title: [Na+ overload-induced mitochondrial dysfunction in myocardial ischemia/reperfusion injury].
abstract: An accumulation of Na+ is induced in the ischemic myocardium, which is so-called "Na+ overload". The exact role of Na+ overload in the genesis of myocardial ischemia/reperfusion injury remains unclear except for the role as a driving force of Ca2+ overload in the reperfused myocardium. Excessive activation of Na+/H+ exchanger (NHE) and Na+ channels may contribute to Na+ influx into the ischemic myocardium, resulting in sodium overload under ischemic conditions. A decrease in energy-producing ability of mitochondria in the ischemic myocardium is also observed in an ischemic duration-dependent manner. Attenuation of Na+ overload by an NHE inhibitor or a Na+ channel blocker preserved mitochondrial energy production in the ischemic myocardium and enhanced post-ischemic contractile recovery. To mimic Na+ overload in the ischemic myocardium, isolated mitochondria were incubated with sodium lactate, a possible end product of anaerobic glycolysis. Sodium lactate induced an irreversible reduction in the mitochondrial energy production. The mitochondrial damage induced by sodium lactate was not attenuated by the NHE inhibitor or the Na+ channel blocker, suggesting that these agents may indirectly preserve mitochondrial function in the ischemic myocardium. Taken together, Na+ overload in the ischemic myocardium may induce mitochondrial dysfunction, leading to contractile failure of the reperfused myocardium.
authors.affiliation: Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji 192-0392, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tanonaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takeo
mesh_terms: D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
chemical_list: D012964:Sodium