INFLUENCE OF FENTANYL ON THE CHRONOTROPIC RESPONSE OF ISOLATED RABBIT ATRIA TO CHOLINERGIC AND ADRENERGIC STIMULATION

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Abstract
Effects of fentanyl and morphine on chronotropic responses to transmural stimulation applied to the S-A node were studied in isolated rabbit atria. The stimulation caused a frequency-dependent negative chronotropism followed by positive chronotropism, the former abolished by atropine and the latter suppressed by propranolol. The former response at 5 and 20/sec was attenuated in a dose-dependent manner by fentanyl and morphine. Potency ratio of fentanyl to morphine was approx. 50-100. The inhibitory effect of fentanyl and morphine on the response to stimulation of cholinergic nerves was partially prevented or reversed by both naloxone and levallorphan, and also partially reversed by repeated washing of the preparations. Antagonism by naloxone was appreciably greater than that of levallorphan. The negative chronotropic response to transmural stimulation was reduced by levallorphan but not by naloxone. Dose-chronotropic response curves of acetylcholine were unaffected by treatment with fentanyl and morphine. High concentrations of fentanyl and morphine attenuated the response to stimulation of adrenergic nerves, while dose-chronotropic response curves of noradrenaline were not influenced by these narcotics. Naloxone was ineffective in preventing or reversing the effect of fentanyl and morphine. It is therefore concluded that fentanyl and morphine activate opiate receptors located in cholinergic nerve terminals innervating the S-A node, thereby interfering with the release of acetylcholine. Further, it appears that high concentrations of fentanyl and morphine interfere with the release of noradrenaline from postganglionic adrenergic nerve terminals in rabbit atria; however, this action is not related to opiate receptors.
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