Gastric ischemic conditioning increases neovascularization and reduces inflammation and fibrosis during gastroesophageal anastomotic healing

Abstract

The incidence of anastomotic leak and stricture after esophagectomy remains high. Gastric devascularization followed by delayed esophageal resection has been proposed to minimize these complications. We investigated the effect of ischemic conditioning duration on anastomotic wound healing in an animal model of esophagogastrectomy. North American opossums were randomized to four study groups. Group A underwent immediate resection and gastroesophageal anastomosis. Groups B, C, and D were treated with delayed resection and anastomosis after a gastric ischemic conditioning period of 7, 30, and 90 days, respectively. Gastric conditioning was performed by ligating the left, right, and short gastric vessels. An intraabdominal esophagogastric resection and anastomosis was performed, followed by euthanasia 10 days later. Outcome variables included anastomotic bursting pressure, microvessel concentration, tissue inflammation, and collagen deposition. Twenty-four opossums were randomized to groups A (n = 7), B (n = 8), C (n = 5), and D (n = 4). Subclinical anastomotic leak was discovered at necropsy in 5 animals: 3 in group A, and 1 each in groups B and C (p = 0.295). The anastomotic bursting pressure did not differ significantly between groups (p = 0.545). A 7 day ischemic conditioning time did not produce increased neovascularity (p = 0.900), but animals with a 30 day conditioning time showed significantly increased microvessel counts compared to unconditioned animals (p = 0.016). The degree of inflammation at the healing anastomosis decreased significantly as the ischemic conditioning period increased (p = 0.003). Increasing delay interval was also associated with increased muscularis propria preservation (p = 0.001) and decreased collagen deposition at the healing anastomosis (p = 0.020). Animals treated with 30 days of gastric ischemic conditioning showed significantly increased neovascularity and muscularis propria preservation and decreased inflammation and collagen deposition at the healing anastomosis. These data suggest that an ischemic conditioning period longer than 7 days is required to achieve the desired effect on wound healing.