Pulmonary thromboxane release following intestinal reperfusion.
Microvascular dysfunction is a prominent feature of the lung injury associated with intestinal reperfusion (IR). This study examines the hypothesis that IR induces pulmonary thromboxane A2 (TxA2) release, which contributes to pulmonary microvascular dysfunction. 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 lungs were perfused in vitro with a modified Krebs buffer and ventilated with room air. Eicosanoid levels within the pulmonary venous effluent and bronchoalveolar lavage (BAL) fluid were determined (TxB2, 6-keto-PGF1a, and PGE2). Pulmonary artery pressure (PAP) was measured continuously and expressed as change from baseline in mm Hg. The dominant eicosanoid generated by the lungs in response to IR was TxB2. TxB2 levels in the pulmonary venous effluent of IR lungs were 75% greater than controls (P = 0.005). Similarly, TxB2 levels in the BAL were more than 2.5 times controls (P = 0.001). The change in PAP of lungs from IR animals was significantly greater than that of controls (4.1 +/- 1.5 vs 0.3 +/- 0.54 mm Hg, IR vs SHAM, P = 0.01). The increased PAP associated with IR lungs was prevented by cyclooxygenase inhibition with indomethacin (-1.28 +/- 0.29 mm Hg, P < 0.05) and thromboxane synthetase inhibition with imidazole (-1.75 +/- 0.95 mm Hg, P < 0.05). These experiments support the hypothesis that IR up-regulates endogenous pulmonary TxA2 release. Furthermore, the local release of TxA2 by the lung may contribute to the microvascular dysfunction characteristic of IR-induced lung injury.
Turnage
R H
RH
Department of Surgery, University of Texas Southwestern Medical School at Dallas, USA.
Kadesky
K M
KM
Bartula
L
L
Myers
S I
SI
D000818:Animals; D001794:Blood Pressure; D015232:Dinoprostone / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D013928:Thromboxane A2 / Q000378:metabolism*
D013928:Thromboxane A2; D015232:Dinoprostone