Beta-adrenergic receptor antagonism preserves myocardial function after brain death in a porcine model.

BACKGROUND: Cardiac dysfunction after brain death decreases the already limited number of potential donors for cardiac transplantation. Acute beta-adrenergic receptor (betaAR) desensitization after the brain death-associated catecholamine surge is an important mechanism. We hypothesized that acute betaAR antagonism could improve myocardial function after brain death by preserving betaAR signaling.

METHODS: Pigs were randomly assigned to three study groups (n = 5): sham; brain death; and brain death with betaAR antagonist (200 microg/kg/min esmolol), 30 minutes before brain death until 45 minutes after brain death. Functional data were collected for 6 hours after brain death and tissues procured.

RESULTS: Compared with baseline, pre-load recruitable stroke work (PRSW), a pre-load-independent measure of systolic function (21.4 +/- 7.5 vs 43.3 +/- 6.8, slope of regression line during vena caval occlusion, p < 0.001), diastolic function (Tau, 101 +/- 54.7 vs 36.4 +/- 5.4 ms, p = 0.03) and systemic oxygen delivery (151 +/- 79.7 vs 298 +/- 78.7 ml/min, p < 0.001) deteriorated in untreated animals at 6 hours after brain death. In contrast, betaAR antagonist maintained baseline systolic function (PRSW, 37.8 +/- 5.6 vs 38.2 +/- 4.7, slope of regression line during vena caval occlusion, p = 0.92), diastolic function (Tau, 32.6 +/- 5.1 vs 48.5 +/- 28.3 ms, p = 0.57) and oxygen delivery (427 +/- 116 vs 397 +/- 98.8 ml/min, p = 0.36) at 6 hours after brain death. betaAR antagonist preserved betaAR signaling, as demonstrated by similar left ventricular (LV) basal (55.4 +/- 32.8 vs 58.8 +/- 10.9 pmol/mg/min, p = 0.40) and isoproterenol-stimulated (125 +/- 70.5 vs 124 +/- 52.0 pmol/mg/min, p = 0.49) adenylate cyclase activity at 6 hours after brain death, upon comparing betaAR antagonist and sham treatment groups. Both LV basal and isoproterenol-stimulated adenyl cyclase activity were higher with betaAR antagonist (25.9 +/- 4.8 pmol/mg/min, p = 0.03) than with untreated brain death (55.6 +/- 17.3 pmol/mg/min, p = 0.02).

CONCLUSIONS: Beta-adrenergic receptor antagonism before brain death preserves cardiac function by preventing betaAR desensitization. This therapy in potential donors might increase the number of organs available for transplantation.