title: Role of 12-lipoxygenase in volatile anesthetic-induced delayed preconditioning in mice.
abstract: Delayed cardiac protection mediated by 12-lipoxygenase (12-LO) expression and activity has been linked to opioid receptor stimulation. The role of 12-LO in volatile anesthetic-induced delayed cardiac protection has not been determined. We tested the hypothesis that expression and activity of 12-LO mediate delayed cardiac protection induced by isoflurane in the mouse heart in vivo. Mice were pretreated with 1.4% isoflurane for 30 min and allowed to recover for 1, 12, or 24 h. Immunoblot analysis showed isoflurane significantly enhanced 12-LO protein expression at 12 and 24 h after isoflurane exposure, and this induction of 12-LO was confirmed by immunohistochemistry of whole heart sections at 24 h. The induced protein expression appeared to be localized to intercalated disc regions adjoining adjacent cardiac myocytes. Additionally, mice +/- isoflurane (24 h previously) were subjected to 30 min coronary artery occlusion followed by 2 h of reperfusion in the presence and absence of a 12-LO inhibitor. Isoflurane reduced infarct size (27.1 +/- 2.2% of the area at risk; n = 8) compared with the control group (44.6 +/- 3.6%, n = 8). Baicalein (3 mg/kg), a selective 12-LO inhibitor, blocked the delayed protective effects of isoflurane pretreatment on infarct size (40.6 +/- 3.6%, n = 8). These data suggest that 12-LO is an important mediator of isoflurane-induced delayed preconditioning.
authors.affiliation: Department of Anesthesiology, University of California, San Diego, CA, USA
authors.forename: Yasuo M
authors.initials: YM
authors.lastname: Tsutsumi
authors.forename: Hemal H
authors.initials: HH
authors.lastname: Patel
authors.forename: Diane
authors.initials: D
authors.lastname: Huang
authors.forename: David M
authors.initials: DM
authors.lastname: Roth
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism / Q000502:physiology*; D001784:Blood Gas Analysis; D015153:Blotting, Western; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044950:Flavanones / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane; D016859:Lipoxygenase Inhibitors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure
chemical_list: D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D044950:Flavanones; D016859:Lipoxygenase Inhibitors; C006680:baicalein; D007530:Isoflurane; D001092:Arachidonate 12-Lipoxygenase