Pharmacologic evidence for the involvement of central and peripheral opioid receptors in the cardioprotective effects of fentanyl.

Abstract

We investigated the involvement of central and peripheral opioid receptors (OR) in the cardioprotective effects of fentanyl (FENT) in a model of myocardial ischemia/reperfusion injury associated with pharmacologically induced sympathetic overactivity in anesthetized rabbits. Central sympathetic stimulation was achieved through intracerebroventricular injection of l-glutamate in animals submitted to 35 min of coronary occlusion followed by 120 min of reperfusion. Rabbits received naloxone HCl intracerebroventricularly or naloxone methiodide IV, a quaternary compound that does not cross the blood-brain barrier, 5 min before FENT treatment (5 or 50 microg/kg, IV). Infarct area was reduced only by FENT 50 (from 51% +/- 2% to 24% +/- 2%). This protective effect was abolished by peripheral (42% +/- 4%), but not central, OR blockade (32% +/- 3%). The number of premature ventricular complexes during the ischemic period (54 +/- 3) was reduced by FENT 50 (19 +/- 7), an effect blunted by central (40 +/- 3) but not peripheral (18 +/- 7) blockade of OR. During reperfusion, the number of premature ventricular complexes (134 +/- 50) was reduced to 9 +/- 5 by FENT 50 and was prevented by central (42 +/- 4) as well as peripheral (20 +/- 11) OR blockade. The mortality rate (50%) and incidence of ventricular tachycardia (55%) were completely abolished by FENT 50. We conclude that fentanyl's effects for limiting myocardial ischemic injury are mediated via peripheral ORs while opioid's antiarrhythmic actions are mediated via central OR agonism.