Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo.
BACKGROUND
Volatile anesthetics protect against cardiac ischemia-reperfusion injury via adenosine triphosphate-dependent potassium channel activation. The authors questioned whether volatile anesthetics can also protect against renal ischemia-reperfusion injury and, if so, whether cellular adenosine triphosphate-dependent potassium channels, antiinflammatory effects of volatile anesthetics, or both are involved.


METHODS
Rats were anesthetized with equipotent doses of volatile anesthetics (desflurane, halothane, isoflurane, or sevoflurane) or injectable anesthetics (pentobarbital or ketamine) and subjected to 45 min of renal ischemia and 3 h of reperfusion during anesthesia.


RESULTS
Rats treated with volatile anesthetics had lower plasma creatinine and reduced renal necrosis 24-72 h after injury compared with rats anesthetized with pentobarbital or ketamine. Twenty-four hours after injury, sevoflurane-, isoflurane-, or halothane-treated rats had creatinine (+/- SD) of 2.3 +/- 0.7 mg/dl (n = 12), 1.8 +/- 0.5 mg/dl (n = 6), and 2.4 +/- 1.2 mg/dl (n = 6), respectively, compared with rats treated with pentobarbital (5.8 +/- 1.2 mg/dl, n = 9) or ketamine (4.6 +/- 1.2 mg/dl, n = 8). Among the volatile anesthetics, desflurane demonstrated the least reduction in plasma creatinine after 24 h (4.1 +/- 0.8 mg/dl, n = 12). Renal cortices from volatile anesthetic-treated rats demonstrated reduced expression of intercellular adhesion molecule 1 protein and messenger RNA as well as messenger RNAs encoding proinflammatory cytokines and chemokines. Volatile anesthetic treatment reduced renal cortex myeloperoxidase activity and reduced nuclear translocation of proinflammatory nuclear factor kappaB. Adenosine triphosphate-dependent potassium channels are not involved in sevoflurane-mediated renal protection because glibenclamide did not block renal protection (creatinine: 2.4 +/- 0.4 mg/dl, n = 3).


CONCLUSIONS
Some volatile anesthetics confer profound protection against renal ischemia-reperfusion injury compared with pentobarbital or ketamine anesthesia by attenuating inflammation. These findings may have significant clinical implications for anesthesiologists regarding the choice of volatile anesthetic agents in patients subjected to perioperative renal ischemia.
Lee
H Thomas
HT
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York, USA. tl128@columbia.edu
Ota-Setlik
Ayuko
A
Fu
Yulei
Y
Nasr
Samih H
SH
Emala
Charles W
CW
D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D015151:Immunoblotting; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007511:Ischemia / Q000517:prevention & control*; D054086:KATP Channels; D007668:Kidney / Q000473:pathology; D007672:Kidney Cortex / Q000201:enzymology; D007674:Kidney Diseases / Q000473:pathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D009195:Peroxidase / Q000378:metabolism; D015221:Potassium Channels / Q000819:agonists; D024661:Potassium Channels, Inwardly Rectifying; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D018685:Anesthetics, Inhalation; D016207:Cytokines; D018836:Inflammation Mediators; D054086:KATP Channels; D016328:NF-kappa B; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C092520:uK-ATP-1 potassium channel; D018799:Intercellular Adhesion Molecule-1; D003404:Creatinine; D009195:Peroxidase