Heterotopic Transplantation of the Failing Rat Heart as a Model of Left Ventricular Mechanical Unloading Toward Recovery

Abstract

The left ventricular assist device (LVAD) is usually used in patients with end-stage heart failure as a bridge to transplantation. Recently, some studies have reported functional recovery with the use of an LVAD, although the mechanisms responsible for recovery are not fully understood. We investigated the functional recovery of the infarcted, failing rat heart in response to mechanical unloading after heterotopic transplantation. Heart failure was induced in Lewis rats by ligating the left anterior descending artery. After 4 weeks, the infarcted hearts were harvested and heterotopically transplanted. The transplanted infarcted heart was removed after 2 weeks of unloading and examined for hypertrophy and fibrosis, as well as for mRNA levels encoding for brain natriuretic peptide, sarco(endo)plasmic reticulum Ca(2+)-ATPase2a (SERCA2a), and beta1- and beta2-adrenergic receptors. Normal and infarcted rats without transplantation served as control animals. The infarcted heart was hypertrophied as evidenced by an increase in heart weight and myocyte diameter. After unloading the infarcted heart for 2 weeks, there was a decrease in heart weight and myocyte diameter. However, the percentage of myocardial fibrosis increased after unloading. The mRNA expression of brain natriuretic peptide and the beta2-adrenergic receptor significantly improved after mechanical unloading. The levels of SERCA2a mRNA tended to increase after unloading. In conclusion, unloading the failing, infarcted heart can help normalize left ventricular hypertrophy and cardiac gene expression. This unloading model appears to partially mimic the conditions of hemodynamic support with an LVAD in heart failure patients and potentially offers insights into the mechanisms of functional recovery.

MicroRNA: Novel Regulators Involved in the Remodeling and Reverse Remodeling of the Heart

“…Heterotopic heart transplantation was performed in rats in the AAC-HT group (n = 9) to induce LV unloading following a procedure described elsewhere [12, 13]. Briefly, the ascending aorta of the donor heart was anastomosed end to side on the recipient’s abdominal aorta, and the pulmonary artery of the donor was anastomosed end to side on the recipient’s inferior vena cava.…”

Determination of Optimal Duration of Mechanical Unloading for Failing Hearts to Achieve Bridge to Recovery in a Rat Heterotopic Heart Transplantation Model

“…14 In this study, heterotopically transplanted hearts were mechanically unloaded in a manner similar to an LVAD and underwent cardiac atrophy. [15][16][17] We used rat heterotopic heart transplantation as a model for LV unloading to test hypothesis that there exists an "optimal duration" for mechanical unloading of a failing heart to reach peak cardiac recovery of contractile function, histology and cardiac gene expression. This peak point is the best time to test weaning from the LVAD to achieve bridge to recovery.…”

Insulin-like Growth Factor-1 Enhances the Efficacy of Myoblast Transplantation With Its Multiple Functions in the Chronic Myocardial Infarction Rat Model

“…However, we have extensive experience with the use of the MI rat model in our laboratory. 7,16,22 The putative results for the sham-operated group can be reasonably extrapolated. In addition, our scientific interest in this study focused exclusively on in vivo activities of IGF-1 as a potent adjunct for myoblast Tx.…”

“…Mean cardiomyocyte diameter was calculated by measuring 10 cardiomyocytes under microscopy (magnification ϫ400), as described previously. 22 The mean SM-derived myotube diameter was calculated by measuring 10 myotubes each in the engrafted area in the same way.…”