Pulmonary response to inhibition of thromboxane A2 synthesis during endotoxemia utilizing the inhibitor U63577A

R. A. Gunther, G. J. Smith, J. W. Holcroft

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Pulmonary artery hypertension following endotoxin administration appears to be related to the release of thromboxane A2 (TxA2). We studied inhibition of thromboxane synthesis during endotoxin-induced respiratory distress in chronically instrumented sheep with lung lymph fistulae and vascular catheters. Lymph flow (Q(L) indicates transvascular fluid flux; lymph to plasma (L/P) protein ratio indicates permeability. Nine sheep were utilized in paired experiments with endotoxin alone (2 μg/kg) and endotoxin plus the TxA2 synthesis inhibitor sodium-5-(3'-pyridinylmethyl)-benzofuran-2-carboxylate, U63577A (Upjohn). A bolus (30 mg/kg) of inhibitor was given 30 min. before endotoxin followed by constant infusion (18 mg/kg/hr). The inhibitor significantly reducted TxA2 (measured as TxB2) in both lymph and blood. Q(L) and the L/P ratio were similar between the two groups. The early pulmonary hypertension associated with endotoxin was significantly reduced. However, with the inhibitor a later rise in PA pressure was noted in some sheep despite the marked reduction of TxA2. Two of these sheep died. The results of this study indicate that decreasing TxA2 reduced the initial pulmonary hypotension of endotoxin but may produce late changes leading to greater mortality possibly from shunting endoperoxides into other pathways.

Original languageEnglish (US)
Pages (from-to)No. 8747
JournalFederation Proceedings
Issue number6
StatePublished - 1985

ASJC Scopus subject areas

  • Medicine(all)


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