Desensitization of myocardial β-adrenergic receptors and deterioration of left ventricular function after brain death,☆☆,,★★

https://doi.org/10.1016/S0022-5223(95)70107-9Get rights and content
Under an Elsevier user license
open archive

Abstract

Brain death often results in a series of hemodynamic alterations that complicate the treatment of potential organ donors before transplantation. The deterioration of myocardial performance after brain death has been described; however, the pathophysiologic process of the myocardial dysfunction that occurs after brain death has not been elucidated. This study was designed to analyze the function of the myocardial β-adrenergic receptor and the development of left ventricular dysfunction in a porcine model of experimental brain death. Analysis of the β-receptor included determination of receptor density and adenylate cyclase activity after stimulation independently at the receptor protein, the G protein, and the adenylate cyclase moiety. Myocardial β-receptor density did not change after the induction of brain death. A decrease in stimulated adenylate cyclase activity was observed within the first hour after brain death at the level of the β-receptor, the G protein, and the adenylate cyclase moiety, which suggests the occurrence of rapid desensitization of β-receptor function. Significant deterioration of myocardial performance also occurred within the first hour after brain death, represented by a decrease in preloadrecruitable stroke work compared with the baseline value. The deterioration of myocardial performance after brain death correlates temporally with desensitization of the myocardial β-receptor signal transduction system. The mechanism of impairment appears to be localized to the adenylate cyclase moiety itself. (J T HORAC CARDIOVASC SURG 95;110: 51)

Cited by (0)

From the Departments of Surgery,a Anesthesiology,b and Pharmacology,c Duke University Medical Center, Durham, N.C.

☆☆

Supported in part by American Heart Association Grants in Aid No. 92009270 (D. A. S.) and No. 90011230 (P. V. T).

Address for reprints: Thomas A. D'Amico, MD, Duke University Medical Center, Box 31013, Durham, NC 27710.

★★

12/1/63903