MYOCARDIAL BETA-ADRENERGIC-RECEPTOR FUNCTION AND HIGH-ENERGY PHOSPHATES IN BRAIN DEATH-RELATED CARDIAC DYSFUNCTION

Background Cardiac failure remains an important problem after heart transplantation and may be associated with events that occur during brain death (BD) before transplantation. In this study, cardiac function is studied after BD, and biochemical evaluation of myocardial high-energy phosphates and the beta-adrenergic receptor system is presented. Methods and Results The hearts of 17 mongrel dogs (23 to 31 kg) were instrumented with flow probes, micromanometers, and ultrasonic dimension transducers to measure ventricular pressure and volume relationships: In a validated canine BD model, systolic right and left ventricular (RV/LV) function was analyzed by load-insensitive measurements during caval occlusion (preload-recruitable stroke work, PRSW). The beta-adrenergic receptor (BAR) density, adenylate cyclase (AC) activity, and myocardial ATP and creatine phosphate (CP) were measured before and 6 to 7 hours after ED. Results are expressed as mean+/-SEM (*P<.05 versus baseline, paired two-tailed Student's t test). Myocardial function deteriorated significantly from baseline PRSW (RV, 22+/-1 ergx 10(3); LV, 75+/-4 ergx10(3)) by 37+/-10% for the RV (P<.001) and 22+/-7% for the LV (P<.001). BAR density increased from 282+/-42 to 568+/-173 fmol/mg for the RV and from 291+/-64 to 353+/-56 fmol/mg for the LV. Isoproterenol-stimulatcd AC activity was also significantly enhanced after BD. ATP and CP, however, remained unchanged after ED compared with baseline values before BD. Conclusions BD causes significant systolic biventricular dysfunction. The loss of ventricular function after BD was more prominent in the right ventricle and may contribute to early postoperative RV failure in the recipient. These injuries occurred despite BAR system upregulation after ED. Global myocardial ischemia is unlikely, since ATP and CP remained normal before and after BD.