title: Thromboxane A2 mediates increased pulmonary microvascular permeability after intestinal reperfusion.
abstract: This study examines the hypothesis that intestinal reperfusion (IR)-induced pulmonary thromboxane A2 (TxA2) release increases local microvascular permeability and induces pulmonary vasoconstriction. Sprague-Dawley rats underwent 120 min of intestinal ischemia and 60 min of IR. Sham-operated animals (Sham) served as controls. After IR or Sham, the pulmonary vessels were cannulated, and the lungs were perfused in vitro with Krebs buffer. Microvascular permeability was quantitated by determining the filtration coefficient (Kf), and pulmonary arterial (Ppa), venous (Ppv), and capillary (Ppc) pressures were measured to calculate vascular resistance (Rt). After baseline measurements, imidazole (TxA2 synthase inhibitor) or SQ-29,548 (TxA2-receptor antagonist) was added to the perfusate; then Kf, Ppa, Ppv, and Ppc were again measured. The Kf of lungs from IR animals was four 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, respectively; P < 0.05). Imidazole or SQ-29,548 returned Kf to baseline measurements (P < 0.05) and reduced Rt by 23 and 17%, respectively (P < 0.05). IR-induced increases in Pc were only slightly reduced by 500 micrograms/ml imidazole (14%; P = 0.05) but unaffected by lower doses of imidazole (5 or 50 micrograms/ml) or SQ-29,548. These data suggest that IR-induced pulmonary edema is caused by both increased microvascular permeability and increased hydrostatic pressure and that these changes are due, at least in part, to the ongoing release of TxA2.
authors.affiliation: Department of Surgery, University of Texas Southwestern Medical School, Dallas 76235-9031, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Turnage
authors.forename: J L
authors.initials: JL
authors.lastname: LaNoue
authors.forename: K M
authors.initials: KM
authors.lastname: Kadesky
authors.forename: Y
authors.initials: Y
authors.lastname: Meng
authors.forename: S I
authors.initials: SI
authors.lastname: Myers
mesh_terms: D000818:Animals; D007422:Intestines / Q000187:drug effects*; D008297:Male; D010539:Permeability; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000494:pharmacology*
chemical_list: D013928:Thromboxane A2