Journal of Applied Physiology, Vol 71, Issue 4 1376-1381, Copyright © 1991 by American Physiological Society
Thromboxane synthase inhibition and cardiopulmonary function during endotoxemia in sheep
K. Fujioka, K. Sugi, T. Isago, J. T. Flynn, L. D. Traber, D. N. Herndon and D. L. Traber
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77550.
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 micrograms/kg of Escherichia
coli LPS with (n = 8) and without (n = 8) OKY-046 (10 mg/kg bolus, then 10
micrograms.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 +/- 0.51.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/dtmax) were also reduced.
OKY-046 prevented the decreases of ESPDR and +dP/dtmax. OKY-046 also
attenuated the increased lung lymph flow changes seen with LPS.
