Stereospecific blocking effects of naloxone against hemodynamic compromise and ventricular dysfunction due to myocardial ischemia and reperfusion.
Endogenous opioid peptides subserve regulatory roles in cardiovascular function and are released upon myocardial ischemia contributing to the development of ischemic arrhythmias and cardiogenic shock, which are reversed by the opioid antagonist naloxone. Since the hallmark of myocardial infarction is the impairment of hemodynamics and ventricular function, we evaluated further if blockade of opioids reverses the ischemia induced hemodynamic compromise, and if the effects are mediated by opioid receptors. Thirty-two mongrel dogs were anesthetized and artificially ventilated. Median thoracotomy was performed, the heart exposed, and the left anterior descending coronary artery isolated for subsequent occlusion and reperfusion. All cardiac parameters were recorded on an Electronics for Medicine recorder through the intracardiac catheters advanced from femoral vessels. Results indicate that naloxone significantly reversed the ischemic and reperfusion induced reduction in aortic, left ventricular and pulmonary arterial pressures, and left ventricular dp/dt. The inactive (+) stereoisomer of naloxone was without effect. These data demonstrate that opioids may have a role in the pathophysiology of myocardial infarction, mediated by opioid receptors, and provide new insight and strategies for the understanding and treatment of ischemic heart disease.
Chen
Y T
YT
Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan.
Lin
C J
CJ
Lee
A Y
AY
Chen
J S
JS
Hwang
D S
DS
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D012770:Shock, Cardiogenic / Q000503:physiopathology; D013237:Stereoisomerism
D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D009270:Naloxone