Alterations in beta-adrenergic receptors, adenylate cyclase, and cyclic AMP concentrations during acute myocardial ischemia and reperfusion.
Acute severe myocardial ischemia and evolving myocardial infarction cause neural stimulation, increased levels of circulating catecholamines, and release of catecholamines from storage depots in the left ventricle, with consequent exposure of injured myocardial cells to relatively high concentrations of catecholamines during the transitional period in which myocyte injury becomes progressively more severe. beta-Adrenergic receptor numbers may be increased in the ischemic myocardium within 15-35 minutes of coronary artery occlusion and are associated with intact or enhanced coupling with the adenylate cyclase enzyme and elevated levels of cyclic adenosine monophosphate (AMP); their stimulation may mediate ventricular fibrillation. The administration of beta-adrenergic blockers before or within the first few minutes after coronary artery occlusion prevents or attenuates the development of ventricular fibrillation. beta-Receptor numbers are increased in the ischemic myocardium at 60 minutes of coronary artery occlusion but are uncoupled from the adenylate cyclase enzyme at the level of the G protein and/or catalytic unit. However, with reperfusion after 60 minutes of coronary artery occlusion, the increase in ischemic-region beta-adrenergic receptor numbers persists, and adenylate cyclase responsiveness to beta-receptor stimulation is restored. If a catecholamine is administered, increases in cyclic AMP and activated phosphorylase occur in ischemic-reperfused myocardium. These data indicate that beta-adrenergic mechanisms may play an important role in arrhythmogenesis and may contribute to myocyte injury during severe and intense myocardial ischemia and evolving myocardial infarction.
Thandroyen
F T
FT
Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas.
Muntz
K H
KH
Buja
L M
LM
Willerson
J T
JT
D000208:Acute Disease; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism*; D004594:Electrophysiology; D015425:Myocardial Reperfusion; D009994:Osmolar Concentration; D011943:Receptors, Adrenergic, beta / Q000378:metabolism* / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases