BACKGROUND: Local complications remain a major problem following low anterior rectal resection (LAR) and are mainly due to anastomotic breakdown. Poor blood supply is a predominant factor causing healing failure. Alprostadil, a prostaglandin derivate, is known to enhance local microcirculation by inducing capillary dilatation and neovascularization. The aim of this study was to investigate the effect and safety of i.v. Alprostadil on the physiology of anastomotic wound healing in the rectum.
METHODS: 48 mongrel dogs underwent LAR using a standardized technique. The animals were randomly assigned to receive 1 ng/kg alprostadil infusions twice daily via a i.v. port system (group A, n=24) or 0.9% NaCl i.v. (group B, n=24). Each group was subdivided into 3 subgroups (n=8) and reoperated upon on days 3, 7 and 14, respectively. Following parameters werde evaluated: tissue oxygenation and microperfusion measured by laserflowmetry (flux) in the anastomotic region, breaking strength, histology, Anti F VIII-immunohistochemistry and hydroxyproline. TGF-ß3 ELISA was performed on peritoneal fluid, portal and central venous blood.
RESULTS: All animals had an uneventful postoperative course, no anastomotic leakage was observed. All animals from group A had significantly higher levels of pO2 and laserflowmetry-flux compared with group B. Differences peaked on day 14, when pO2 was 62.5 mmHg (52-73 mmHg)compared to 50 mmHg (48-52 mmHg) (P<0.05) and flux 43% (41-45%) compared to 23.5% (22-25%) (P<0.05). Bursting pressure showed significantly higher levels from day 7 on (group A 52972.5 N/m2 ± 35 N/m2, group B 29462.5 N/m2 ± 79 N/m2). Mean optical density of Anti F VIII immunostainig revealed slightly elevated levels in group A peaking on day 14 (group A 40 MOD ± 5, group B 16 ± 3). Collagen content and TGF-ß levels did not differ significantly until day 7. However, portal venous TGF-ß3 increased significantly in group A after day 7 (group A 40.2 pg/ml ± 1.2 pg/ml, group B 24.5 pg/ml ± 3.1 pg/ml).
CONCLUSION: Daily i.v. application of Alprostadil seems to have positive effects on anastomotic microcirculation and stability after LAR in the dog model. Due to improved neovascularization local production of TGF-ß3 increases causing pronounced collagen production, which is associated with higher mechanical stability of the anastomotic region.
