Time-dependent impairment of mitochondrial function after storage and transplantation of rabbit kidneys

Background. The mitochondrial respiratory chain is implicated as a major ta rget of kidney damage after ischemia-reperfusion. This study measures chang es in integrated mitochondrial function and in the activity of enzymes of t he respiratory chain after cold storage and transplantation-reperfusion in vivo. Methods. Mitochondrial oxygen consumption and activities of respiratory cha in enzymes and citrate synthase were measured in cortical mitochondria isol ated from rabbit kidneys after 1-48 hr of cold ischemia with or without tra nsplantation-reperfusion. Results. State 4 mitochondrial oxygen consumption was significantly increas ed after 48 hr of ischemia or 24-48 hr of ischemia with transplantation. Pr olonged (24 or 48 hr) ischemic storage with and without transplantation cau sed a significant decrease in state 3 oxygen consumption, as did transplant ation after 1, 24, and 48 hr of cold storage. Complex I and complex II-III activity decreased after 24 or 48 hr of ischemia, with transplantation havi ng little additional effect. Complex IV activity was significantly decrease d after 48 hr of ischemia, this decrease being exacerbated by transplantati on-reperfusion. Complex V activity decreased significantly after 1 hr of is chemia and continued to decrease after 24-48 hr of ischemia. Transplantatio n after 1-24 hr (but not 48 hr) of ischemia resulted in partial recovery of complex V activity. Citrate synthase activity was decreased significantly only after 48 hr of:ischemia and reperfusion, consistent with the loss of m itochondrial membrane integrity seen in electron micrographs of the transpl anted 48-hr group. Conclusions. These data suggest that individual rabbit kidney mitochondrial complexes have different susceptibilities to cold ischemic and reperfusion damage.