Ouabain Effects on Oxygen Physiology in Anemic Lambs

Abstract

ABSTRACT. We studied the effects of anemia and ouabain administration on cardiac function, oxygen physiology, and blood catecholamine levels in nine newborn lambs. We measured oxygen consumption continuously, along with traditional hemodynamic variables. Oxygen transport was calculated. Following baseline measurements, lambs were made anemic (mean hematocrit = 12%) by isovolemic exchange transfusion with Plasmanate, and measurements were repeated. Thereafter ouabain was administered as a 75 pg/kg bolus, followed by 30 min of infusion at a rate of 0.05 pg/kg/min. Measurements were repeated at the conclusion of infusion. Anemia was associated with a heart rate related rise in left ventricular rate of pressure rise, a rise in oxygen consumption, an increase in cardiac output, a decrease in systemic vascular resistance, and a rise in fractional oxygen extraction (oxygen consumption/transport). Following ouabain administration, cardiac output, oxygen consumption, and stroke work fell, but left ventricular rate of pressure rise and the extraction ratio did not change. Serum levels of epinephrine and norepinephrine rose with sustained anemia and ouabain infusion. In this setting, ouabain effects are manifested primarily by alterations in oxygen transport and metabolism rather than by changes in traditional assessments of left ventricular contractile function. (Pediatr Res 21: 447-452, 1987) Abbreviations LV, left ventricle dP/dt, rate of pressure rise PEP, preejection period ET, ejection time VOz, oxygen consumption A-V. arterial-venous SOT, systemic oxygen transport SVR, systemic vascular resistance Cardiac glycosides are used commonly to treat circulatory congestion in infants and children with congenital cardiac defects (1-3). Traditionally, the weight-related doses of digoxin used in immature subjects are higher than those used in adults (4, 5), although the reasons for that practice remain unclear (6-10). Moreover, because the high resting level of myocardial muscle function early in life may not be affected adversely by structural cardiac defects (1 1-14), some have questioned the appropriateness of inotropic therapy for this patient group. Nevertheless, clinical impression and a few selected studies suggest that young subjects with structural cardiac defects benefit from cardiac glycoside therapy (15)(16)(17), although the precise mechanism of the effect has not been established (18)(19)(20).Despite the presence of vigorous myocardial muscle function with many congenital cardiac defects, the congested circulatory state can perturb oxygen transport to the tissues (15, 21). It is possible that in this setting cardiac glycosides may exert their predominant influence on the peripheral supply and demand for oxygen through their effect on the energy requiring sodiumpotassium ATPase pump enzyme system. In the present study we created circulatory conditions characterized by normal to increased myocardial function, yet compromised systemic oxygen transport by inducing anemia in conscious newborn lambs. It was our purp...

Response to Low Cardiac Output: Developmental Differences in Metabolism during Oxygen Deficit and Recovery in Lambs

“…Thus, alveolar ventilation actually decreased to 84% of baseline and respiratory work and O2 consumption would presumably have decreased in proportion. Resting myocardial metabolism in lambs represents about 10% of whole body O2 consumption (22). In both age groups, systolic (and mean) arterial blood pressure decreased relatively more (45% decrease) than heart rate increased (7% increase) during the low cardiac periods.…”

Systemic oxygen transport in patients with congenital heart disease.

“…Reduced SOT secondary to anemia (reduction in oxygen-carrying capacity) has been studied over the short term in dogs24 and lambs. 23 In both studies, cardiac output and V02 rose initially as transport fell. However, at SOT levels under 10 to 13 ml/kg/min (250 to 325 ml/min/m2 assuming a weight of 25 kg corresponds to 1 m2 body surface area), VO2 fell with further reduction in SOT.…”