Monophosphoryl lipid A provides biphasic cardioprotection against ischaemia-reperfusion injury in rat hearts

We utilized a rat model of myocardial infarction to investigate whether car dioprotection by monophosphoryl lipid A (MLA) is provided in the early and late phases, as well as to determine whether this cardioprotection may be r elated to the activation of manganese superoxide dismutase (Mn-SOD), an int rinsic radical scavenger. 2 Pretreatment with MLA (0.5 or 1.0 mg kg(-1) i.v.) 24 h prior to 20-min le ft coronary artery (LCA) occlusion and 48-h reperfusion significantly decre ased the incidence of ventricular fibrillation (VF) during ischaemia, as we ll as infarct size. Pretreatment with lower concentrations of MLA, however, was ineffective. 3 When we examined the lime course of MLA (0.5 mg kg(-1))-induced cardiopro tection, both infarct size and the incidence of VF were significantly reduc ed 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 pretreat ed with MLA (0.5 mg kg(-1)) 0.5 and 24 h before. Mn-SOD activity was not al tered, however, in rats pretreated 2 or 72 h before. Lower MLA concentratio ns were not effective even 24 h after the treatment. 5 We conclude that MLA treatment induced a biphasic pattern of cardioprotec tion. The pattern of Mn-SOD activity suggests that this enzyme may play a m ajor role in the acquisition of cardioprotection against ischaemia-reperfus ion injury.