Regional blood flow and pulmonary thromboxane release after sublethal endotoxin infusion in sheep

Fifteen minutes after intravenous Escherichia coli endotoxin (EN) infusion the sheep lung transiently releases into the systemic circulation up to 12 micrograms of thromboxane A2 (TxA2)/min measured by radioimmunoassay as its metabolite thromboxane B2 (TxB2). To determine whether lung thromboxane release alters regional blood flow (RBF) we injected microspheres before and 20, 30, and 100 minutes after EN infusion in 13 awake sheep. In seven untreated control sheep (group 1) pulmonary vascular resistance (PVR) increased threefold at 20 and 30 minutes after EN infusion, coinciding with a large transpulmonary blood concentration gradient of TxB2. There was no measured RBF change to any systemic tissue or organ except the right ventricle at 20 minutes after EN infusion, when blood flow per gram of tissue doubled. In six sheep (group 2) treated with intravenous ibuprofen before EN infusion there was no increase in PVR, plasma TxB2, or blood flow to the right ventricle, and no difference of RBF to any other organ or tissue when compared to group 1. TxA2 is a potent local pulmonary vasoconstrictor but it rapidly hydrolyzes. Its short half-life and the circulatory delay in systemic arterial delivery prevent TxA2 from acting as a circulating vasoconstrictor.