PRETREATMENT WITH BONE MORPHOGENETIC PROTEIN-7 (BMP7) MIMICS ISCHEMIA PRECONDITIONING (IPC) FOLLOWING INTESTINAL ISCHEMIA/REPERFUSION (IR) INJURY IN THE INTESTINE AND LIVER.

Authors:	Ravi Radhakrishnan, Geetha Radhakrishnan, Hari Radhakrishnan, Hasen Xue, Sasha Adams, Stacey Moore-Olufemi, Matthew Harting, Charles Cox, Bruce Kone
Language:	ENG.
Date:	23-5-2008
Journal:	Shock (Augusta, Ga.) (1073-2322)
Release:	Shock. 2 May 2008
Abstract:	Intestinal ischemia/reperfusion (I/R) injury has been shown to cause intestinal mucosal injury and adversely affect function. Ischemic preconditioning (IPC) has been shown to protect against intestinal I/R injury by reducing polymorphonuclear leukocyte infiltration, intestinal mucosal injury, and liver injury, and preserve intestinal transit. Bone morphogenetic protein 7 (BMP-7) has been shown to protect against I/R injury in the kidney and brain. Recently, microarray analysis has been used to examine the possible IPC candidate pathways. This work revealed that IPC may work through upregulation of BMP-7. The purpose of this study was to examine if pretreatment with BMP-7 would replicate the effects seen with IPC in the intestine and liver after intestinal I/R. Rats were randomized to six groups: sham, I/R (30min of superior mesenteric artery occlusion and 6 h of R), IPC+R (three cycles of superior mesenteric artery occlusion for 4 min and R for 10 min), IPC+I/R, BMP-7+R (100 mum/kg recombinant human BMP-7), or BMP-7+I/R. A duodenal catheter was placed, and 30 min before sacrifice, fluorescein isothiocyanate-Dextran was injected. At sacrifice, dye concentrations were measured to determine intestinal transit. Ileal mucosal injury was determined by histology and myeloperoxidase activity was used as a marker of polymorphonuclear leukocyte infiltration. Serum levels of aspartate aminotransferase were measured at sacrifice to determine liver injury. Pretreatment with BMP-7 significantly improved intestinal transit and significantly decreased intestinal mucosal injury and serum aspartate aminotransferase levels, comparable to animals undergoing IPC. In conclusion, BMP-7 protected against intestinal I/R-induced intestinal and liver injury. Bone morphogenetic protein 7 may be a more logical surrogate to IPC in the prevention of injury in the setting of intestinal I/R.
Copyright:	Shock (Augusta, Ga.) *Department of Surgery, University of Texas-Houston Medical School, Houston; †The Michael E. DeBakey Institute for Comparative Cardiovascular Sciences at Texas A and‡Department of Medicine, University of Texas-Houston Medical School, Houston, Texas.
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