title: Endogenous opioids do not mediate HCl-induced myocardial dysfunction.
abstract: 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.
authors.affiliation: Lillie Frank Abercrombie Section of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: D J
authors.initials: DJ
authors.lastname: Fisher
authors.forename: W J
authors.initials: WJ
authors.lastname: Dreyer
authors.forename: C
authors.initials: C
authors.lastname: Tate
authors.forename: L
authors.initials: L
authors.lastname: Michael
authors.forename: E O
authors.initials: EO
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Entman
mesh_terms: D000138:Acidosis / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000150:complications / Q000503:physiopathology; D001919:Bradycardia / Q000209:etiology* / Q000503:physiopathology; D002303:Cardiac Output, Low / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal / Q000503:physiopathology*; D004723:Endorphins / Q000502:physiology*; D006352:Heart Ventricles; D006801:Humans; D006851:Hydrochloric Acid / Q000633:toxicity; D007231:Infant, Newborn; D009270:Naloxone / Q000494:pharmacology; D012756:Sheep; D013318:Stroke Volume
chemical_list: D004723:Endorphins; D009270:Naloxone; D006851:Hydrochloric Acid