INFLUENCE OF NOREPINEPHRINE AND OUABAIN ON CARDIAC MUSCLE MECHANICS DURING HYPOTHERMIA

¹ Department of Pharmacology, University of Oklahoma School of Medicine, Oklahoma City, Oklahoma

Analysis of the mechanics of cardiac contraction in anesthetized, open chest dogs at normal body temperature showed that norepinephrine increased contractile force, rate of contraction (dT/dt), integrated systolic force (ISF), heart rate and blood pressure, and decreased the time for development of peak force and duration of the cardiac cycle in proportion to the dose. When body temperature was lowered to 28-30°C, contractile force, dT/dt and heart rate were decreased, and the time to peak force and durations of the relaxation phase and total cardiac cycle were increased. At 28-30°, a small dose of norepinephrine only stimulated the heart, but 1 µg/kg of norepinephrine caused a triphasic pattern in contractile force, dT/dt, ISF and duration of relaxation characterized by an initial, brief increase, a transient decrease and final prolonged increase. The time to peak force decreased markedly during the first phase, underwent a slight additional shortening in the second phase and returned slowly to control during the third phase. Ouabain given during hypothermia increased force, dT/dt, ISF and blood pressure, but did not alter the other parameters. Norepinephrine after ouabain only decreased contractile force, dT/dt, ISF, time to peak force and duration of the cardiac cycle. The decrease in dT/dt, but not the decrease in the time to peak force, was shown to be the principal cause of the negative inotropic response to norepinephrine in the dog during hypothermia.