title: Evaluation of the protective effect of a novel prostacyclin analog on mesenteric circulation following warm ischemia.
abstract: The protective effect of a novel prostacyclin (PGI2) analog, OP-2507, on mesenteric circulation was investigated in a canine warm ischemia model. In 20 mongrel dogs, the entire portion of the intestine supplied by the superior mesenteric artery (SMA) and drained by the superior mesenteric vein (SMV) was completely isolated, maintaining the blood and lymph vessels intact. Sixty or 120 min of complete warm ischemia (WI) of the intestine was induced by clamping SMA and SMV, followed by reperfusion for 120 min. Animals were divided into five groups (each n = 4): group 1, sham operation; group 2, 60 min WI; group 3, 120 min WI; group 4, 60 min WI with PGI2 analog administration; group 5, 120 min WI with PGI2 analog administration. The analog was administered at a rate of 6 micrograms.kg-1.h-1 immediately after laparotomy until the end of the observation period. Mean arterial pressure, SMA blood flow (SMABF), SMV pressure were monitored and total mesenteric vascular resistance (TMVR) was calculated. To evaluate the endothelial activation, endothelin, which is secreted from the endothelium under hypoxic stress, was assayed from blood samples of SMV. None of the animals showed significant changes in mean arterial pressure. In groups 2 and 3, SMABF decreased significantly to less than 60% of preoperative value (15 ml.kg-1.min-1) and TMVR significantly increased from 8.1 and 7.3 mm Hg.ml-1.kg.min before WI to 14.0 and 16.4 mm Hg.ml-1.kg.min after 120 min reperfusion, respectively, resulting in delayed hypoperfusion. In contrast, in groups 4 and 5, SMABF increased to over 100% of preoperative level, while TMVR declined from 7.8 and 8.4 mm Hg.ml-1.kg.min before WI to 6.2 and 6.3 mm Hg.ml-1.kg.min after 120 min reperfusion. After 60 min reperfusion, SMABF and TMVR showed a significant difference between the treated and nontreated groups. Only in group 3, high endothelin concentrations (over 20 pg/ml) were observed even after 120 min reperfusion. It was concluded that the PGI2 analog was able to suppress the endothelial activation and the disturbance of mesenteric circulation caused by WI and reperfusion.
authors.affiliation: Second Department of Surgery, Kyoto University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Mashima
authors.forename: G
authors.initials: G
authors.lastname: Shirakami
authors.forename: A
authors.initials: A
authors.lastname: Mitsuyoshi
authors.forename: M
authors.initials: M
authors.lastname: Nakagami
authors.forename: T
authors.initials: T
authors.lastname: Morimoto
authors.forename: M
authors.initials: M
authors.lastname: Terasaki
authors.forename: K
authors.initials: K
authors.lastname: Nakao
authors.forename: H
authors.initials: H
authors.lastname: Yamabe
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: K
authors.initials: K
authors.lastname: Ozawa
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D016232:Endothelins / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D007422:Intestines / Q000098:blood supply* / Q000473:pathology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D013152:Splanchnic Circulation / Q000187:drug effects*
chemical_list: D016232:Endothelins; C049453:OP 2507; D011464:Epoprostenol