Activation of extracellular signal-regulated kinase after ischemia-reperfusion is required for cardioprotection of sevoflurane-induced preconditioning

• Published in: Journal of Osaka Dental University Vol. 43; no. 1; pp. 1 - 10
• Main Authors: Okusa, Chika, Miyamae, Masami, Sugioka, Shingo, Kaneda, Kazuhiro, Kotani, Junichiro
• Format: Journal Article
• Language: English
• Published: Osaka Odontological Society 2009
• Subjects: C-Jun NH 2-terminal kinase; Extracellular signal-regulated kinase; Heart; Ischemia-reperfusion injury; Preconditioning; Sevoflurane
• ISSN: 0475-2058; 2189-6488
• DOI: 10.18905/jodu.43.1_1

Brief exposure of volatile anesthetics before prolonged ischemia exerts cardioprotective effects mimicking ischemic preconditioning (Anesthetic preconditioning: APC). We previously reported that in contrast to isoflurane-induced myocardial preconditioning, phosphatidylinositol-3-kinase (PI3K)/Akt signaling, which plays a central role in the reperfusion injury salvage kinase cascade, was not involved in sevoflurane-induced preconditioning. Mitogen-activated protein kinases such as extracellular signal-regulated kinase 1/2 (ERK) and stress-activated protein kinase/c-Jun NH 2-terminal kinase (JNK) have also been implicated in APC. The mitogen-activated protein kinase (MEK)/ERK pathway is another reperfusion salvage kinase pathway in ischemic preconditioning. It remains unclear whether this signaling cascade is involved in sevoflurane-induced preconditioning. Isolated perfused guinea pig hearts were subjected to 30min global ischemia and 120min reperfusion (Control group: CTL). Sevoflurane-induced preconditioning was elicited by administration of sevoflurane for 10min at one minimum alveolar concentration with 10min washout before ischemia (Sevoflurane group: SEVO). Contractile recovery was monitored by left ventricular developed pressure (LVDP) and left ventricular end-diastolic pressure (LVEDP). Infarct size was determined by triphenyltetrazolium chloride stain. Phosphorylation of ERK and JNK were assessed by western blot. After ischemia-reperfusion, SEVO had higher LVDP and lower LVEDP than CTL. Infarct size was significantly reduced in SEVO compared to CTL (42±5% vs 21±6%). Phosphorylation of ERK at 10min after reperfusion was significantly increased compared with CTL. Phosphorylation of JNK was the same for the two groups. The MEK/ERK pathway was more important than PI3/Akt signaling in sevoflurane-induced preconditioning.