The effect of beta-adrenergic blockade and COX-2 inhibition on healing of colon, muscle, and skin in rats undergoing colonic anastomosis.

摘要

OBJECTIVE: COX inhibitors and beta-adrenergic blockers were recently shown to reduce cancer progression in animal models through various mechanisms. These include the prevention of immune suppression during the critical perioperative period, and the preclusion of direct promoting effects of catecholamines and prostaglandins on malignant tissue growth. To assess the safety of such pharmacological treatments in the context of oncologic surgery, the current study evaluates wound healing efficacy in the skin, muscle, and colon tissues in rats undergoing colonic anastomosis. METHODS: F344 rats were treated daily with a COX-2 inhibitor (etodolac), a beta-adrenergic blocker (propranolol), both drugs or vehicles. All rats underwent skin punch biopsy, and half were also subjected to laparotomy and colonic anastomosis. Tensile strength of the abdominal wall and colonic bursting pressure were assessed on Days 3, 7, and 30 postoperatively, and skin biopsy site healing was scored on Days 2, 4, and 6 postoperatively. RESULTS: None of the drug treatments produced any deleterious effects along the expected course of tissue healing. On Day 30, colon bursting pressure showed an abnormal strengthening in animals undergoing anastomosis compared to non-operated animals, across all drug treatments. This abnormal strengthening was attenuated by etodolac. In the skin, surgery reduced healing rate, irrespective of drug treatments. CONCLUSIONS: Effective doses of etodolac and propranolol caused no negative effects on wound healing processes in rats. The apparent safety of such treatments, together with their potential clinical benefits, suggests the incorporation of these treatments in oncologic patients undergoing curative tumor resection.