4 – 24.5 kg (19.2 ±
1.8 kg) were used in this study. The animals were anesthetized and instrumented as previously
described (7, 8, 17, 36). Briefly, using strict aseptic procedures, a left thoracotomy was made in
the fourth intercostal space. The heart was exposed and supported by a pericardial cradle. The
left circumflex coronary artery was dissected free of the surrounding tissue. Both a 20 MHz
pulsed Doppler flow transducer and a hydraulic occluder were then placed around this vessel.
Two pairs of silver coated copper wires were also sutured on the epicardial surface of the left and
right ventricles and were used to obtain a ventricular electrogram. A two-stage occlusion of the
left anterior descending artery was then performed approximately one-third the distance from its
origin in order to produce an anterior wall myocardial infarction. This vessel was partially
occluded for 20 minutes and then tied off. Twelve dogs died within the first 72-hrs of the
myocardial infarction. Thus, studies were completed on 24 dogs.
Long-duration Exercise Protocol
The studies began 3-4 weeks after the production of the myocardial infarction. During
this recovery period, the dogs were trained to run on a motor driven treadmill. The cardiac
response to long-duration exercise was then determined. Pre-exercise values for heart rate and