This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Adamson, P. B. Articles by Vanoli, E. Search for Related Content PubMed PubMed Citation Articles by Adamson, P. B. Articles by Vanoli, E.

EXPERIMENTAL STUDY

Early autonomic and repolarization abnormalities contribute to lethal arrhythmias in chronic ischemic heart failure

Characteristics of a novel heart failure model in dogs with postmyocardial infarction left ventricular dysfunction

Philip B. Adamson, MD, FACC^a and Emilio Vanoli, MD^a

^a W.K. Warren Medical Research Institute, Departments of Physiology and Medicine/Cardiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Dipartimento di Cardiologia, Universita’ di Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy

Manuscript received June 1, 2000; revised manuscript received December 21, 2000, accepted January 17, 2001.

Reprint requests and correspondence: Dr. Philip B. Adamson, Department of Internal Medicine, Cardiology, P.O. Box 26901, WP3120, Oklahoma City, Oklahoma 73190
Philip-adamson{at}ouhsc.edu

OBJECTIVES

Using a model of arrhythmias associated with ischemic left ventricular (LV) dysfunction, this study investigated autonomic and electrophysiologic mechanisms associated with sudden cardiac death (SCD) in chronic heart failure (HF).

BACKGROUND

Left ventricular dysfunction from ischemic heart disease is associated with many instances of SCD. Electrophysiologic and autonomic derangements occur in HF, but their contribution to SCD risk is poorly understood.

METHODS

Sudden death risk was assessed in 15 dogs with a healed anterior myocardial infarction (MI) during submaximal exercise and brief acute circumflex ischemia. Left ventricular dysfunction was then induced by repetitive circumflex microembolization until LV ejection fraction reached 35%. Before embolization, six dogs were susceptible to SCD, and nine were resistant.

RESULTS

Baroreflex sensitivity was lower in susceptible dogs (10 ms/mm Hg ± 4 ms/mm Hg vs. 20 ms/mm Hg ± 11 ms/mm Hg, p = 0.04). QT intervals from susceptible dogs were longer after MI (246 ms ± 26 ms susceptible vs. 231 ms ± 20 ms resistant, p < 0.001) and prolonged within eight weeks after LV dysfunction was established (from 246 ms ± 26 ms to 274 ms ± 56 ms, +11%, p < 0.01). Heart rate in susceptible dogs increased during transient ischemia (+20%) and with progressive LV dysfunction (102 beats/min ± 28 beats/min baseline to 154 beats/min ± 7 beats/min LV dysfunction, p = 0.003). All susceptible dogs had spontaneous sustained ventricular tachycardia culminating in SCD. In contrast, QT intervals in resistant dogs prolonged after 24 ± 6 weeks (from 231 ms ± 20 ms to 238 ms ± 15 ms, p < 0.05), and heart rates were unchanged. Only one resistant dog died suddenly with LV dysfunction.

CONCLUSIONS

Depressed vagal and elevated sympathetic control of heart rate coupled with abnormal repolarization are associated with high SCD risk when post-MI LV dysfunction develops.

Abbreviations and Acronyms   BRS = baroreflex sensitivity   ECG = electrocardiogram   HF = heart failure   LV = left ventricle/ventricular   LVEF = left ventricular ejection fraction   MI = myocardial infarction   PVC = premature ventricular contraction   SCD = sudden cardiac death   VF = ventricular fibrillation

This article has been cited by other articles:

				A. Sridhar, Y. Nishijima, D. Terentyev, R. Terentyeva, R. Uelmen, M. Kukielka, I. M. Bonilla, G. A. Robertson, S. Gyorke, G. E. Billman, et al. Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2008; 295(5): R1463 - R1472. [Abstract] [Full Text] [PDF]

				E. Vanoli and P. B. Adamson What does the future hold for the management of chronic heart failure? Eur. Heart J. Suppl., June 1, 2006; 8(suppl_C): C51 - C57. [Abstract] [Full Text] [PDF]

				H. U. Klein and S. Reek "The Older the Broader": Electrogram Characteristics Help Identify the Critical Isthmus During Catheter Ablation of Postinfarct Ventricular Tachycardia J. Am. Coll. Cardiol., August 16, 2005; 46(4): 675 - 677. [Full Text] [PDF]

				B. Nilsson, X. Chen, S. Pehrson, Jør. Hilden, and J. H. Svendsen Increased resting heart rate following radiofrequency catheter ablation for atrial fibrillation Europace, January 1, 2005; 7(5): 415 - 420. [Abstract] [Full Text] [PDF]

				E. Vanoli, S. Bacchini, S. Panigada, F. Pentimalli, and P. B Adamson Experimental models of heart failure Eur. Heart J. Suppl., November 1, 2004; 6(suppl_F): F7 - F15. [Abstract] [Full Text] [PDF]

				P. B. Adamson, A. L. Smith, W. T. Abraham, K. J. Kleckner, R. W. Stadler, A. Shih, M. M. Rhodes, and on behalf of the InSync III Model 8042 and Attain Continuous Autonomic Assessment in Patients With Symptomatic Heart Failure: Prognostic Value of Heart Rate Variability Measured by an Implanted Cardiac Resynchronization Device Circulation, October 19, 2004; 110(16): 2389 - 2394. [Abstract] [Full Text] [PDF]

				M. T. Kearney, J. Nolan, A. J. Lee, P. W. Brooksby, R. Prescott, A. M. Shah, A. G. Zaman, D. L. Eckberg, H.S. Lindsay, P. D. Batin, et al. A prognostic index to predict long-term mortality in patients with mild to moderate chronic heart failure stabilised on angiotensin converting enzyme inhibitors Eur J Heart Fail, August 1, 2003; 5(4): 489 - 497. [Abstract] [Full Text] [PDF]