Heterotopic transplantation as a model to study functional recovery of unloaded failing hearts

Abstract

Objectives: Recent studies have demonstrated cardiac improvement in patients supported with a ventricular assist device, suggesting that reverse remodeling and myocardial recovery are possible. We developed an animal model of cardiac unloading by adapting a heterotopic transplantation technique and used it to examine the pattern of functional recovery in the left ventricle of the failing heart. Methods: Heart failure was induced in adult New Zealand rabbits by coronary artery ligation with subsequent myocardial infarction. Animals undergoing sham operation served as a control group. After 4 weeks or 3 months, failing hearts were transplanted into the necks of recipient rabbits. A left ventricular latex balloon connected to subcutaneous tubing allowed repeated physiologic analysis on days 1 and after transplantation and then every 5 days until day 30. Results: Contractility (left ventricular dP/dtmax) and relaxation (left ventricular dP/dtmin) were significantly lower in transplanted postinfarction hearts as compared to control hearts immediately after transplantation. Both left ventricular dP/dtmax and left ventricular dP/dtmin responses to increased preload and to β-adrenergic stimulation progressively improved to a significantly higher level after 30 days of left ventricular unloading for the hearts that were transplanted 4 weeks after myocardial infarction. However, this functional improvement was not detected in failing hearts transplanted 3 months after infarction. Conclusions: This model of cardiac unloading appears at least partially to mimic conditions of ventricular assist devices. If performed early in the development of heart failure, it permits improvement of contractile dysfunction and restoration of cardiac responsiveness to mechanical and β-adrenergic stimulation. Therefore this model may constitute a novel alternative in the study of reverse remodeling in unloaded failing hearts.