ABSTRACT
BACKGROUND & AIMS: Gap junctions are formed by connexins (Cx), a family of proteins that couple endothelial and smooth muscle cells in systemic vessels. In this context, Cx allow the transmission of signals modulating vascular tone. Recently, vascular Cx have been observed in liver cells implicated in liver blood flow regulation. Here, we investigated the role of Cx in the regulation of intrahepatic vascular tone in cirrhosis. METHODS: Livers of Sprague-Dawley control and cirrhotic (common bile duct ligation-CBDL and CCl4 ) rats were perfused, and concentration-effect curves in response to acetylcholine (ACh) precontracted with methoxamine were obtained in the presence of the specific Cx inhibitor 18-alpha-glycyrrhetinic acid or vehicle. Cx expression was assessed by immunofluorescence, western blot and reverse-transcription polymerase chain reaction in liver tissue, hepatic stellate cells, sinusoidal endothelial cells and hepatocytes isolated from control and cirrhotic rat livers. Cx protein expression was also determined in cirrhotic human tissue. RESULTS: Gap junction blockade markedly attenuated relaxation of hepatic vasculature in response to ACh in control (maximal relaxation, -55 ± 10.5% vs. -95.3 ± 10% with vehicle; P < 0.01) and CBDL rats (50.9 ± 18.5% vs. -18.7 ± 5.5% with vehicle; P = 0.01). Livers from CBDL rats and patients with cirrhosis exhibited Cx overexpression. By contrast, CCl4 -cirrhotic rats did not show attenuated relaxation of hepatic vasculature after blockade and Cx expression was significantly lower than in controls. CONCLUSIONS: Gap junctions may contribute to modulating portal pressure and intrahepatic vascular relaxation. Liver gap junctions may represent a new therapeutic target in cirrhotic portal hypertension.
Subject(s)
Connexins/metabolism , Gap Junctions/metabolism , Liver Circulation , Liver Cirrhosis, Experimental/metabolism , Liver/blood supply , Vasodilation , Acetylcholine/pharmacology , Animals , Carbon Tetrachloride , Common Bile Duct/surgery , Connexins/genetics , Dose-Response Relationship, Drug , Gap Junctions/drug effects , Glycyrrhetinic Acid/analogs & derivatives , Glycyrrhetinic Acid/pharmacology , Humans , Ligation , Liver Circulation/drug effects , Liver Cirrhosis, Experimental/chemically induced , Liver Cirrhosis, Experimental/genetics , Liver Cirrhosis, Experimental/physiopathology , Male , Portal Pressure , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Vasodilation/drug effects , Vasodilator Agents/pharmacologyABSTRACT
BACKGROUND: Laparoscopic treatment of simple acute appendicitis (AA) is a safe procedure; however, there are doubts about its safety in cases of complicated AA. The aim of this study was to determine the differences in results of laparoscopic treatment between cases of complicated versus simple AA. MATERIALS AND METHODS: We prospectively included all patients treated for suspected AA by two surgeons of our service between May 2002 and May 2007. Of 221 patients, 20 were excluded from the study because the laparoscopic approach was not possible; 116 of 201 had uncomplicated AA, 57 complicated AA, 12 gynecologic ethiology, 11 negative appendectomy, and 5 other causes; patients without acute appendicitis were also excluded from the study. In all cases, laparoscopy was the first treatment option. The following variables were considered: mean surgical time, reconversions, emergency readmissions, emergency reinterventions or invasive procedures, mean postoperative hospital stay, and postoperative complications (i.e., infectious or noninfectious). RESULTS: Our results showed statistically significantly worse results, in terms of surgical time, postoperative stay, reconversions, and infectious complications, for patients with complicated versus uncomplicated AA; however, no differences were observed regarding noninfectious complications, emergency readmissions, and emergency reinterventions or invasive procedures. CONCLUSIONS: We consider that laparoscopic treatment of complicated AA may be safely used, despite worse results than in cases of simple AA, since the differences in numbers of severe postoperative complications requiring emergency readmission, reintervention, or invasive procedures were not statistically significant.
