The European Society of Cardiology
Experimental models of heart failure
a Department of Cardiology, IRCCS Policlinico S. Matteo and University of Pavia, Pavia, Italy
b Departments of Physiology, Oklahoma University Health Sciences Center, Oklahoma City, OK, USA
c Department of Medicine Cardiology, Oklahoma University Health Sciences Center, Oklahoma City, OK, USA
* Correspondence: Emilio Vanoli, MD, FESC, Department of Cardiology, IRCCS San Matteo and University of Pavia, Italy. Tel./fax: +39 382529531 (E-mail: evanoli{at}compuserve.com).
Abstract
BACKGROUND: Most successful and reproducible animal models of chronic heart failure (HF) include: increased peripheral resistance, rapid ventricular pacing, arteriovenous shunt, supravalvular stenosis, chronic heart block, repetitive transmyocardial direct current (DC) shock. The main limitation of all these approaches was the lack of stability of the left ventricular (LV) dysfunction.
METHODS: We have described a stable and reproducible animal model of LV dysfunction mediated by ischemic loss of contractive myocardium, which is suitable for chronically studying the complex pathophysiology of HF. This model incorporates conscious dogs with a chronic anterior myocardial infarction (MI). Once the MI is stabilized the progression of the ischemic disease is produced by injecting into the circumflex coronary artery 1–2 cc of latex microspheres to cause embolization of microcirculation. This procedure is repeated 3–5 times over several weeks and, at the end, it results in a spread ischemic damage and a significant loss of ventricular systolic function.
RESULTS: The healed MI results in a depression of heart rate variability and baroreflex sensitivity in a subgroup of dogs. In these dogs the depressed vagal control of the heart is associated with elevated arrhythmic risk. On the contrary in dogs with preserved cardiac reflexes the arrhythmic risk is low. In the high risk group a profound electrophysiological remodelling occurs with the MI and progresses once LV dysfunction is created while the low risk dogs tolerate the embolization procedure with a loss in LV function but without the changes in the cardiac electrical stability.
CONCLUSION: Experimental preparations based on a chronic MI and progression of the ischemic damage toward a chronic LV dysfunction has provided important information concerning autonomic and electrophysiologic alterations associated with sudden cardiac death.
Keywords Experimental; Ischemia; Heart failure