Differential effects of protamine sulfate on myocyte contractile function with left ventricular failure

This project tested two fundamental hypotheses: 1) Protamine sulfate has a direct and negative effect on myocyte contractile processes; 2) the negative effects of protamine on myocyte contractility will be enhanced in the setting of chronic left ventricular dysfunction.

An increasing number of patients undergoing cardiac and vascular surgical procedures have underlying chronic left ventricular dysfunction. Protamine sulfate is commonly required during these surgical procedures but has been associated with left ventricular dysfunction. However, it is not known whether protamine may have a direct and selective effect on myocyte contractility in the setting of chronic left ventricular dysfunction.

This study examined the direct effects of protamine on isolated myocyte contractile function in 10 control pigs and 10 pigs with dilated cardiomyopathy induced by supraventricular tachycardia (rapid atrial pacing at 240 beats/min for 3 weeks). Myocyte contractile function was measured by videomicroscopy at baseline and with 10, 20, 40 or 80 micrograms/ml of protamine. In a second series of experiments, myocytes were preincubated with protamine and then stimulated with the beta-adrenergic agonist isoproterenol (25 nmol/liter).

In the presence of 20 micrograms/ml of protamine, myocyte contractile function was unaffected in the control group but decreased by 40% from baseline values in the supraventricular tachycardia group. With 10 micrograms/ml of protamine, myocyte beta-adrenergic responsiveness was reduced by 25% in the supraventricular tachycardia group with no change in the control group. In the presence of 40 and 80 micrograms/ml of protamine, myocyte contractile function decreased in both groups. However, 40 micrograms/ml of protamine caused a more pronounced decline in myocyte function and beta-adrenergic responsiveness in the supraventricular tachycardia group.

An increased sensitivity to the depressive effects of protamine on myocyte contractile function and beta-adrenergic responsiveness occurred in this model of chronic left ventricular dysfunction. These results suggest that patients with underlying cardiac disease may have an increased susceptibility to a sudden compromise of left ventricular contractile performance after protamine administration.