Endogenous opiates modify circulatory control through CNS, cerdiac 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 MV02, are aimed at: a. how opiates and opiate receptor blockade modify myocardial and coronary responses to norepnephrine 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.
| Gu, H; Barron, B A; Gaugl, J F et al. (1993) (+)Naloxone potentiates the inotropic effect of epinephrine in the isolated dog heart. Circ Shock 40:206-11 |
| Barron, B A; Gu, H; Gaugl, J F et al. (1992) Screening for opioids in dog heart. J Mol Cell Cardiol 24:67-77 |
| Gu, H; Barron, B A; Gaugl, J F et al. (1992) Dynorphin, naloxone, and overflow of norepinephrine during cardiac nerve stimulation in dogs. Am J Physiol 263:H153-61 |
| Caffrey, J L; Gu, H; Barron, B A et al. (1991) Enkephalin lowers vascular resistance in dog hindlimb via a peripheral nonlimb site. Am J Physiol 260:H386-92 |
| Caffrey, J L; Hathorne, L F; Carter, G C et al. (1990) Naloxone potentiates contractile responses to epinephrine in isolated canine arteries. Circ Shock 31:317-32 |
| Gu, H; Gaugl, J F; Barron, B A et al. (1990) Naloxone enhances cardiac contractile responses to epinephrine without altering epinephrine uptake from plasma. Circ Shock 32:257-71 |
