title: Perioperative matrix metalloproteinase inhibition therapy does not impair wound or anastomotic healing.
abstract: Matrix metalloproteinases (MMPs) catalyze the degradation of collagen and extracellular matrix. They play a role in pathologic states including malignancy, in which they facilitate invasion and metastasis. MMP inhibition has been shown to block neoplastic invasion and improve survival in animal models of malignancy. Concern about the effects of MMP inhibitors on wound and anastomotic healing may limit their potential use in the perioperative period to prevent local and systemic showering of cancer cells from surgical manipulation. We sought to assess the safety of perioperative administration of an MMP inhibitor (BB-94) with respect to skin and bowel healing in a rat model. Absorption of BB-94 was confirmed through high-pressure liquid chromatography and mass spectroscopy of sera from treated animals. Bowel bursting pressure in all animals increased almost 10-fold between 4 and 14 days. Two-way analysis of variance showed no significant difference in bowel bursting pressure between control and treatment animals over time. There was a significant increase in the collagen content of skin specimens of all animals combined between 4 and 28 days. Similarly, all animals showed an increase in bowel collagen between 4 and 28 days. There was no significant difference in skin or bowel collagen concentrations between control and treatment animals over time. Perioperative treatment with MMP inhibition does not impair wound or enteric healing in a rat model of laparotomy and small bowel resection. MMP inhibitors are safe for use as adjuvant therapy after resection for cancer.
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Balcom
authors.forename: Tobias
authors.initials: T
authors.lastname: Keck
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Warshaw
authors.forename: Bozena
authors.initials: B
authors.lastname: Antoniu
authors.forename: Gregory Y
authors.initials: GY
authors.lastname: Lauwers
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-del Castillo
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D003094:Collagen / Q000032:analysis; D007421:Intestine, Small / Q000601:surgery; D007813:Laparotomy; D008297:Male; D023421:Models, Animal; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000737:chemistry; D013876:Thiophenes / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; D003094:Collagen; C080985:batimastat