Changes in sinus node function in a rabbit model of heart failure with ventricular arrhythmias and sudden death.

BACKGROUND Heart failure is associated with profound changes in the balance of the autonomic nervous system, such as vagal withdrawal and increased catecholamine levels. It is not known whether the intrinsic sinus node function changes during the progression of heart failure. METHODS AND RESULTS We implanted transmitters for Holter recording in an established rabbit model of heart failure (n=9) and observed changes in sinus cycle length and the occurrence of arrhythmias during the progression of heart failure. The in vitro sinus cycle length and the responses to acetylcholine and norepinephrine in the isolated right atria were analyzed in 12 rabbits with heart failure and in 6 control rabbits. In vivo cycle length increased in some animals and decreased in others. Sudden death occurred in 3 of 9 rabbits. These rabbits had developed a shorter cycle length than the surviving rabbits. Ventricular tachycardias developed in all but 1 rabbit. The in vitro sinus cycle length increased in heart failure. The response to acetylcholine also increased in heart failure, whereas the response to norepinephrine was unchanged. CONCLUSIONS Changes in intrinsic sinus node function during the progression of heart failure cannot explain the observed decreases in heart rate variability and/or baroreflex sensitivity in this disease, because increased responsiveness to acetylcholine would be expected to cause the opposite.

[1]  J M de Bakker,et al.  Triggered activity and automaticity in ventricular trabeculae of failing human and rabbit hearts. , 1994, Cardiovascular research.

[2]  W. Stevenson,et al.  Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. , 1989, Circulation.

[3]  F. Khaja,et al.  Efficacy of propranolol therapy after acute myocardial infarction related to coronary arterial anatomy and left ventricular function. , 1987, The American journal of cardiology.

[4]  A. D. Jose,et al.  Autonomic blockade by propranolol and atropine to study intrinsic myocardial function in man. , 1969, The Journal of clinical investigation.

[5]  W. Kannel,et al.  Changing epidemiological features of cardiac failure. , 1994, British heart journal.

[6]  H. Jongsma,et al.  Functional and morphological organization of the guinea-pig sinoatrial node compared with the rabbit sinoatrial node. , 1985, Journal of molecular and cellular cardiology.

[7]  M. Allessie,et al.  Atrial and ventricular fibrillation : mechanisms and device therapy , 1997 .

[8]  F. Müller,et al.  Adrenergic and muscarinic receptor regulation and therapeutic implications in heart failure , 2004, Molecular and Cellular Biochemistry.

[9]  T. Opthof,et al.  The normal range and determinants of the intrinsic heart rate in man. , 2000, Cardiovascular research.

[10]  C. White Abnormalities in baroreflex control of heart rate in canine heart failure. , 1981, The American journal of physiology.

[11]  Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction. Results of a two-year follow-up study. , 1996, Journal of the American College of Cardiology.

[12]  F. Tristani,et al.  A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. , 1991, The New England journal of medicine.

[13]  J. Boineau,et al.  Relative densities of muscarinic cholinergic and beta-adrenergic receptors in the canine sinoatrial node and their relation to sites of pacemaker activity. , 1995, Circulation research.

[14]  D L Eckberg,et al.  Defective cardiac parasympathetic control in patients with heart disease. , 1971, The New England journal of medicine.

[15]  A. D. Jose,et al.  The normal range and determinants of the intrinsic heart rate in man. , 1970, Cardiovascular research.

[16]  P. Schwartz,et al.  Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. , 1992, Circulation.

[17]  J F Leclercq,et al.  Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. , 1989, American heart journal.

[18]  J. Floras Clinical aspects of sympathetic activation and parasympathetic withdrawal in heart failure. , 1993, Journal of the American College of Cardiology.

[19]  E. Braunwald,et al.  Sympathetic and parasympathetic components of reflex tachycardia induced by hypotension in conscious dogs with and without heart failure. , 1974, Cardiovascular research.

[20]  H. Jongsma,et al.  Cycle length dependence of the chronotropic effects of adrenaline and acetylcholine in the rabbit sinoatrial node. , 1983, Journal of the autonomic nervous system.