Desensitization of myocardial beta-adrenergic receptors and deterioration of left ventricular function after brain death

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Brain Death / metabolism
  • Brain Death / physiopathology*
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Disease Models, Animal
  • GTP-Binding Proteins / metabolism
  • Isoproterenol / pharmacology
  • Myocardium / metabolism*
  • Radioligand Assay
  • Receptors, Adrenergic, beta / metabolism*
  • Sodium Fluoride / pharmacology
  • Swine
  • Ventricular Function, Left*


  • Receptors, Adrenergic, beta
  • Colforsin
  • Sodium Fluoride
  • Cyclic AMP
  • GTP-Binding Proteins
  • Adenylyl Cyclases
  • Isoproterenol