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Mo1259 Esophagogastric Anastomosis in Rats. Improved Healing by BPC 157 and L-Arginine, Aggravation by L-NAME Zeljko Djakovic, Tomislav Becejac, Vedran Cesarec, Goran Madzarac, Dorian Hirsl, Dominik Malekinusic, Jaksa Vukojevic, Domagoj Drmic, Lovorka Batelja Vuletic, Danijela Kolenc, Dinko Stancic Rokotov, Sven Seiwerth, Predrag Sikiric Aim. Esophagogastric anastomosis in human surgery is part of the surgical treatment of esophageal cancer. Anastomotic leak is responsible for a third of all perioperative deaths. We suggest an enhanced healing of esophagogastric anastomosis, NO-system dependent, with stable gastric pentadecapeptide BPC 157 which improved healing of various intestinal anastomosis and which was proposed as a therapy in ulcerative colitis (Curr Med Chem 2012 ; 19(1):126-32 ; Curr Pharm Des 2011 ; 17(16):1612-32). Also, BPC 157 largely interacts with NO-system (Curr Pharm Des 2014 ; 20(7):1126-35). Methods. Throughout 4 days after esophagogastric anastomosis creation, rats received medication (/kg ip once daily: BPC 157 (10µg, 10ng), L-NAME (5mg), L-arginine (100mg) alone and/or combined). Daily assessment includes damage in stomach (sum of longest diameters, mm), esophagus (esophagitis, scored 0-5), anastomosis (ml H2O before leak), pressure in pyloric sphincter and in esophagus at anastomosis (cmH2O), weight loss (g). The values of 68 - 76 cm H2O for lower esophageal sphincter, and 68 - 74 cm H2O for pyloric sphincter, were considered to be normal as determined before. Results. Esophagogastric anastomosis in controls. As seen at the day 4, we noted progressing stomach damage (8.6±0.3), severe esophagitis (3/4/5), rapid anastomosis leak (6.5±1.3), decrease of pressure, severe in pyloric sphincter (27.2±1.3) as well as less pressure assessed in esophagus at anastomosis (50±1.3) alongside with prominent weight loss (47.5±2.8). BPC 157. By contrast, BPC 157 rats treated with 10µg have almost no gastric lesions (0.2±0.1) or esophagitis (0/0/1) ; anastomosis sustains maximal water volume without leakage (20±1.0) ; higher pressure in pyloric sphincter (57.2±1.6), values in esophagus at anastomosis close to normal values in lower esophageal sphincter, alongside with markedly less weight loss (30.5±1.9)(Means±SD, Min/Med/Max, P ≤0.05, at least vs. control). Rats treated with BPC 157 smaller regimen (10ng daily dose) exhibited similar therapeutic effect. L- arginine. We noted a beneficial effect comparable to that of BPC 157 regimens. L-NAME. By contrast to BPC 157 and L-arginine beneficial effects, L- NAME rats exhibited all parameters of esophagogastric anastomosis course markedly aggravated. Combinations. L-NAME+L-arginine-rats presented control values ; Larginine+BPC 157-rats presented a beneficial effect but no augmentation of the previous separate effects ; L-NAME+BPC 157: BPC 157 completely counteracted L-NAME effects, and maintained its original beneficial effect. L- NAME+L-arginine+BPC 157: BPC 157 presented its original beneficial effect. Conclusions. Failed esophagogastric anastomosis healing appears as a NO-system disturbance, and BPC 157 in interaction with the NO-system markedly improves the healing of the esophagogastric anastomosis. |
