Local endogenous opiate activity in dog myocardium: receptor blockade with naloxone

The participation of endogenous opiates in myocardial performance and coronary blood flow was investigated. Heart rate, left ventricular contractile force (LVCF), left coronary blood flow (LCBF), and left ventricular oxygen extraction were monitored in anesthetized dogs before and after intracoronary opiate receptor blockade with naloxone. LVCF consistently increased in a dose-dependent fashion following intracoronary naloxone. The increasing LVCF was accompanied by significant increases in LCBF and myocardial oxygen consumption, without changes in heart rate. Rapid onset of responses suggested the presence of endogenous opiates operating locally within the myocardium. Similar effects did not follow right atrial injection of naloxone, ruling out a systemic mechanism. Furthermore, naloxone injected into the isolated left anterior descending artery selectively increased contractile force in that perfusion territory while the adjacent untreated circumflex territory showed no change. The administration of dynorphin into the coronaries produced a depression of LVCF qualitatively consistent with these effects. The effect of dynorphin was subsequently reversed with naloxone. These results support the concept that endogenous opiates participate in the regulation of myocardial function through local mechanisms at the myocardial level.