Thromboxane synthetase inhibition and thromboxane receptor blockade preserve pulmonary and circulatory function in a porcine burn sepsis model

BACKGROUND: Thromboxane A₂ (TxA₂) is a key mediator in the pathophysiology of severe burns and sepsis. This study was performed to assess the potential benefits of TxA₂ synthetase inhibition and TxA₂ receptor blockade in sepsis after severe thermal injury. STUDY DESIGN: Pigs with left atrial, aortic, and pulmonary artery catheters received a 40 percent third-degree burn and, 24 hours later, 100 μg per kg Escherichia coli endotoxin. The antagonist treatment (BM) group was treated with the TxA₂ receptor antagonist BM 13.177, the synthetase treatment (OKY) group with the TxA₂ synthetase inhibitor OKY-046, and the control group received saline solution placebo. Another group without burn or endotoxin was used to assess the side effects of BM 13.177. RESULTS: Both drugs significantly attenuated the changes in pulmonary vascular resistance index, cardiac index, arterial PO₂, shunt, oxygen delivery, and oxygen consumption seen after endotoxin. However, cardiac index was significantly decreased in group BM before endotoxin. In healthy pigs, BM 13.177 decreased cardiac index and oxygen delivery and increased the pulmonary vascular resistance index. CONCLUSIONS: TxA₂ synthetase inhibitors and TxA₂ receptor blockers are potentially useful in sepsis after severe burns. Comparison between drugs was complicated by the adverse effects of the antagonist, and further investigation with other antagonists is needed.