Thromboxane a2 mediates increased pulmonary microvascular
permeability following intestinal reperfusion .
Turnage, Richard H., John L. Lanoue, Kevin M. Kadesky, Yan Meng,
Stuart I. Myers.
Department of Surgery, University of Texas Southwestern Medical
School, Dallas, TX 76235-9031 and Dallas Veterans Administration
Medical Center, Dallas, TX 75216, Department of Surgery, Temple
University School of Medicine, Philadelphia, PA 19140
APStracts 3:0486A, 1996.
This study examines the hypothesis that intestinal reperfusion (IR)
-induced pulmonary thromboxane (TxA2) release increases local
microvascular permeability and induces pulmonary vasoconstriction.
Sprague-Dawley rats underwent 120 min. of intestinal ischemia and 60
min. of reperfusion (IR). Sham-operated animals served as controls
(SHAM). Following IR or SHAM, the pulmonary vessels were cannulated
and the lungs perfused in vitro with Krebs buffer. Microvascular
permeability was quantitated by determining the filtration
coefficient (Kf) and pulmonary artery (Pa), vein (Pv) and capillary
(Pc) pressures were measured to calculate vascular resistance (Rt).
Following baseline measurements, imidazole (IMID; TxA2 synthetase
inhibitor) or SQ-29,548 (TxA2 receptor antagonist) were added to the
perfusate after which Kf, Pa, Pv, and Pc were again measured. The Kf
of lungs from IR animals was 4 times greater than that of SHAM (p =
0.001) and Rt was 63% greater in the injured group(p = 0.01). Pc of
IR lungs was twice that of controls (5.4 +/- 1.0 vs 2.83 +/- 0.3
mmHg, IR vs SHAM, resp.; p < 0.05). IMID or SQ-29,548 returned
Kf to baseline measurements (p < 0.05) and reduced Rt by 23
and 17%, resp. (p < 0.05). IR-induced increases in Pc were
only slightly reduced by 500 [mu]g/ml IMID (14%; p = 0.05) but
unaffected by lower doses of IMID (5, 50 [mu]g/ml) or SQ-29,548.
These data suggest that IR-induced pulmonary edema is due to both
increased microvascular permeability and increased hydrostatic
pressure and that these changes are due, at least in part, to the
ongoing release of TxA2.
Received 9 July 1996; accepted in final form 30 September 1996.
APS Manuscript Number A631-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996