Endogenous opiates modify circulatory control through CNS, cardiac and peripheral vascular actions. We have demonstrated locally mediated myocardial responses to intracoronary opiate peptides or naloxone. The increased contractile function which follows naloxone is eliminated by beta-adrenergic blockade and opiate effects greatest when sympathetic activity is high. In isolated hearts, naloxone enhances the intensity and duration of contractile responses to isoproterenol 100% and 1000% respectively. Our data support the hypothesis that: Endogenous opiates with access to the heart modify myocardial performance locally by altering myocardial adrenergic interactions. My objective is to define clearly this opiate/adrenergic interaction as it applies to the heart and coronary circulation. An isolated heart/lung model is necessary to focus on the heart and to control complicating CNS and vascular reflexes. The studies evaluating HR, LVP, LVdP/dt, cardiac output, coronary blood flow and MVO2, are aimed at: a. how opiates and opiate receptor blockade modify myocardial and coronary responses to norepinephrine b. which adrenergic receptor subtypes participate c. which opiate receptor subtypes are responsible d. do fundamental non-adrenergic cardiac functions change and e. are the release and/or reuptake of norepinephrine altered These studies will further our understanding of normal and pathologic influences of opiate peptides in myocardial and coronary function. They may also help assist in the design of better therapies for the use of catecholamines, opiates and naloxone in cardiac emergencies like heart attack and shock.
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