naloxone and Cardiac-Output--Low

We have examined the effects of morphine in auricular myocardium from non-failing and failing human hearts. In both preparations morphine induced inhibition. These responses were not antagonized by naloxone. Comparison of mean IC30 values obtained in non-failing (3.9 (SEM 0.2) x 10(-8) mol litre-1) and failing (5010 (200) x 10(-8) mol litre-1) hearts indicated that the morphine concentration-response curves were significantly (P < 0.001) shifted to the right in preparations from failing hearts. In addition, a decrease in the maximal response was observed. These data indicate that opioid receptors are not involved in the cardiac effects induced by morphine and that there is a decrease in responses to morphine in the failing heart.

Topics: Adult; Aged; Atrial Function, Right; Cardiac Output, Low; Dose-Response Relationship, Drug; Electric Stimulation; Female; Humans; In Vitro Techniques; Male; Middle Aged; Mitral Valve Insufficiency; Morphine; Myocardial Contraction; Naloxone; Narcotic Antagonists; Narcotics

We evaluated the hypothesis that increased endogenous opioid activity mediates part or all of the left ventricular contractile and pump dysfunction previously demonstrated in HCl-induced metabolic acidemia. Eighteen Western newborn lambs were catheterized and instrumented; pacing wires were sutured to the right atrial appendage; a catheter mounted micromanometer pressure transducer was inserted into the left ventricle; and a 2.5 F thermistor was inserted into the distal abdominal aorta. The lambs were studied 3 days after surgery. Metabolic acidemia was produced with an infusion of 0.5 N HCl into the inferior vena cava. Inhibition of endogenous opioids was achieved with a bolus of 2 mg/kg of intravenous naloxone, which was demonstrated to inhibit morphine sulfate-induced myocardial dysfunction. The effects of opioid inhibition were contrasted with our previously published results after restoration of a normal arterial pH with intravenous sodium bicarbonate. In agreement with our previous study, we found that reducing the arterial pH from 7.41 +/- 0.01 to 6.97 +/- 0.04 was associated with a 45% reduction in cardiac output which resulted from a 50% reduction in stroke volume. These changes in turn were mediated by a 35% reduction in the maximal first derivative of left ventricular pressure and/or a 63% increase in systemic vascular resistance which we used to estimate contractility and afterload, respectively. Left ventricular end diastolic pressure increased during acidemia. Although opioid inhibition produced a consistent increase in the maximal first derivative of left ventricular pressure, this increase was relatively small and was not associated with a significant change in cardiac output, stroke volume, or systemic vascular resistance.

Topics: Acidosis; Animals; Animals, Newborn; Asphyxia Neonatorum; Bradycardia; Cardiac Output, Low; Disease Models, Animal; Endorphins; Heart Ventricles; Humans; Hydrochloric Acid; Infant, Newborn; Naloxone; Sheep; Stroke Volume