A Weak Negative Inotropic Effect of Protamine Sulfate upon the Isolated Canine Heart Muscle

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Abstract
The direct effect of protamine sulfate on myocardial inotropism was studied using an isolated canine heart muscle preparation. Isometric force (F) was decreased to 87.6 .+-. 1.2% of control values by a concentration of 50 .times. 10-3 g/l protamine, which is about equal to the estimated serum concentration of protamine when administered clinically in doses of 4 mg/kg. The decrease in F was accompanied by a decrease in the maximum velocity of force development (dF/dt) but no change in time to peak force. Administration of the preservative of protamine sulfate did not alter F and dF/dt. Protamine may produce a direct negative inotropic effect, mediated by a decrease in intensity but not by a decrease in duration of the active state.

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