Protective Effects of Enalaprilat against Postischernic Renal Failure

Abstract

Prolonged intraoperative renal ischemia requires modalities to reduce the incidence of acute tubular necrosis, but there exists no definitive prophylactic regimen. We studied the effects of enalaprilat, an angiotensin-converting enzyme inhibitor, in an attempt to identify such a protective drug. Thirty-four mongrel dogs underwent 90 min of bilateral renal pedicle clamping. Group I was a control of 6 animals. Group II comprised 10 animals who received 12.5 g iv mannitol 15 min prior to clamping and 1 mg/kg iv furosemide immediately after clamp removal. Group III also comprised 10 animals who received enalaprilat 1 mg/kg iv enalaprilat each 15 min prior to clamp placement. Group IV consisted of 8 dogs, each of which received 12.5 g mannitol and 1 mg/kg iv enalaprilat 15 min prior to clamping and 1 mg/kg iv furosemide immediately upon removal of the clamps. Serum blood urea nitrogen (BUN) and creatinine levels were drawn preoperatively and at 12, 24, 48, and 72 hr postoperatively in each animal. The serum BUN levels in group III were significantly lower than those in group I at all times postoperatively (P < 0.05) and were not significantly different from those of group II at any time postoperatively. Similarly, the serum creatinine levels in group III were significantly lower than those of group I (P < 0.05) and were not significantly different from those in group II at any time postoperatively. Neither the serum BUN nor the serum creatinine levels in group IV were different from those of group I at any time postoperatively. We conclude that intravenous enalaprilat offers significant protection against postischemic renal failure and is as effective as a regimen of mannitol and furosemide. However, the combination of all three offers no protection whatsoever relative to controls.