X-Message-Number: 17422
Date: Thu, 30 Aug 2001 05:26:50 -0700 (PDT)
From: Doug Skrecky <>
Subject: isoflurane helps block glycerol toxicity

Title
  Anesthetic effects on the glycerol model of
  rhabdomyolysis-induced acute renal failure in rats.
Source
  Journal of the American Society of Nephrology.  9(2):305-9, 1998 Feb.
Abstract
  Isoflurane, the most widely used inhalational anesthetic, releases inorganic
  fluoride during its metabolism by the cytochrome P450 system. Recent
  experimental data indicate that when cultured proximal tubular cells are
  exposed to inorganic fluoride, they become relatively resistant 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 fluoride exposure, thereby mitigating a
  combined myoglobin/ATP depletion model of acute renal failure
  (glycerol-induced ARF). Rats were injected with hypertonic
  glycerol (50%; 9 ml/kg, intramuscularly) while undergoing 4
  h of isoflurane anesthesia. Glycerol-injected rats
  anesthetized with a virtually nondefluorinated inhalational anesthetic
  (desflurane) or with a nonfluorinated anesthetic (pentobarbital) served as
  controls. The severity of ARF was assessed 24 h later (blood urea nitrogen,
  plasma creatinine [Cr], and renal histology). Anesthetic effects on
  extrarenal 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 under pentobarbital anesthesia
  (Cr, 2.8 +/- 0.3 mg/dl; severe tubular necrosis). Somewhat worse azotemia,
  but comparable tubular necrosis, resulted with desflurane use. Conversely,
  glycerol plus isoflurane anesthesia induced only mild renal
  damage (Cr, 0.9 +/- 0.1, minimal tubular necrosis; P < 0.01). This reduction
  apparently was not due to differences in degrees of muscle necrosis,
  hemolysis, acute renal heme loading, or BP during the initiation phase of
  ARF, suggesting that a direct renal mechanism was operative. These results:
  (1) underscore that differing anesthetics can profoundly alter the expression
  of experimental renal injury; (2) raise the intriguing possibility that
  isoflurane could potentially protect surgical/trauma patients from
  rhabdomyolysis-induced ARF; and (3) further support the
  concept that renal fluoride exposure may confer proximal tubular
  cytoprotective effects.

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