Journal Article

Experimental models of heart failure

Emilio Vanoli, Sara Bacchini, Stefania Panigada, Francesco Pentimalli and Philip B Adamson

in European Heart Journal Supplements

Published on behalf of European Society of Cardiology

Volume 6, issue suppl_F, pages F7-F15
Published in print November 2004 | ISSN: 1520-765X
Published online November 2004 | e-ISSN: 1554-2815 | DOI: http://dx.doi.org/10.1016/j.ehjsup.2004.09.004
Experimental models of heart failure

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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.

Journal Article.  5732 words.  Illustrated.

Subjects: Cardiovascular Medicine

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