Isoflurane pretreatment inhibits lipopolysaccharide-induced inflammation in rats.
BACKGROUND
Previous studies have indicated that volatile anesthetic pretreatment protects cells from inflammation; therefore, the authors hypothesized that pretreatment with isoflurane may attenuate the hemodynamic and pathologic changes to the vasculature that are associated with inflammation.


METHODS
Rats received intravenous lipopolysaccharide or saline placebo with and without pretreatment with isoflurane (1.4% for 30 min immediately before lipopolysaccharide). Mean arterial pressure (MAP) and response to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilators were assessed hourly for 6 h. Tumor necrosis factor-alpha concentrations, arterial blood gases, and vascular histology were also determined.


RESULTS
Lipopolysaccharide decreased MAP and vasodilation to acetylcholine and sodium nitroprusside. Lipopolysaccharide also caused acidosis, endothelial swelling, and endothelial detachment from the smooth muscle. Isoflurane pretreatment prevented the decrease in MAP for 5 h and attenuated the decrease at 6 h. Pretreatment increased the vasodilation to acetylcholine in lipopolysaccharide rats to control concentrations but had no effect on sodium nitroprusside. In control rats, isoflurane pretreatment increased the response to acetylcholine and sodium nitroprusside but had no effect on MAP. Isoflurane pretreatment prevented the acidosis and endothelial damage to mesenteric and aortic vessels, and attenuated the increase in tumor necrosis factor-alpha associated with lipopolysaccharide-induced inflammation.


CONCLUSIONS
Pretreatment with 30 min of isoflurane attenuated the decrease in MAP and endothelium-dependent vasodilation, the acidosis, the increase in tumor necrosis factor-alpha, and the damage to the vascular endothelium associated with lipopolysaccharide-induced inflammation in rats. This study suggests that isoflurane pretreatment may protect the vasculature during inflammation.
Plachinta
Roman V
RV
Department of Anesthesiology. University of Virginia Health System, Charlottesville, Virginia 22908-0710, USA.
Hayes
John K
JK
Cerilli
Lisa A
LA
Rich
George F
GF
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D007530:Isoflurane / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D009569:Nitric Oxide; D007530:Isoflurane