Effects of a thromboxane receptor antagonist (NT-126) and a thromboxane synthase inhibitor (OKY-O46) on protamine-induced circulatory changes in dogs

Abstract

Objective: To examine whether a thromboxane receptor antagonist, NT-126, or a thromboxane synthase inhibitor, OKY-046, prevents circulatory changes caused by protamine reversal of heparin and to evaluate the significance of thromboxane generation in the phenomena. Design: Prospective, randomized, controlled, animal study. Setting: A university research laboratory. Participants: Twenty-four adult mongrel dogs. Interventions: According to the pretreatments, the animals were divided into 3 groups (n = 8 in each): (1) control (normal saline); (2) NT-126, 0.01 mg/kg; and (3) OKY-046, 1 mg/kg. Under general anesthesia, all animals were anticoagulated with intravenous heparin, 200 IU/kg, 5 minutes before the pretreatment. Five minutes after the pretreatment, protamine sulfate, 2 mg/kg, was administered intravenously over 10 seconds. Hemodynamic variables were recorded repeatedly until 60 minutes after the protamine. Plasma thromboxane B2 level was determined at baseline and 10 minutes after protamine injection. Measurements and Main Results: The average values of mean arterial blood pressure and mean pulmonary artery pressure among the 3 groups in each period and values in each group over the study period were not significantly different. There was weak correlation between maximum percent increases in systolic pulmonary artery pressure or maximum percent decreases in systolic arterial blood pressure for 5 minutes after the protamine versus percent increases in plasma thromboxane B2 level. Conclusion: Neither NT-126 nor OKY-046 appears to be effective in preventing protamine-induced circulatory changes in this dog model, suggesting that thromboxane generation alone is not responsible for the phenomena. Copyright © 2000 by W.B. Saunders Company