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

G. Iglesias, S. T. Zeigler, C. W. Lentz, D. L. Traber, D. N. Herndon

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)187-192
Number of pages6
JournalJournal of the American College of Surgeons
Volume179
Issue number2
StatePublished - Jan 1 1994

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ASJC Scopus subject areas

  • Surgery

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