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Delayed recovery of renal regional blood flow in diabetic mice subjected to acute ischemic kidney injury

Departments of Medicine, and Renal Research Institute, New York Medical College, Valhalla, New York; and Department of Physiology and Biophysics, Technion: Israel Institute of Technology, Haifa, Israel

Submitted 10 May 2007 ; accepted in final form 12 September 2007

Ischemic acute kidney injury in experimental diabetes mellitus (DM) is associated with a more severe deterioration in renal function than shown in nondiabetic animals. We evaluated whether the early recovery phase from acute kidney injury is associated with a more prolonged and sustained decrease in renal perfusion in diabetic mice, which could contribute to the impaired recovery of renal function. Perfusion to the renal cortex and medulla was evaluated by laser-Doppler flowmetry in 10- to 12-wk-old anesthetized mice with type 2 DM (db/db), heterozygous mice (db/m), and nondiabetic (control) mice (C57BL/6J). After baseline measurements were obtained, the right renal artery was clampedfor 20 min followed by reperfusion for 60 min. The data demonstrated that, in all three groups studied, the reperfusion phase was characterized by a significant increase in the medullary-to-cortical blood flow ratio. Moreover, during recovery from ischemia, there was a marked prolongation in the time (in min) required to reach peak reperfusion in the cortex (db/db: 20.7 ± 4.0, db/m: 12.92 ± 1.9, C57BL/6J: 9.3 ± 1.3) and the medulla (db/db: 20.8 ± 3.2, db/m: 12.88 ± 1.89, C57BL/6J: 11.2 ± 1.2). Additionally, the slope of the recovery phase was lower in db/db mice (cortex: 61.9 ± 23.1%/min, medulla: 16.3 ± 3.6%/min) than in C57BL/6J mice (cortex: 202.2 ± 41.6%/min, medulla: 42.1 ± 7.2%/min). Our findings indicate that renal ischemia is associated with a redistribution of blood flow from cortex to medulla, not related to DM. Furthermore, renal ischemia in db/db mice results in a marked impairment in reperfusion of the renal cortex and medulla during the early postischemic period.

diabetes mellitus; acute kidney injury; ischemia-reperfusion; laser-Doppler flowmetry