Effects of heparin protamine and heparin-protamine complex on cardiovascular system

ABSTRACT

The cardiovascular effects of heparin and protamine sulphate were studied in the in vitro isolated perfused heart and aortic spiral strips of rabbits and in the in vitro arterial blood pressure and ECG of anesthetized cats. Heparin and protamine sulphate, in therapeutic doses, induced a dose dependent cardioinhibitory effect which was reversible and might be through a direct myocardial depressant action. Combined administration of both drugs showed an effect lesser than the summation effect of each drug separately. Protamine [32-256 ug/ml] and only high concentration of heparin [25.6 units/ml] reduced the response of aortic strip to noradrenaline. The combined effect of both drugs together was lesser than expected. In vivo, I.V. injection of heparin did not produce any change in the arterial blood pressure or ECG of anesthetized cats. But rapid I.V. injection of protamine in periods less than 30 seconds, revealed dose dependent reductions of heart rates and decreased the blood pressure suddenly and transient in only 25% of the cases studied. This drop of blood pressure and negative chromotropic effect occurred even after preheparinization of the cats. These data demonstrate that cardiovascular effects, previously attributed to heparin-protamine complex, are due to heparin and protamine themselves separately and circulating heparin does not aggravate these effects of protamine alone