Pharmacologic enhancement of tolerance to ischemic cardiac stress using monophosphoryl lipid A. A comparison with antecedent ischemia.
In comparison with ischemic preconditioning, MLA-mediated cardioprotection seems to show numerous common features. Like ischemia, MLA induces a first and second window (biphasic profile) of heightened tolerance to ischemia. As with delayed ischemic preconditioning, MLA protects against infarction, stunning, and arrhythmias associated with ischemia-reperfusion. In contrast with acute ischemic preconditioning, MLA reduces infarction and stunning. A role has been demonstrated for nitric oxide synthase and KATP channel activation in the mechanism of delayed preconditioning induced by ischemia and by MLA. Regarding acute preconditioning, kinase and KATP channel activation have been implicated as involved in the mechanism of ischemic preconditioning and also in MLA cardioprotection. Use of MLA or related compounds as cardioprotectants may represent a method for inducing acute tolerance to ischemia-reperfusion injury manifested as infarction or stunning, with the added benefit of a sustained delayed cardioprotective state being achieved.
Department of Integrative Pharmacology, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
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D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D004731:Endotoxins / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000503:physiopathology*
D004731:Endotoxins; D008050:Lipid A; C048436:monophosphoryl lipid A