DISASSOCIATION OF POSTISCHEMIC RECOVERY OF RENAL ADENOSINE-TRIPHOSPHATE AND CELLULAR INTEGRITY

Previous studies from our laboratory have demonstrated that postischem ic infusion of thyroxin (T4) will augment the restoration of cellular ATP and enhance the recovery of renal function. It has not been clear, however, whether T4 has a direct effect on mitochondrial ATP synthesi s or an indirect effect by stabilization of the plasma membrane. To di fferentiate these putative effects, rats were subjected to 45 min of r enal ischemia and given either normal saline (0.5 mL) or T4 (20 mug/10 0 g body weight) during the first 15 min of reflow. Cellular ATP level s were assessed by P-31-nuclear magnetic resonance spectroscopy, and r elease of lactate dehydrogenase (LDH) was used as an index of plasma m embrane integrity at 30 and 120 min of reflow. In rats given normal sa line, renal ATP had returned to only 57.9 +/- 1.4% of preischemic valu es at 30 min of reflow and 66.1 +/- 1.4% by 120 min. LDH release was 1 3 +/- 0.89% at 30 min and 14.6 +/- 1.6% at 120 min. In contrast, T4-tr eated animals had ATP levels of 70.2 +/- 2.0% at 30 min and 84.0 +/- 1 .9% at 120 min, whereas LDH release was elevated to values similar to those in normal saline-treated rats, 14.9 +/- 1.5% and 14.4 +/- 0.5% a t 30 min and 120 min, respectively (nonischemic LDH 8.8 +/- 0.8%). The se data suggest that T4 stimulates the recovery of renal ATP by a dire ct effect on synthesis rather than an indirect effect related to globa l improvement in cellular integrity.