D'Amico T A, Meyers C H, Koutlas T C, Peterseim D S, Sabiston D C, Van Trigt P, Schwinn D A
Department of Surgery, Duke University Medical Center, Durham, N.C. 27710, USA.
J Thorac Cardiovasc Surg. 1995 Sep;110(3):746-51. doi: 10.1016/s0022-5223(95)70107-9.
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 beta-adrenergic receptor and the development of left ventricular dysfunction in a porcine model of experimental brain death. Analysis of the beta-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 beta-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 beta-receptor, the G protein, and the adenylate cyclase moiety, which suggests the occurrence of rapid desensitization of beta-receptor function. Significant deterioration of myocardial performance also occurred within the first hour after brain death, represented by a decrease in preload-recruitable stroke work compared with the baseline value. The deterioration of myocardial performance after brain death correlates temporally with desensitization of the myocardial beta-receptor signal transduction system. The mechanism of impairment appears to be localized to the adenylate cyclase moiety itself.
脑死亡常常导致一系列血流动力学改变，这使得潜在器官捐献者在移植前的治疗变得复杂。脑死亡后心肌功能的恶化已有描述；然而，脑死亡后发生的心肌功能障碍的病理生理过程尚未阐明。本研究旨在分析实验性脑死亡猪模型中心肌β - 肾上腺素能受体的功能以及左心室功能障碍的发展情况。对β - 受体的分析包括在受体蛋白、G蛋白和腺苷酸环化酶部分分别独立刺激后测定受体密度和腺苷酸环化酶活性。脑死亡诱导后心肌β - 受体密度未发生变化。在脑死亡后的第一小时内，在β - 受体、G蛋白和腺苷酸环化酶部分水平均观察到刺激后的腺苷酸环化酶活性降低，这提示β - 受体功能发生了快速脱敏。脑死亡后第一小时内心肌功能也出现显著恶化，表现为与基线值相比，预负荷可招募的每搏功降低。脑死亡后心肌功能的恶化在时间上与心肌β - 受体信号转导系统的脱敏相关。损伤机制似乎局限于腺苷酸环化酶部分本身。
