Endogenous Opioids Do Not Mediate HCl-Induced Myocardial Dysfunction

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. In contrast, restoration of a normal arterial pH was associated with increases in cardiac output, heart rate, stroke volume, and dP/dt to greater than control values, as well as a normalization of systemic vascular resistance. These hemodynamic changes were not attributable to direct effects of naloxone. Herein we suggest that although opioids may exert a small role in mediating the contractile dysfunction that occurs during HC- induced metabolic acidemia, there is no apparent influence of opioids on pump performance. Opioids participate very little in the myocardial dysfunction of this model of metabolic acidemia in lambs.