Effect of Daily Exercise on Cardiac Autonomic Regulation

Summary

Principal Investigator: GEORGE BILLMAN
Abstract: Epidemiological data demonstrate that aerobic exercise training can dramatically reduce cardiac mortality even in patients with pre-existing cardiac disease. The mechanisms responsible for this cardio protection remain largely to be determined. It is probable that exercise-induced changes in cardiac autonomic regulation play a major role in the improved cardiac mortality. Cardiac autonomic balance is altered by cardiac disease and the patients with the greatest changes (i.e., decreased parasympathetic and/or increased sympathetic activity) are also at the greatest risk for sudden death presumably due to ventricular fibrillation (VF). Exercise training can increase parasympathetic and decrease sympathetic activity and could thereby reduce mortality. Therefore, the proposed studies will test the central hypothesis that exercise training augments parasympathetic and/or reduces cardiac sympathetic activity and thereby protects against VF. Specific Aim #1 will test the hypothesis that exercise training alters cardiac autonomic balance in animals susceptible and resistant to VF. Specifically, cardiac autonomic balance will be evaluated in animals either resistant or susceptible to VF before, during and after the completion of an exercise conditioning program (8-10 weeks of daily treadmill running). The autonomic response to two different physiological stressors, submaximal exercise and acute myocardial ischemia, will be evaluated. Cardiac autonomic balance will be evaluated by pharmacological tests (agonist dose response, effects of selective antagonists), baroreflex sensitivity, and time series analysis of R-R interval variability. Specific Aim #2 will test the hypothesis that the cardiac autonomic changes induced by exercise training are responsible for the protection noted for this intervention. The effects of parasympathetic activity will be evaluated with a cholinergic antagonist. Thus, if parasympathetic enhancement is responsible for the protection, then atropine should reinstate VF in the susceptible animals. Specific Aim #3 will test the hypothesis that exercise training can reverse the increased Beta-adrenoceptor responsiveness that we have shown to occur in dogs that become susceptible to VF following myocardial infarction. Ventricular contractile responses to Beta1- and Beta2-adrenoceptor stimulation will be examined in vivo by echocardiography and in vitro by single cell fluorescence microscopy/video edge detection.
Funding Period: 2002-07-01 - 2007-06-30
more information: NIH RePORT

Top Publications

  1. pmc Shortened Ca2+ signaling refractoriness underlies cellular arrhythmogenesis in a postinfarction model of sudden cardiac death
    Andriy E Belevych
    Davis Heart and Lung Research Institute, The Ohio State University Medical Center, 473 W 12th Ave, Columbus, OH 43210, USA
    Circ Res 110:569-77. 2012
  2. pmc Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death
    Andriy E Belevych
    Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, College of Medicine, Columbus, OH 43210, USA
    Cardiovasc Res 84:387-95. 2009
  3. pmc Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death
    Arun Sridhar
    Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio 43210, USA
    Am J Physiol Regul Integr Comp Physiol 295:R1463-72. 2008
  4. ncbi Electrotonic remodeling following myocardial infarction in dogs susceptible and resistant to sudden cardiac death
    Carlos L del Rio
    Dept of Physiology and Cell Biology, The Ohio State Univ, 1645 Neil Ave, 305 Hamilton Hall, Columbus, OH 43210, USA
    J Appl Physiol (1985) 104:386-93. 2008
  5. ncbi Exercise training normalizes beta-adrenoceptor expression in dogs susceptible to ventricular fibrillation
    Bethany J Holycross
    Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 293:H2702-9. 2007
  6. pmc n-3 (omega-3) polyunsaturated fatty acids prevent acute atrial electrophysiological remodeling
    D N Q da Cunha
    Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
    Br J Pharmacol 150:281-5. 2007
  7. ncbi Effect of endurance exercise training on heart rate onset and heart rate recovery responses to submaximal exercise in animals susceptible to ventricular fibrillation
    George E Billman
    Department of Physiology and Cell Biology, The Ohio State University, 304 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210 1218, USA
    J Appl Physiol (1985) 102:231-40. 2007
  8. ncbi Heart rate response to onset of exercise: evidence for enhanced cardiac sympathetic activity in animals susceptible to ventricular fibrillation
    George E Billman
    Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 291:H429-35. 2006
  9. ncbi A comprehensive review and analysis of 25 years of data from an in vivo canine model of sudden cardiac death: implications for future anti-arrhythmic drug development
    George E Billman
    Department of Physiology and Cell Biology, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 1218, United States
    Pharmacol Ther 111:808-35. 2006
  10. ncbi Endurance exercise training attenuates cardiac beta2-adrenoceptor responsiveness and prevents ventricular fibrillation in animals susceptible to sudden death
    George E Billman
    Department of Physiology and Cell Biology, The Ohio State University, 1645 Neil Avenue, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 290:H2590-9. 2006

Scientific Experts

  • GEORGE BILLMAN
  • Monica Kukielka
  • Andriy E Belevych
  • Cynthia A Carnes
  • Radmila Terentyeva
  • Sandor Gyorke
  • Dmitry Terentyev
  • Arun Sridhar
  • Yoshinori Nishijima
  • Ingrid M Bonilla
  • Carlos L del Rio
  • Bethany J Holycross
  • D N Q da Cunha
  • Lauren L Smith
  • Hyosook Hwang
  • Inna Gyorke
  • Hsiang Ting Ho
  • Lance D Wilson
  • Serge Viatchenko-Karpinski
  • Kenneth R Laurita
  • Arturo J Cardounel
  • Rebecca Uelmen
  • Bradley D Clymer
  • Patrick I McConnell
  • Roger Dzwonczyk
  • Gail A Robertson
  • Michael B Howie
  • Ruth A Altschuld
  • C A Carnes
  • R L Hamlin
  • Douglas R Seals
  • Peter J Reiser

