Opioid antagonist modulation of ischaemia-induced ventricular arrhythmias: a peripheral mechanism.
Ventricular arrhythmias are an important cause of death after myocardial ischaemia. Animal studies have generated conflicting data on the potentiating or attenuating effects of opioid agonists and antagonists on cardiac rhythm during acute myocardial ischaemia and coronary artery reperfusion. Whether these effects of opioid antagonists are mediated by central or peripheral nervous system mechanisms remains unclear. We examined (a) the effects of peripheral opioid receptor blockade on ischaemia-induced arrhythmia by using methylnaltrexone (MNTX), a novel quaternary derivative of naltrexone (NTX) that does not cross the blood-brain barrier, and (b) whether MNTX would modulate morphine effects during acute coronary artery ligation and reperfusion in the rabbit. The incidence and severity of cardiac arrhythmias were assessed during 40 min of coronary artery occlusion and reperfusion and summarised in an arrhythmia score (AS). MNTX reduced the incidence of ventricular fibrillation (VF) and arrhythmia score during coronary artery occlusion when compared with vehicle (p < 0.05). Naltrexone reduced the incidence of VF (p < 0.05). Although morphine alone had no significant effects, its coadministration blunted the antiarrhythmic properties of MNTX. The data suggest that blockade of opiate receptors outside the central nervous system may protect against ischaemia-induced arrhythmias.
Murphy
D B
DB
Department of Pharmacology and Therapeutics, University College Cork, Ireland.
Murphy
M B
MB
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000150:complications; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds; D011817:Rabbits
D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone; D009020:Morphine