ANESTHETIC EFFECTS ON THE GLYCEROL MODEL OF RHABDOMYOLYSIS-INDUCED ACUTE-RENAL-FAILURE IN RATS

Isoflurane, the most widely used inhalational anesthetic, releases ino rganic fluoride during its metabolism by the cytochrome P450 system. R ecent experimental data indicate that when cultured proximal tubular c ells are exposed to inorganic fluoride, they become relatively resista nt to myoglobin- and ATP depletion-mediated attack. The present study was undertaken to assess whether isoflurane anesthesia might confer in vivo cytoprotection, possibly by causing renal tubular inorganic fluo ride exposure, thereby mitigating a combined myoglobin/ATP depletion m odel of acute renal failure (glycerol-induced ARF). Rats were injected with hypertonic glycerol (50%; 9 ml/kg, intramuscularly) while underg oing 4 h of isoflurane anesthesia. Glycerol-injected rats anesthetized with a virtually nondefluorinated inhalational anesthetic (desflurane ) or with a nonfluorinated anesthetic (pentobarbital) served as contro ls. The severity of ARF was assessed 24 h later (blood urea nitrogen, plasma creatinine [Cr], and renal histology). Anesthetic effects on ex trarenal injury (plasma creatine phosphokinase, lactate dehydrogenase, and hematocrit levels), acute intrarenal heme loading (cast formation ), and BP during the initiation phase of renal injury (0 to 4 h after glycerol injection) were also assessed. Glycerol induced severe ARF un der pentobarbital anesthesia (Cr, 2.8 +/- 0.3 mg/dl; severe tubular ne crosis). Somewhat worse azotemia, but comparable tubular necrosis, res ulted with desflurane use. Conversely, glycerol plus isoflurane anesth esia induced only mild renal damage (Cr, 0.9 +/- 0.1, minimal tubular necrosis; P < 0.01). This reduction apparently was not due to differen ces in degrees of muscle necrosis, hemolysis, acute renal heme loading , or BP during the initiation phase of ARF, suggesting that a direct r enal mechanism was operative. These results: (I) underscore that diffe ring anesthetics can profoundly alter the expression of experimental r enal injury; (2) raise the intriguing possibility that isoflurane coul d potentially protect surgical/trauma patients from rhabdomyolysis-ind uced ARF; and (3) further support the concept that renal fluoride expo sure may confer proximal tubular cytoprotective effects.