MECHANICAL UNLOADING BY HETEROTOPIC TRANSPLANTATION OF FAILING RAT HEART REVERSES CARDIAC FUNCTION AND GENE EXPRESSION

Abstract

LVAD support in patients with end-stage heart failure is usually used as a bridge to transplantation. Recently, a few studies have reported functional recovery with LVAD. However, the process of recovery has not been fully understood. Methods. Heart failure was induced in Lewis rats(n = 20) by ligating LAD. After 4 weeks, MI heart was harvested and transplanted to the abdominal vessels of recipient Lewis rat. After LV unloading for 2 weeks, transplanted MI heart was investigated. Normal Lewis rats and MI rats were served as controls. Results. MI heart revealed hypertrophy in heart weight and myocyte diameter. After unloading MI heart by heterotopic transplantation for 2 weeks, hypertrophic heart decreased in weight(MLI.58g vs. unloading MI: 0.91) and myocyte diameter(MI:21.2pm vs. unloading MI: 14.6). Contraction of a posterior papillary muscle was assessed during field stimulation. Papillary muscle function of MI heart was improved after unloading. The mRNA expression were significantly improved after unloading(BNP: Normal:0.21. MI:0.73. unlodingMl:0.3, SERCA2a: Normal:1.6. MI:0.36. unloding MI: 0.86). The levels of β2-adrenergic receptor (AR)-mRNA was increase after unloading (Normal2.2. Mk0.08. unloding MI: 0.31). Conclusions Unloading the failing rat heart can lead to normalize LV hypertrophy and improve papillary muscle function, Ca2+-handling and down regulation of β2-AR. The heterotopic heart transplantation in a small animal can be a model of LV unloading and potentially offers insights into the mechanisms of functional recovery by LVAD.