Key result
Intracoronary naloxone augmented and prolonged the myocardial contractile response to isoproterenol, an effect that was eliminated by propranolol pretreatment.
Why the study?
Does naloxone enhance myocardial beta-adrenergic responses to isoproterenol in dog models?
Does naloxone enhance myocardial beta-adrenergic responses to isoproterenol in dog models?
Naloxone enhances myocardial beta-adrenergic activity, suggesting that opiate receptor blockade facilitates adrenergic responses.
Naloxone may facilitate myocardial adrenergic responses; hypothesis-generating in canine models, clinical relevance untested.
Intracoronary injection of naloxone produces rapid local increases in myocardial performance. The role of beta-adrenergic activation in this response was investigated. Naloxone was injected into the left anterior descending artery (LAD) of anesthetized dogs with the adjacent circumflex territory serving as control. Naloxone increased the contractile state locally in the LAD region. Pretreatment with propranolol eliminated the regional inotropic response. An isolated heart-lung model was set up, and isoproterenol dose responses were determined. When repeated after naloxone, contractile (dP/dt) responses to isoproterenol were both augmented and prolonged. In a third study imipramine was used to determine whether naloxone might act by reducing neuronal uptake of the isoproterenol. Imipramine extended the effect of isoproterenol temporally but did not alter the peak response. Adding naloxone increased the peak response to isoproterenol and maintained it above the extended imipramine response. The data support the concept that the blockade of opiate receptors facilitates adrenergic activity mediated by myocardial beta 1-receptors 1) directly through postsynaptic mechanisms, 2) indirectly through beta 2-mediated release of norepinephrine, or 3) via interference with nonneuronal disposal mechanisms.
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Caffrey et al. (1986) studied this question. Naloxone vs. Control territory / baseline was evaluated on Contractile state (dP/dt). Intracoronary naloxone augmented and prolonged the myocardial contractile response to isoproterenol, an effect that was eliminated by propranolol pretreatment.
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