Influence of Norepinephrine and Digitalis on Myocardial Oxygen Consumption in the Newborn Lamb

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Abstract
The relationships between cardiac performance and oxygen usage were explored in 19 newborn lambs (5 hours to 8 days old), and the influence of inotropic stimulation was studied. A preparation was developed to measure coronary sinus flow and myocardial oxygen consumption (MVo2) under controlled hemodynamic conditions. Using a gelatin injection technique, we determined that more than 90% of the measured sinus flow originated from left heart tissue; less than 10% was derived from right ventricular myocardium. Changes in contractility were produced by intravenous infusion of norepinephrine or acetylstrophanthidin. Norepinephrine (1-2.4 µg/min kg-1) or acetylstrophanthidin (5 µg/min kg-1) produced increases in the maximal rate of rise of left ventricular pressure and large reductions in left ventricular enddiastolic pressure, but the changes in MVo2 in lambs with constant aortic blood pressure, cardiac output, and heart rate were minimal. Ventricular function curves demonstrated a significant relationship between end-diastolic pressure and MVo2 (P < 0.01). For a given left ventricular end-diastolic pressure, MVo2 was approximately 3 ml/min 100 g-1 left ventricle greater during the infusion of norepinephrine. Therefore, net changes in MVo2 with inotropic stimulation represented a balance between reciprocal changes in diastolic pressure (and volume) and contractility. The enhanced oxygen cost of increased contractility might be masked by a reduction in heart size (reduced wall stress). Ventricular function was reduced below initial control values following the infusion of norepinephrine in 3 lambs. This reduction correlated with a concomitant reduction in MVo2 and percent extraction but not with a reduction in flow. Lambs that did not show mechanical depression demonstrated no reduction in MVo2. These findings suggest a metabolic basis for catechol dependence which might have special importance for the newborn lamb with its incompletely developed catechol enzyme systems.