Effect of triiodothyronine on graft function in a model of heart transplantation

Abstract

Brain death is associated with neuroendocrine changes that result in impaired metabolism, reduced myocardial energy stores, and deteriorating cardiac function. As a result of these changes, a substantial number of normal human hearts are not considered suitable for transplantation. In the hope of preventing these complications and stabilizing the condition of cardiac donors, we compared the function of transplanted hearts from brain-dead rats that received triiodothyronine (T3) (n = 6) with that of hearts from a group that received a placebo (n = 5). This experiment was designed to be both blinded and randomized. Brain death was achieved by bilateral carotid ligation and inflation of an intracranial balloon. Triiodothyronine or placebo was administered in a blinded, randomized fashion. The brain-dead donors were then supported with conventional techniques for 2 hours after which time heterotopic transplantation was performed using hypothermic preservation and a working heart model. Hemodynamics of the transplanted hearts were assessed 48 hours postoperatively. The hearts from donors that had been pretreated with T3 were found to have a significantly higher (p < 0.005) peak left ventricular pressure than the hearts from the placebo-treated group (137 +/- 17 mm Hg versus 115 +/- 15 mm Hg). Left ventricular end-diastolic pressure was significantly lower (p < 0.01) in the T3-treated group (5.2 +/- 2.2 mm Hg) compared with the placebo-treated group (6.9 +/- 0.5 mm Hg). There was also a significantly higher (p = 0.03) maximal first derivative of left ventricular pressure in the T3-treated group compared with the placebo-treated group (4,876 +/- 1,348 mm Hg/s versus 3,344 +/- 1,016 mm Hg/s). Finally, the cardiac output in the group given T3 was 93 +/- 16 mL/min compared with 61 +/- 22 mL/min in the group given the placebo (p < 0.01). Hearts from brain-dead rats that had received T3 before transplantation showed improved postoperative function. The experimental design of predonation brain death, cold immersion storage, and transplantation in a working heart model should make these data more relevant clinically than those previously reported.