Thromboxane synthase inhibition and cardiopulmonary function during endotoxemia in sheep

We studied the cardiopulmonary response to endotoxin (lipopolysaccharide, LPS) in sheep with and without the administration of a thromboxane synthase inhibitor, OKY-046. The animals were instrumented for crystalographic dimension analysis of the left ventricle (LV) and for measurement of LV, aortic, left atrial, and pulmonary arterial pressures and cardiac index, as well as lung lymph flow. They received 1.0 μg/kg of Escherichia coli LPS with (n = 8) and without (n = 8) OKY-046 (10 mg/kg bolus, then 10 μg · kg^-1 · min^-1). OKY-046 prevented the increase of pulmonary arterial pressure and the decrease of cardiac index that occurred during the early phase of endotoxemia. Between 8 and 12 h after LPS, cardiac index increased from 6.8 ± 0.7 to 8.9 ± 0.5 l · min^-1 · m^-2. Concomitantly, the end-systolic pressure-diameter relationship (ESPDR, sensitive myocardial contractility index) significantly decreased from 14.7 ± 0.6 to 7.7 ± 0.7. Other indexes of the LV contractility (+dP/dt(max)) were also reduced. OKY-046 prevented the decreases of ESPDR and +dP/dt(max). OKY-046 also attenuated the increased lung lymph flow changes seen with LPS.