Cardiac trophic stimuli and the transplanted heart

Both hemodynamic and non-hemodynamic stimuli are recognized as regulators of cardiac growth. The chronic effects of an increase in systolic wall stress on left ventricular (LV) mass in the absence of cardiac sympathetic nerve activity can be assessed in human cardiac transplant recipients. Hypertension develops within several weeks/months after transplantation in patients treated with cyclosporine. Two longitudinal studies have shown that the absolute LV mass remains at control values despite an increase in both blood pressure and body weight. The chronic trophic effects of humoral stimuli on LV mass in the absence of hemodynamic load can be assessed following heterotopic cardiac transplantation into the abdomen of rats, with end to side aorto-aortic anastomosis between the donor and recipient aorta. The transplanted heart functions as a denervated "non-working" Langendorff heart. In these animals, the transplanted heart atrophies by about 30-40% within 5-10 days. Although this atrophy may relate to hemodynamic unloading per se, chronic infusions of methoxamine or isoproterenol can prevent the atrophy. The hemodynamic unloading and/or sympathetic denervation appear to increase the sensitivity for these agonists. The transplanted heart thus offers a unique opportunity to study the interactions of hemodynamic and non-hemodynamic stimuli for cardiac growth.