[Intestinal blood flow alterations in postoperative intraabdominal adhesion formation and the role of Endothelin-1 blockade]. / Ameliyat sonrasi karin içi yapisiklik olusumunda bagirsak kan akimindaki degisiklikler ve Endotelin-1 blogunun rolü

BACKGROUND: The current study was planned to investigate intestinal blood flow alterations and the role of ET-1 receptor blockade in the formation of postoperative intraperitoneal adhesion formation. METHODS: Twenty-eight adult Wistar Albino rats weighing between 250 g and 300 g were divided into four groups. Control group (group 1; n=7) did not undergo any operation. Sham group (group 2; n=7) had only laparotomy. In the adhesion group (group 3; n=7), peritoneal patch (1x1 cm) excision from the right abdominal wall and cecal abrasion were done as "adhesion model operation". One week following this, treatment group (group 4; n=7) received a non-selective ET-1 receptor blocking agent bosentan (30 mg/kg, IP) intra-abdominally, once a day for four days. Intestinal blood flow through the superior mesenteric artery was measured, on postoperative seventh day. Adhesion severity and extension as well as myeloperoxidase activity in the adhesion were calculated. RESULTS: Mean intestinal blood flow significantly increased in adhesion group (81.9+/-5.6 ml/100 g) when compared to group 1 (65.5+/-1.2 ml/100 g). Bosentan caused a significant decrease (44.3+/-6.9 ml/100 g) in intestinal blood flow when compared to group 1 and group 2. Sham group (62.2+/-1 ml/100 g) had similar blood flow level with the control group (65.5+/-1.2 ml/100 g). Adhesion scores were similar in adhesion and Bosentan groups. Sham group had almost no adhesions. Myeloperoxidase activity in adhesion tissue was significantly higher in bosentan group. CONCLUSION: Non-selective ET-1 receptor blockade has no effect on prevention of the formation of intra-abdominal adhesion, but causes a decrease in intestinal blood flow. Adhesion formation increases intestinal blood flow. Adhesion formation is accompanied by increased polymorphonuclear infiltration despite bosentan treatment.

Endothelin-3 induced mesenteric vasoconstriction and PMN infiltration in the rat small intestine: role of endothelin receptors.

The objectives of this study were to characterize endothelin (ET)-3-induced alterations in intestinal hemodynamics and to evaluate whether ET-3 administration alters the tissue levels of polymorphonuclear leukocytes (PMNs) and modulates the epithelial barrier function of the small intestine. ET-3 (100 pmol/kg/min) was infused into the superior mesenteric artery (SMA) for 10 min, and tissue samples were obtained 30 min after terminating the infusion. SMA blood flow was significantly decreased throughout the experiment following ET-3 infusion. Pretreatment with bosentan (ET-A and ET-B receptor antagonist), ET-B receptor antagonist BQ-788 or ET-A receptor antagonist BQ-485 completely inhibited the ET-3-induced decrease in the SMA blood flow. Similar results were obtained from the resistance data, in which ET-3-induced increases in SMA resistance were significantly reduced by all ET receptor antagonists. ET-3 administration significantly elevated tissue MPO activity, blood-to-lumen clearance of (51)Cr-EDTA and caused a marked microscopic damage in the intestinal mucosa. ET-3-induced elevations in tissue PMN infiltration and mucosal damage were significantly inhibited by pretreatments with ET-A or ET-B receptor antagonists. Overall, our data indicate that ET-3 causes microscopic damage, PMN infiltration and mucosal dysfunction in the rat small intestine. In addition, ET-3-induced hemodynamic alterations as well as tissue PMN infiltration and mucosal damage are mediated by both ET-A and ET-B receptors.

Endothelin receptor blockers reduce I/R-induced intestinal mucosal injury: role of blood flow.

The aim of the present study was to assess the role of endothelin (ET) in ischemia-reperfusion (I/R)-induced mucosal injury. Mucosal permeability ((51)Cr-EDTA clearance) and tissue myeloperoxidase (MPO) activity were significantly increased after 30 min of ischemia followed by 30 min of reperfusion. The I/R-induced increases in mucosal permeability and polymorphonuclear leukocyte (PMN) infiltration were significantly attenuated by pretreatments with ET(A) (BQ-485) and/or ET(B) (BQ-788) receptor antagonists. Monoclonal antibody (MAb) directed against intercellular adhesion molecule-1 (ICAM-1; MAb 1A29) and superoxide dismutase (SOD) pretreatments significantly attenuated the increased mucosal permeability and PMN infiltration in a similar manner as with ET receptor antagonists. Superior mesenteric artery blood flow was significantly reduced during the reperfusion period. Both ET receptor antagonists caused a significant rise in blood flow compared with an untreated I/R group. In conclusion, our data suggest that ET(A) and/or ET(B) receptors, ICAM-1, and superoxide play an important role in I/R-induced mucosal dysfunction and PMN infiltration. Furthermore, ET is involved in the pathogenesis of post-reperfusion-induced damage and beneficial effects of ET receptor antagonism are related to an improvement of disturbed blood flow during the reperfusion period.