Mechanism responsible for the cardiovascular depressant. Effect of protamine sulfate.

The mechanism of protamine-induced hypotension and bradycardia was investigated in anesthetized, heparinized dogs. Several groups of animals with intact circulation were studied for their responses to protamine under control conditions and following the administration of various pharmacological agents. The parameters observed include femoral arterial pressure (FAP), central venous pressure (CVP), left ventricular pressure (LVP) and its rate of rise (dp/dt), left ventricular contractile element velocity of shortening (Vce), maximal Vce (V max) and cardiac output (CO). Various groups were studied under the following pharmacological conditions: autonomic cholinergic blockade by atropine; alpha and beta adrenergic receptor blockade using phenoxybenzamine and propranolol respectively; ganglionic and adrenal medullary block using hexamethonium, and depletion of endogenous histamine by means of compound 48/80. Another group was placed on total cardiopulmonary bypass thus isolating the heart from the peripheral circulation. The effect of protamine on the vascular tree alone was then observed by monitoring FAP before and after protamine administration. The findings indicate that the cardiovascular effects of protamine are produced by a direct effect on the myocardium and vascular tree.