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.

Cardiovascular Effects of Enoximone and Epinephrine on Heparin Reversal With Protamine in Conscious Dogs

“…MPAP was 19 2 4 mm Hg in the enoximone group and 24 2 3 and 21 5 2 mm Hg in the control and epinephrine groups (Table 1). PCWP was slightly lower in the enoximone group than in the other groups (Table 1).…”

The Effect of Inhaled Nitric Oxide on Protamine Sulfate-Induced Hypotension in Dogs

“…그러나 정맥내 주사 시 전신저혈압, 과민성반응, 폐 동맥고혈압, 서맥, 혈소판 감소증, 백혈구감소증 및 저 칼슘혈증 등 다양한 부작용을 일으킴이 실험 동 물 [2][3][4][5][6][7][8][9][10][11][12][13] 및 사람에서 [14][15][16][17] 군간에 유의한 차이는 없었다(Fig. 3).…”