Hind limb ischemia-reperfusion in the leptin receptor deficient (db/db) mouse

Background. Diabetic patients have high incidence of peripheral vascular disease and limb loss after acute extremity injury. Experiments were designed to test the hypothesis that acute tissue injury in leptin receptor deficient (Db) diabetic (type2) mice would be more severe than in non-diabetic mice. Methods. Db and wild type (Wt) mice were subjected to 3 h of ischemia followed by either 4 or 24: h of reperfusion. (314 IR, 3/24 IR). Muscle analyzed for tissue viability (mitochondrial activity), cytokines (KC-murine equivalent of human IL-8, TNF alpha, IL-6), growth factor, and histological evaluation (neutrophils/uninjured muscle fibers). Tissue perfusion was detected during basal and reperfusion conditions using laser Doppler imaging. Results. Mitochondrial activity and histological evaluation for tissue injury did not differ in the Db versus Wt mice at the time intervals studied. When compared with their respective sham animals, both Db and Wt mice had similarly increased levels of KC, IL-6, and VEGF after 3/24 IR. TNF alpha levels increased in Db but not Wt mice after IR. Although absolute increases in TNFa and KC were higher in Db mice, VEGF levels were actually lower in the Db mice. Conclusion. The patterns of tissue perfusion, cytokines, and growth factors were different in Db versus Wt mice. At the acute time intervals studied, these differences did not correlate with an expected greater degree of acute muscle injury in Db mice. (c) 2007 Elsevier Inc. All rights reserved.