Pentoxifylline protects splanchnic prostacyclin synthesis during mesenteric ischemia/reperfusion.
This study examines the hypothesis that pentoxifylline protects splanchnic PGI2 synthesis during severe mesenteric ischemia/reperfusion injury. Anesthetized Sprague-Dawley rats (300 grams) were subjected to sham or superior mesenteric artery occlusion for 20 minutes followed by 30 minutes of reperfusion. The ischemia/reperfusion groups received either enteral allopurinol (10 mg/kg) daily for 5 days prior to ischemia, PTX (50 mg/kg) 10 minutes prior to ischemia or carrier. The superior mesenteric artery was cannulated and removed with its intact intestine (SV + SI). The SV + SI was perfused in vitro with oxygenated Krebs buffer. The venous effluent was collected and assayed for release of 6-keto-PGF1 alpha, PGE2 and thromboxane B2 by enzyme immunoassay. Severe mesenteric ischemia/reperfusion decreased SV + SI 6-keto-PGF1 alpha release by 40% compared to the sham group but did not alter release of PGE2 or thromboxane B2. Pretreatment of the animals with PTX and not allopurinol preserved SV + SI 6-keto-PGF1 alpha release at all times of perfusion to a level similar to the sham group. These data showed that severe mesenteric ischemia/reperfusion injury abolished release of endogenous splanchnic PGI2. PTX exerted a protective effect against severe mesenteric ischemia/reperfusion injury by maintaining release of splanchnic PGI2, a potent endogenous splanchnic vasodilator.
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235.
S I
SI
Myers
J W
JW
Horton
R
R
Hernandez
P B
PB
Walker
W G
WG
Vaughan
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D004337:Drug Carriers; D011464:Epoprostenol / Q000096:biosynthesis*; D006439:Hemodynamics; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013152:Splanchnic Circulation
D004337:Drug Carriers; D000493:Allopurinol; D011464:Epoprostenol; D010431:Pentoxifylline