Comparison of Thromboxane Synthetase Inhibitor and Methylprednisolone Effects on Protamine Responses in Dogs

Abstract

Neutralization of heparin anticoagulation by protamine produces catastrophic hemodynamic reactions in some patients. Using a canine model, we tested effects of thromboxane synthetase inhibition (CGS-13080) and glucocorticoid pretreatment on the cardiorespiratory effects of protamine. In control dogs, protamine decreased mean arterial pressure and cardiac output and increased mean pulmonary artery pressure, systemic and pulmonary vascular resistances (SVR, PVR), and airway pressure. Both CGS-13080 and methylprednisolone ameliorated some effects of protamine. CGS-13080 infusion decreased mean pulmonary artery pressure, SVR, and airway pressure after protamine injection relative to controls. Cardiac output and PVR were unaffected by the drug, whereas the decrease in mean arterial pressure was prolonged. Plasma thromboxane A2 metabolite (TXB2) concentrations were lower and prostacyclin metabolite (6-keto PGF1 alpha) concentrations were higher compared with that of controls. These experiments support a role for TXA2 in the response to protamine. Methylprednisolone pretreatment produced larger cardiac output and lower airway pressure after protamine injection compared with controls. Mean arterial pressure was improved, but not significantly. Mean pulmonary artery pressure, SVR, and PVR were not different from that of controls; TXB2 and 6-keto PGF1 alpha were unaffected. The effects of methylprednisolone appear unrelated to arachidonic acid metabolism, as TXB2 and 6-keto PGF1 alpha levels were unaffected.