Depressed cardiovascular function and altered platelet kinetics following protamine sulfate reversal of heparin activity.

This investigation documented the hemodynamic effects of rapid intravenous and intra-arterial administration of protamine sulfate, altered platelet kinetics associated with intravenous protamine sulfate administration, and a possible method of reducing protamine sulfate-induced hypotension. Thirty-six anesthetized dogs underwent continuous hemodynamic monitoring prior to heparinization (150 U/kg) and for 30 minutes after rapid reversal with protamine sulfate (1.5 mg/kg over 10 seconds). Platelet counts, platelet aggregation, and serum thromboxane B2 levels were also assessed. Intra-arterial protamine sulfate administration caused fewer adverse hemodynamic changes than intravenous administration, including significantly (p less than 0.05) reduced falls in mean arterial pressure (-10 vs. -35 mm Hg), cardiac output (-0.2 vs. -0.6 L/min), femoral artery blood flow (+ 34 vs. -16 ml/min), and superior mesenteric artery flow (+ 107 vs. -48 ml/min). Thrombocytopenia following protamine sulfate administration was the same in the two groups. Marked hypotension accompanying intravenous protamine sulfate administration was completely attenuated by a small dose of protamine sulfate (0.75 mg/kg) administered prior to heparinization. Similarly, the thrombocytopenia caused by intravenous administration was significantly lessened by protamine sulfate pretreatment (74% vs. 23% reduction; p less than 0.01). These observations have important implications for both experimental and clinical use of heparin and protamine sulfate.