The mechanisms underlying protamine-induced hypotension and bradycardia were the subject of this investigation. Six groups of dogs with intact circulation were tested in controlled circumstances with various drugs. The following parameters were observed: femoral arterial pressure, central venous pressure, left ventricular pressure and its rate of rise, left ventricular contractile element velocity of shortening, maximal Vce, and cardiac output. The six groups were studied under these pharmacological conditions: ganglionic and adrenal medullary block with hexamethonium chlroide, postganglionic parasympathetic blockade by atropine sulphate, alpha and beta adrenergic receptor block by phenoxybenzamine and propranolol respectively, and depletion of endogenous histamine by compound 48/80 (a condensation product of p-methoxyphenethyl methylamine with formaldehyde). The last group was put on extracorporeal circulation to isolate the vascular tree from the heart. The effect of the drug on this isolated vasculature was observed by recording the femoral arterial pressure. Our findings show that the hypotension and bradycardia are produced by a direct effect of protamine on the myocardium and peripheral vascular system.
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