Effects of ulinastatin (urinary trypsin inhibitor) on ATP, intracellular pH, and intracellular sodium transients during ischemia and reperfusion in the rat kidney in vivo

To investigate the effects of ulinastatin on renal ischemia-reperfusion injury, we monitored the dynamic changes in ATP, intracellular pH (pHi), and intracellular sodium (Nai) in rats in vivo. Renal ischemia was induced by clamping the abdominal aorta for 30 min followed by reperfusion for 60 min. Ulinastatin, 50,000 U.kg(-1) (UTI group), or normal saline (NS group) was infused for 30 min before ischemia. (31)P- and double quantum (23)Na-NMR were used to monitor ATP, pHi, and Nai. During ischemia, ATP was rapidly depleted and Nai increased to the same extent in both groups. After 60 min reperfusion, Nai in the NS group was almost restored to the preischemic baseline level (117.2 +/- 7.4% of the baseline value), but the recovery of ATP was incomplete (60.9 +/- 7.7%). The recovery of Nai in the UTI group began earlier than in the NS group with better recovery of ATP. The pHi values showed severe acidosis in the NS group compared with the UTI group during ischemia and reperfusion. As for ultrastructural findings, after 60 min reperfusion, the mitochondria were less swollen and less disorganized with respect to the membrane and the cristae in the UTI group. The transcellular sodium gradient is restored before the ATP level is normalized during postischemic reperfusion. Ulinastatin might protect mitochondrial conformation during ischemia, and facilitate functional recovery of the ionic pump after reperfusion.