Detail Information

Publications14

  1. pmc Shortened Ca2+ signaling refractoriness underlies cellular arrhythmogenesis in a postinfarction model of sudden cardiac death
    Andriy E Belevych
    Davis Heart and Lung Research Institute, The Ohio State University Medical Center, 473 W 12th Ave, Columbus, OH 43210, USA
    Circ Res 110:569-77. 2012
    ....
  2. pmc Redox modification of ryanodine receptors underlies calcium alternans in a canine model of sudden cardiac death
    Andriy E Belevych
    Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, The Ohio State University, College of Medicine, Columbus, OH 43210, USA
    Cardiovasc Res 84:387-95. 2009
    ....
  3. pmc Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death
    Arun Sridhar
    Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio 43210, USA
    Am J Physiol Regul Integr Comp Physiol 295:R1463-72. 2008
    ..These abnormalities may provide a substrate for initiation of postmyocardial infarction ventricular tachyarrhythmias...
  4. ncbi Electrotonic remodeling following myocardial infarction in dogs susceptible and resistant to sudden cardiac death
    Carlos L del Rio
    Dept of Physiology and Cell Biology, The Ohio State Univ, 1645 Neil Ave, 305 Hamilton Hall, Columbus, OH 43210, USA
    J Appl Physiol (1985) 104:386-93. 2008
    ..In addition, passive-electrical changes could be a mechanism driving active-electrical remodeling post-MI, thereby facilitating the induction of arrhythmias...
  5. ncbi Exercise training normalizes beta-adrenoceptor expression in dogs susceptible to ventricular fibrillation
    Bethany J Holycross
    Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 293:H2702-9. 2007
    ..These data suggest that beta(1)-AR gene expression was decreased in susceptible dogs compared with resistant dogs and, further, that exercise training improves beta(1)-AR gene expression, thereby restoring a more normal beta-AR balance...
  6. pmc n-3 (omega-3) polyunsaturated fatty acids prevent acute atrial electrophysiological remodeling
    D N Q da Cunha
    Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
    Br J Pharmacol 150:281-5. 2007
    ..We hypothesized that n-3 PUFAs would attenuate early atrial electrophysiolgical remodeling in a canine model of acute atrial tachypacing...
  7. ncbi Effect of endurance exercise training on heart rate onset and heart rate recovery responses to submaximal exercise in animals susceptible to ventricular fibrillation
    George E Billman
    Department of Physiology and Cell Biology, The Ohio State University, 304 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210 1218, USA
    J Appl Physiol (1985) 102:231-40. 2007
    ..8 vs. posttraining 159.4 +/- 7.7 beats/min; HRV pretraining 2.4 +/- 0.3 vs. posttraining 4.0 +/- 0.6 ln ms(2)). Thus endurance exercise training restored a more normal HR regulation in dogs susceptible to VF...
  8. ncbi Heart rate response to onset of exercise: evidence for enhanced cardiac sympathetic activity in animals susceptible to ventricular fibrillation
    George E Billman
    Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 291:H429-35. 2006
    ....
  9. ncbi A comprehensive review and analysis of 25 years of data from an in vivo canine model of sudden cardiac death: implications for future anti-arrhythmic drug development
    George E Billman
    Department of Physiology and Cell Biology, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 1218, United States
    Pharmacol Ther 111:808-35. 2006
    ....
  10. ncbi Endurance exercise training attenuates cardiac beta2-adrenoceptor responsiveness and prevents ventricular fibrillation in animals susceptible to sudden death
    George E Billman
    Department of Physiology and Cell Biology, The Ohio State University, 1645 Neil Avenue, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 290:H2590-9. 2006
    ..Thus exercise training can restore cardiac beta-AR balance (by reducing beta(2)-AR responsiveness) and could, thereby, prevent VF...
  11. ncbi Cardiac vagal modulation of heart rate during prolonged submaximal exercise in animals with healed myocardial infarctions: effects of training
    Monica Kukielka
    Dept of Physiology, The Ohio State University, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 290:H1680-5. 2006
    ..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...
  12. ncbi Effects of endurance exercise training on heart rate variability and susceptibility to sudden cardiac death: protection is not due to enhanced cardiac vagal regulation
    George E Billman
    Dept of Physiology and Cell Biology, The Ohio State Univ, 304 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210 1218, USA
    J Appl Physiol (1985) 100:896-906. 2006
    ..Atropine decreased HRV but only induced VF in one of eight trained susceptible dogs. Thus exercise training increased cardiac vagal activity, which was not solely responsible for the training-induced VF protection...
  13. ncbi Effects of exercise training on contractile function in myocardial trabeculae after ischemia-reperfusion
    Hyosook Hwang
    Section of Sport and Exercise Sciences, School of Physical Activity and Educational Services, The Ohio State Univ, Columbus, OH, USA
    J Appl Physiol 99:230-6. 2005
    ..Nevertheless, the trained myocardium appears to have a greater maximum force-generating ability that may, at least partially, compensate for reduced contractile function induced by a brief period of ischemia...
  14. ncbi Heart rate recovery after exercise: a predictor of ventricular fibrillation susceptibility after myocardial infarction
    Lauren L Smith
    Dept of Physiology and Cell Biology, The Ohio State University, 304 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 1218, USA
    Am J Physiol Heart Circ Physiol 288:H1763-9. 2005
    ..As such, postexercise heart rate recovery may help identify patients with a high risk for VF following myocardial infarction...