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

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Abstract
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. 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. 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. 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. 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. British Journal of Pharmacology (1999) 128, 412–418; doi:10.1038/sj.bjp.0702809

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