Effect of lung thromboxane generation on regional blood flow during sheep bypass

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Abstract
Acute pulmonary artery hypertension and an increased plasma concentration of thromboxane [TX]B2, the stable metabolite of the potent vasoconstrictor TXA2, occur within minutes of the onset of venovenous (VV) partial bypass in the awake sheep. To search for systemic vasoconstriction, systemic blood flow distribution was assessed by radioactive microspheres and the changes correlated to alterations in plasma TXB2 and 6-keto-[prostaglandin]F1.alpha. concentration. In 10 control sheep, mean plasma TXB2 concentration increased from 0.39 ng/ml prebypass to .apprx. 1.1 ng/ml at 8 and 16 min of bypass. Despite marked pulmonary vasconstriction with a 3-fold elevated resistance, the blood flow to the heart, brain and kidney were unchanged at 8 and 16 min of bypass. Hepatic vascular resistance increased 2-fold at 8 min of bypass. Indomethacin treatment (10 mg/kg) of 6 sheep blocked the increase of both pulmonary and hepatic vascular resistance and reduced TXB2 levels below 0.1 ng/ml. Thus, VV bypass induces transient and selective vasoconstriction of the lung and liver mediated by vasoconstrictor eicosanoids.