GASTROENTEROLOGY M&102:1591-1596 A Ferret Model of Acute Multifocal Gastrointestinal Infarction zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE MARK HUDSON, CHRISTOPHER PIASECKI, ELIZABETH A. SANKEY, ROSALIND SIM, ANDREW J. WAKEFIELD, LINDA J. MORE, AF M. SAWYERR, AMAR P. DHILLON, and ROY E. POUNDER Inflammatory Bowel Disease Study Group, University Departments of Medicine, Histopathology, and Anatomy, Royal Free Hospital School of Medicine, London, England Based on the demonstration of mural granuloma- tous vasculitis in Crohn’s disease, it was hypothe- sized that this vasculitis may account for the dis- continuous pattern of lesions in this condition. Accordingly, the present study investigated the his- tological changes produced by interruption of the submucosal and mucosal microcirculation in the ferret midgut. Two techniques were used. First, up to zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 30 adjacent vasa recta were ligated using micro- surgical techniques; this produced no evidence of ischemic damage. Second, interruption of the sub- mucosal collateral plexus by the i&a-arterial in- jection of styrene microspheres (27-, 50-, or 90-pm diameter) produced acute intestinal mucosal dam- age. A combination of 27- and 90-pm spheres re- sulted in focal mucosal inflammation, necrosis, and ulceration. “ Summit” lesions with normal adjacent mucosa were observed 48 hours after embolization, with evidence of regeneration of the mucosa over- lying the occluded vessels at 72 hours. This model shows that focal gastrointestinal infarction with normal adjacent mucosa can be produced by acute occlusion of submucosal and mucosal arteries. C rohn’s disease is a chronic inflammatory condi- tion principally affecting the gastrointestinal tract, the cause of which is unknown. The disease is characterized morphologically by a patchy distribu- tion of inflammation and mucosal ulceration. This discontinuous pattern of pathology has not been ex- plained by either experimental models of inflamma- tory bowel disease or by prevailing concepts of the pathogenesis of Crohn’s disease.‘*’ We have characterized multifocal granulomatous occlusive microvascular injury in Crohn’s disease, occurring principally within the submucosa and deeper layers of the bowel wall but also in mucosal vessels.3*4 Vasculitis may occur in macroscopically normal bowel in the absence of mucosal ulceration, suggesting that it is an early event in the evolution of the diseases3 We have proposed that ischemia is the consequence of this occlusive vascular lesion with subsequent ulceration of the mucosa supplied by the occluded vessels. The microscopic appearances of mucosal lesions in Crohn’s disease are not those of classical infarc- tion of the intestine, which is characteristically me- diated by occlusion of a large mesenteric vessel.‘” However, it is possible that the macroscopic and mi- croscopic features of intestinal infarction differ ac- cording to both the site of the ischemic insult and the size and nature of the involved vessels. This is rein- forced by the observation that other intestinal dis- eases implicated with an ischemic process do not manifest the histological features of classical infarc- tion.“ ’ The capacity of the mucosa to overcome a localized microvascular occlusion depends largely on the capacity of the submucosal collateral plexus (the main site of collateral circulation in the bowel wa11)*2*13 to overcome the effects of the ischemic in- sult. The purpose of this study was to determine whether experimental interruption of the submuco- sal microvasculature could reproduce a discon- tinuous pattern of inflammation and mucosal ulcer- ation similar to Crohn’s disease. This would not only support the vascular hypothesis of the pathogenesis of Crohn’s disease X* but could also help to explain the basis of the patchy inflammation found in this condition. Materials and Methods The ferret was chosen as the experimental animal for this study because it is a reasonable-sized omnivore with an accessible mesenteric vascular anatomy. Extramural Microvascular Ligation Using microsurgical techniques, nine ferrets un- derwent a laparotomy under general anesthesia (2 L/min 0 1992 by the American Gastmenterological Association 9916-5095/92/$3.99