Isoflurane Improves Survival and Protects Against Renal and Hepatic Injury in Murine Septic Peritonitis

Abstract

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.

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

“…Immunohistochemistry for huA 1 ARs was performed as described below. Finally, total RNA was extracted from renal cortices or liver and we performed reverse transcription-PCR assays for EGFP-huA 1 AR, EGFP and mouse GAPDH as described previously 14,17,18 (Table 1). The EGFP-huA 1 AR primer was designed with a sense primer that would anneal in the extreme 5 0 end of the A 1 AR portion of the construct, whereas the anti-sense primer anneals to the extreme 3 0 end of the EGFP portion.…”

Insight into the beneficial immunomodulatory mechanism of the sevoflurane metabolite hexafluoro-2-propanol in a rat model of endotoxaemia

“…The improved outcome is accompanied by an altered immune response resulting in attenuation of the inflammatory response and tissue damage [6][7][8][9]. In recent work, the volatile anaesthetic sevoflurane has been shown to improve survival in septic peritonitis in mice when applied as brief conditioning [10,11], and has been discussed as an additional supportive treatment modality in sepsis [7].…”

Isoflurane Prevents Acute Lung Injury Through ADP-Mediated Platelet Inhibition

“…Although most of the protective effects of isoflurane in sepsis 17,18 and ischemia/ reperfusion 8 injuries have been attributed to the neutrophil, the effect on the platelet has been largely overlooked. The emerging role of platelets as a key mediator of ALI has been shown in TRALI, sepsis, and T/HS models, and continues to gain clinical support.…”