title: Monophosphoryl lipid A provides biphasic cardioprotection against ischaemia-reperfusion injury in rat hearts.
abstract: 1 We utilized a rat model of myocardial infarction to investigate whether cardioprotection by monophosphoryl lipid A (MLA) is provided in the early and late phases, as well as to determine whether this cardioprotection may be related to the activation of manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger. 2 Pretreatment with MLA (0.5 or 1.0 mg kg-1, i.v.) 24 h prior to 20-min left coronary artery (LCA) occlusion and 48-h reperfusion significantly decreased the incidence of ventricular fibrillation (VF) during ischaemia, as well as infarct size. Pretreatment with lower concentrations of MLA, however, was ineffective. 3 When we examined the time course of MLA (0.5 mg kg-1)-induced cardioprotection, both infarct size and the incidence of VF were significantly reduced in rats pretreated with MLA 0.5 h and 24 h before occlusion. We observed no differences, however, 2 and 72 h after MLA treatment. 4 The activity of Mn-SOD paralleled the cardioprotective effects of MLA. Mn-SOD activity in the myocardium was significantly enhanced in rats pretreated with MLA (0.5 mg kg-1) 0.5 and 24 h before. Mn-SOD activity was not altered, however, in rats pretreated 2 or 72 h before. Lower MLA concentrations were not effective even 24 h after the treatment. 5 We conclude that MLA treatment induced a biphasic pattern of cardioprotection. The pattern of Mn-SOD activity suggests that this enzyme may play a major role in the acquisition of cardioprotection against ischaemia-reperfusion injury.
authors.affiliation: Division of Cardiology, First Department of Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Hoshida
authors.forename: K
authors.initials: K
authors.lastname: Otsu
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
authors.forename: T
authors.initials: T
authors.lastname: Kuzuya
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000473:pathology / Q000517:prevention & control
chemical_list: D008050:Lipid A; D013482:Superoxide Dismutase; C048436:monophosphoryl lipid A