DIRECT EFFECTS OF FENTANYL ON CANINE CORONARY-ARTERY RINGS

The potent opioid fentanyl, is commonly used as a general anesthetic f or coronary artery bypass surgery. Experiments were designed to determ ine the direct effects of fentanyl on unstimulated coronary artery tis sue. Isolated, endothelium denuded canine epicardial rings were suspen ded in physiologic tissue baths. Changes in tension were measured as t he concentration of fentanyl was increased. Fentanyl caused increases in ring tension at concentrations of 10(-6)M-10(-4)M, then caused a de crease in tension at 10(-3)M. Calcium channel blockade by 10(-7)M nife dipine abolished all increases in contractile responses to fentanyl an d prevented the relaxation in tension produced by fentanyl. The fentan yl dose-response curve was unchanged by opioid receptor blockade with 10(-6)M naloxone and by alpha and beta adrenoceptor blockade produced by 10(-6)M prazosin and 10(-6)M propranolol. Muscarinic blockade with 10(-6)M atropine and cyclooxygenase inhibition by 10(-6)M indomethacin attenuated the constrictor response to fentanyl. The opioids alfentan il, sufentanil, morphine, and naloxone all produced a dose-response si milar to fentanyl that varied only in amplitude. These findings indica te that increasing concentrations of the anesthestic opioid fentanyl c an cause biphasic changes in basal canine epicardial coronary artery r ing tension. These responses are calcium dependent and may be characte ristic of other opioid agonists and antagonists.