Isoflurane improves survival and protects against renal and hepatic injury in murine septic peritonitis.
We have demonstrated that volatile anesthetics reduce inflammation after renal ischemia/reperfusion injury in vivo. As hyperactive uncontrolled inflammation can lead to mortality and morbidity during early sepsis, we questioned whether the volatile anesthetic isoflurane could reduce mortality and protect against sepsis induced renal and hepatic dysfunction. Mice were anesthetized with isoflurane or with pentobarbital and subjected to cecal ligation and puncture (CLP) to induce septic peritonitis. Mice were anesthetized for an additional 3 h after CLP with either isoflurane or pentobarbital. Renal and hepatic function was assessed 24 h later and survival after CLP was assessed for 7 days. To determine if isoflurane protects by reducing inflammation, we quantified renal tubular expression of pro-inflammatory (intercellular adhesion molecule 1, tumor necrosis factor alpha [TNF-alpha], and interleukin [IL] 1beta) messenger RNA with reverse transcriptase-polymerase chain reaction. We also measured the plasma levels of the pro-inflammatory cytokines TNF-alpha, keratinocyte-derived chemokine (KC), and IL-6 and an anti-inflammatory cytokine IL-10. Renal cortical apoptosis was also assessed 24 h after CLP. Twenty-four hours after the septic insult, isoflurane-treated mice had significantly improved renal and hepatic function compared with mice anesthetized with pentobarbital. Renal cortices of isoflurane-treated mice had significantly reduced expression of intercellular adhesion molecule 1, TNF-alpha, and IL-1beta messenger RNA and showed less apoptosis. Isoflurane-treated mice had lower plasma levels of TNF-alpha, KC, and IL-6. Isoflurane-anesthetized mice also had significantly prolonged and increased survival compared with pentobarbital-anesthetized mice. Therefore, isoflurane anesthesia conferred significant protection against renal and hepatic dysfunction and death after septic peritonitis and attenuated renal inflammation and apoptosis compared with pentobarbital anesthesia.
Lee
H Thomas
HT
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032-3784, USA. tl128@columbia.edu
Emala
Charles W
CW
Joo
Jin Deok
JD
Kim
Mihwa
M
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D007530:Isoflurane / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013534:Survival
D018685:Anesthetics, Inhalation; D007530:Isoflurane