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Ann Thorac Surg 1987;44:263-268
© 1987 The Society of Thoracic Surgeons

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Articles

The Myocardial Contractile Responses to Protamine Sulfate and Heparin

University of Ottawa Heart Institute, Ottawa Civic Hospital, Ottawa, Ont, Canada

Accepted for publication February 9, 1987.

^* Address reprint requests to Dr. Hendry, University of Ottawa Heart Institute, Ottawa Civic Hospital, 1053 Carling Ave, Ottawa, Ont, Canada K1Y 4E9.

The administration of protamine sulfate for the reversal of heparin anticoagulation has been associated with adverse hemodynamic changes including hypotension and decreased cardiac output. The possible direct toxic effect of protamine on human right atrial trabeculae contracting isometrically in vitro was studied. Muscles were stimulated to contract at 1 Hz in Tyrode's solution (maintained at 34°C, pH 7.4) into which protamine was continuously added. Following a polynomial regression analysis, a parabolic dose-response curve resulted. The equation was: y = 95.13 + 38.76x – 278.71x² where y = relative developed force and x = concentration of protamine (milligrams per milliliters) (r = 0.82). The estimated concentration of protamine resulting in 50% developed force was 0.48 mg/ml. In a second series of experiments, protamine was added to the bath along with a neutralizing amount of heparin. This resulted in a limited reduction in the fall of relative developed force. Thus, protamine in high concentrations alone or in complex with heparin has a direct toxic effect on human myocardial muscle mechanics, and care is warranted in its clinical use.

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