Renal artery clamping itself induces renal ischemia which subsequently causes renal cell injury and can lead to renal failure. The duration of warm ischemia that would be safe for postoperative kidney function during partial nephrectomy remains under investigations. Mitochondria play an important role in pathophysiology of ischemia-reperfusion induced kidney injury, however relation between ischemia time and mitochondrial dysfunction are not fully elucidated. Thus, the effects of renal ischemia (20 min, 40 min and 60 min) on mitochondrial functions were investigated by using in vitro rat ischemia model. Thus, electronmicroscopy showed that at short (20 min) ischemia mitochondria start to swell and the damage increases with the duration of ischemia. In accordance with this, a significant decrease in mitochondrial oxidative phosphorylation capacity was observed already after 20 min of ischemia with both, complex I dependent substrate glutamate/malate (52%) and complex II dependent substrate succinate (44%) which further decreased with the prolonged time of ischemia. The diminished state 3 respiration rate was associated with the decrease in mitochondrial Complex I activity and the release of cytochrome c. Mitochondrial Ca(2+) uptake was diminished by 37-49% after 20-60 min of ischemia and caspase-3 activation increased by 1.15-2.32-fold as compared to control. LDH activity changed closely with increasing time of renal ischemia. In conclusion, even short time (20 min) of warm ischemia in vitro leads to renal mitochondrial injury which increases progressively with the duration of ischemia.
Keywords: Calcium uptake; Caspases; Electronmicroscopy; Ischemia; Kidney mitochondria; Lactate dehydrogenase activity.