Comparative Study for Preventive Effects of Intra-Abdominal Adhesion Using Cyclo-Oxygenase-2 Enzyme (COX-2) Inhibitor, Low Molecular Weight Heparin (LMWH), and Synthetic Barrier

PURPOSE: Postoperative adhesion is the most frequent complication of abdominal surgery. Therefore, we investigated the individual effects of synthetic barrier [hyaluronic acid/carboxymethylcellulose (HA/CMC)] and pharmacologic agents [low molecular weight heparin (LMWH) cyclo-oxygenase-2 inhibitor (COX-2 inhibitor)] using animal model of intra-abdominal adhesion. MATERIALS AND METHODS: The cecum was rubbed with sterile alcohol wet gauze until subserosal haemorrhage and punctate bleeding developed under the general anesthesia. Five animal groups were prepared using the film HA/CMC, gel HA/CMC, LMWH and COX-2 inhibitor. RESULTS: The grade of adhesion by modified Leach method for group I (control), II (film type HA/CMC), III (gel type HA/CMC), IV (LMWH) and V (COX-2 inhibitor) were 5.35+/-1.8, 6.15+/-1.3, 4.23+/-2.6, 5.05+/-0.7 and 5.50+/-0.9, respectively. Group III showed the least grade of adhesion and it is statistically significant in adhesion formation (p=0.028). The numbers of lymphocytes were significantly low in group III and group V compared to the control group (lymphocyte: p=0.004). The mast cell counts were generally low except for the control group (I: 1.05, II: 0.35, III: 0.38, IV: 0.20, V: 0.37), however, it was not statistically significant (p=0.066). CONCLUSION: The gel barriers were shown to be partly efficient in inhibiting the formation of postoperative adhesions and might provide an option for abdominal surgery to reduce postoperative adhesions. The LMWH and COX-2 inhibitor had been known for their inhibitor effect of fibrin formation and anti-angiogenic/anti-fibroblastic activity, respectively. However, their preventive effects of adhesion and fibrosis were found to be obscure.

Antagonista de receptores de neurokinina tipo 1 versus ácido hialurónico/carboximetilcelulosa en la prevención de adherencias peritoneales postoperatorias: estudio experimental en modelo animal / Neurokinin 1 receptor antagonist versus hyaluronic acid-carboxymethylcellulose in the prevention of postoperative peritoneal adhesions: experimental study in biomodels

La actividad fibrinolítica juega un papel fundamental en el desarrollo de las adherencias peritoneales (AP), y se conoce que la sustancia P al actuar sobre receptores de neurokinina tipo 1 a nivel peritoneal, disminuyen la fibrinólisis, favoreciendo la formación de las mismas. La efectividad de antagonistas de estos receptores como tratamiento preventivo de AP, ha sido evaluada, obteniendose resultados favorables. Comparar la efectividad del tratamiento intraperitoneal con antagonista de receptores 1 de neurokinina (NK-RIA) versus gel de ácido hialurónico/carboximetilcelulosa (AH/CMC) en la prevención de AP en modelo animal. A 60 ratas Wistar se les practicó cirugía formadora de AP y fueron distribuidas de forma aleatoria en 3 grupos, un grupo que recibió aprepitant (NK_RIA), otro recibió gel de AH/CMC y un grupo control. Los animales fueron sacrificados a los 7 ó 14 días, y se evaluó el número, severidad e histopatología de las AP. Tanto el NK-RIA como el AC/CMC disminuyeron el número (40% y 38% respectivamente) y severidad de las AP (p=0,001 y p=0,029 rerspectivamente) en relación al grupo control, sin diferencias estadísticas entre ellos (p=0,806). El grupo de NK-RIA presentó menos AP en órganos no manipulados durante la cirugía en relación a los otros 2 grupos. Ambos tratamientos presentaron menor grado de fibrosis que el control, sin embargo el grupo de NK-RIA tuvo menor inflamación (P=0,005) y proliferación vascular (P=0,047) que el AH/CMC. El NK-RIA tiene alta eficacia previendo la formación de AP, equiparable a la gel de AH/CMC.

The fibrinolytic activity play an important role in the peritoneal adhesions (PA) development. It’s well known that of substance P decreased the fibrinolysis by binding the neurokinin-1 receptor, improving the PA formation. Lot of investigation have evaluated the efficacy in PA prevention of antagonist of these receptors, with very good result. To compare the effectivences of intraperitoneal treatment with a neurokin-1 receptor antagonist (NK-RIA) versus hyaluronic acid/carboxymethylcellulose (HA/CMC) gel, in peritoneal adhesion prevention in animal model. In 60 male Wistar rats, PA were induced, and then randomly assigned to 3 groups. A group treated with aprepitant (NK-RIA), a second group treated with HH/CMC and a control group. The animals were killed at 7 or 14 postoperative day, and the number, severity and histopathology of PA were evaluated. NK-RIA and HA/CMC decreased the number (40% and 38% respectively) and severity (p=0,001 and p=0,029 respectively) of PA when compare to control group. The NKRIA group had less PA in no manipulated organs in surgery that the others 2 groups. Both treatments presented less fibrosis that control, however the NK-RIA group presented less inflammation (p=0,005) and vascular proliferation (p=0,047) than HA/CMC group. The NK-RIA is as effective as HC/CMC in preventing PA.