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.
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D004285:Dogs; D004336:Drug Antagonism; D006439:Hemodynamics / Q000187:drug effects*; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D007700:Kinetics; D010974:Platelet Aggregation / Q000187:drug effects; D011479:Protamines / Q000008:administration & dosage / Q000494:pharmacology*; D013921:Thrombocytopenia / Q000139:chemically induced; D014655:Vascular Resistance / Q000187:drug effects
D011479:Protamines; D006493:Heparin