EFFECT OF TRIIODOTHYRONINE ON GRAFT FUNCTION IN A MODEL OF HEART-TRANSPLANTATION

Background. 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 substa ntial number of normal human hearts are not considered suitable for tr ansplantation. In the hope of preventing these complications and stabi lizing the condition of cardiac donors, we compared the function of tr ansplanted hearts from brain-dead rats that received triiodothyronine (T-3) (n = 6) with that of hearts from a group that received a placebo (n = 5). Methods. This experiment was designed to be both blinded and randomized. Brain death was achieved by bilateral carotid ligation an d inflation of an intracranial balloon, Triiodothyronine or placebo wa s administered in a blinded, randomized fashion. The brain-dead donors were then supported with conventional techniques for 2 hours after wh ich time heterotopic transplantation was performed using hypothermic p reservation and a working heart model. Hemodynamics of the transplante d hearts were assessed 48 hours postoperatively. Results. The hearts f rom donors that had been pretreated with T-3 were found to have a sign ificantly higher (p < 0.005) peak left ventricular pressure than the h earts 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 T-3-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 ventr icular pressure in the T-3-treated group compared with the placebo-tre ated group (4,876 +/- 1,348 mm Hg/s versus 3,344 +/- 1,016 mm Hg/s). F inally, the cardiac output in the group given T-3 was 93 +/- 16 mL/min compared with 61 +/- 22 mL/min in the group given the placebo (p < 0. 01). Conclusions. Hearts from brain-dead rats that had received T-3 be fore transplantation showed improved postoperative function. The exper imental 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.