CARDIOVASCULAR FUNCTION, OXYGEN EXTRACTION AND LABILE NUCLEOTIDE CONTENT OF CARDIAC MUSCLE DURING NOREPINEPHRINE-INDUCED DEPRESSION OF DIGITALIZED, HYPOTHERMIC DOG HEART MUSCLE

¹ Department of Pharmacology, University of Oklahoma School of Medicine, Oklahoma City, Oklahoma, and Department of Pharmacology, Emory University, Atlanta, Georgia

In the hypothermic dog heart-lung preparation, norepinephnine causes a triphasic contractile force pattern characterized by an initial, brief increase in contractile force, a transient decrease in contractile force and a final prolonged increase in contractile force. These triphasic changes are reflected in the cardiac output, systolic blood pressure and left atnial pressure, and are similar to those observed in vivo. During hypothermia, ouabain increases contractile force and cardiac output and decreases left atrial pressure. Ouabain also blocks the two stimulant responses to norepinephnine and enhances the depressant response to norepinephrine. These effects of norepinephnine before and after ouabain are not caused by changes in cardiac rhythm, coronary flow, extraction of oxygen, cardiac content of adenosine triphosphate and creatine phosphate or peripheral vascular reactivity. Infusion of norepinephnine in vivo at 38°C only increases force, but at 28-30° causes a triphasic response characterized by a brief increase in force, persistence of the phase of cardiac depression throughout the infusion and development of the third (stimulant) phase only after the infusion is stopped. Infusion of norepinephrine after ouabain causes only cardiac depression. These data suggest that two distinct processes are involved in the responses to norepinephrine during hypothermia, one producing a positive inotropic response and the other a negative inotropic response.