Ischemia-Reperfusion Injury of Rat Kidney Relates More to Tubular Than to Microcirculatory Disturbances

Abstract

Several pathophysiological mechanisms have been purported to be involved in the development of acute ischemic renal failure, such as impairment of tubular function and/or of the renal microcirculation. However, it has not been elucidated as yet which of these mechanisms relates to the extent of kidney damage. Besides, little is known about the time course relationship between tubular and microcirculatory disturbances during the development of ischemia-reperfusion injury. We therefore performed intravital videomicroscopy of the proximal tubules as well as the peritubular microcirculation of the rat renal cortex during the first 24 hr of reperfusion after varying lengths of warm ischemia (30 min, 30WI group; 60 min, 60 WI group; 90 min, 90WI group). In a separate group of animals subjected to the same protocol, the survival rate (SR) was determined. The SR in these groups were 100%, 20%, and 0%, respectively. Initially, the tubular and microcirculatory changes (i.e., increased tubular diameter and reduced capillary blood flow) relate well to the length of warm ischemia as well as the SR. At a later stage of reperfusion, however, we observed that peritubular capillary blood flow and tubular diameter recovered more quickly in the 90WI group than in the 30WI and 60WI groups. As a result, these parameters as obtained at 24 hr of reperfusion did not relate anymore to the survival rate. Besides, at this stage a severe loss of integrity of the tubular wall was noted in the 60WI and 90WI groups. These findings suggest that kidney viability is not determined by the extent of recovery of microcirculatory blood flow and/or tubular diameter during early reperfusion, but by the integrity of the tubular wall.