Myocardial β-Adrenergic Receptor Function and High-Energy Phosphates in Brain Death– Related Cardiac Dysfunction

Abstract

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 β-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 β-adrenergic receptor (BAR) density, adenylate cyclase (AC) activity, and myocardial ATP and creatine phosphate (CP) were measured before and 6 to 7 hours after BD. 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 erg×10 3 ; LV, 75±4 erg×10 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-stimulated AC activity was also significantly enhanced after BD. ATP and CP, however, remained unchanged after BD 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 BD. Global myocardial ischemia is unlikely, since ATP and CP remained normal before and after BD.