BETA-ADRENOCEPTOR DENSITY IN THE DONOR HEART - A GUIDE TO PROGNOSIS

Background-Failure of the donor (graft) heart is the main cause of mor tality in the first month after orthotopic cardiac transplantation. In a preliminary study marked downregulation of cardiac beta adrenocepto r density was found in apparently normal donor hearts of recipients wh o developed severe cardiac failure soon after implantation. Cardiac be ta adrenoceptors are an important factor in the development of cardiac failure in the human heart. The aim of this study therefore was to de termine whether fatal graft failure in the first month after transplan tation is associated with down-regulation of beta adrenoceptor density in the donor heart. Patients and methods-Right ventricular endomyocar dial biopsy specimens were taken from consecutive adult donor patients immediately before implantation. A previously described radioligand b inding method was used to determine beta adrenoceptor density in conse cutive patients who developed fatal graft failure and died within 1 mo nth of transplantation and in a group of control donors transplanted d uring the same period. Results-Perioperative fatal graft failure devel oped in 13 patients. Forty one specimens from donor hearts that were t ransplanted into recipients who did not develop fatal graft heart fail ure formed the control group. There were no systematic differences in donor or recipient characteristics between the graft heart failure and control groups. In particular donor catecholamine requirement and rec ipient pulmonary vascular resistance did not differ between groups. To tal beta adrenoceptor density was reduced in the fatal graft heart fai lure group compared with that in the controls (13 . 4 (7) fmol/mg v 21 (7) fmol/mg; P < 0 . 01). There was a positive correlation between be ta adrenoceptor density in the donor heart and time to death in the gr aft heart failure group (r(3) = 0 . 3, P < 0 . 05). The beta adrenocep tor binding affinity (Kd) did not differ between the graft failure gro up and the controls (47 (6) pM v 44 (7) pM). Conclusion-The developmen t of peri-operative fatal cardiac failure after orthotopic cardiac tra nsplantation is associated with downregulation of beta adrenoceptors i n the donor heart before implantation.