Evidence for reperfusion injury in cortical bone as a function of crush injury ischemia duration: A rabbit bone chamber study

A model for critical limb ischemia was produced by occluding femoral vessel s in 24 rabbits with a pneumatic cuff for 0, 2, 4, or 6 hours. Immediate se quelae and subsequent creeping substitution of cortical bone were observed in vivo using an implanted tibial window, the optical bone chamber implant (with intravital microscopy), and then by light and fluorescence microscopy of fluorochrome-labeled and surface-stained ground sections of retrieved i mplants. Six rabbits were used as controls (0 h) for each ischemia treatmen t, and the animals were monitored for 5 weeks postocclusion. A subpopulatio n of 13 implants was retrieved after euthanization and then histologically assessed for bone necrosis and remodeling. The hypothesis tested was that r eperfusion injury during the 24 h after occluder release (reperfusion phase ), and vessel perfusion/caliber, angiogenesis, and net bone resorption duri ng the 5 subsequent weeks (creeping substitution phase), would exhibit isch emia duration-dependent effects. All animals could bear weight on the affec ted limb to ambulate by 1 week posttreatment. Two-way analysis of variance (ANOVA) comparison of the resulting data confirmed a significant difference between control and ischemia-treated rabbits for: (1) vessel perfusion/rep erfusion; (2) vessel caliber; and (3) net bone resorption. Vascular respons es to 4 vs 6 h of ischemia were not significantly different, but net bone r esorption was strictly ischemia duration-dependent. The conclusion that rep erfusion injury was the mechanism spreading ischemia to more vessels was su pported by a decrease in reperfusion and caliber of vessels, and an increas e in vascular permeability and leukocyte adherence during the reperfusion p hase. It is postulated that reperfusion injury produces a secondary ischemi a that amplifies the occlusion-created primary ischemia and, in the present work, may have been succeeded by progressive episodes of ischemia, similar to the infarction pattern of ischemic hearts. (C) 2001 by Elsevier Science Inc. All rights reserved.