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

The direct effect of protamine sulfate upon 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 × 10−3 g/L protamine, which is approximately 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 alteration in time to peak force. Administration of the preservative of protamine sulfate did not alter F and dF/dt. This suggests that protamine produces a direct negative inotropic effect, mediated by a decrease in intensity but not by a decrease in duration of the active state.