title: Effects of 2-Octynyladenosine (YT-146) on Mitochondrial Function in Ischemic/Reperfused Rat Hearts.
abstract: This study investigated the effects of an adenosine receptor agonist, 2-octynyladenosine (YT-146), on mitochondrial function in ischemic and ischemic/reperfused hearts. Isolated rat hearts were perfused in the Langendorff manner with a constant flow rate, and exposed to 30 min of ischemia followed by 60 min of reperfusion. Preischemic treatment with YT-146 significantly improved postischemic recovery of left ventricular developed pressure. The high-energy phosphate content in reperfused hearts treated with YT-146 was also more greatly restored than in untreated hearts. YT-146 treatment attenuated the Na(+) content of a mitochondria-enriched fraction, but not the myocardial Na(+) content, at the end of ischemia. These results suggest that preischemic YT-146 treatment preserves the energy-producing ability of mitochondria during ischemia in the Na(+)-accumulated myocardium. YT-146 also attenuated both the sodium lactate-induced decrease in mitochondrial energy-producing ability and the increase in mitochondrial Na(+) concentration in the myocardial skinned fibers. YT-146 may attenuate Na(+) influx to myocardial mitochondria in ischemic cardiac cells, resulting in both preservation of the ability of mitochondria to produce energy and enhancement of the contractile recovery in reperfused hearts. Our findings suggest that the cardioprotective effects of YT-146 against ischemia/reperfusion injury are at least partially due to the preservation of mitochondrial function in the ischemic myocardium.
authors.affiliation: Drug Research Department, Fukushima Research Laboratories, Toa Eiyo Ltd.
authors.forename: Jun
authors.initials: J
authors.lastname: Sasamori
authors.forename: Yohei
authors.initials: Y
authors.lastname: Abe
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Marunouchi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Manome
authors.forename: Takehiro
authors.initials: T
authors.lastname: Uchibori
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tanonaka
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000255:Adenosine Triphosphate / Q000378:metabolism; D000480:Alkynes / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
chemical_list: D000480:Alkynes; D002317:Cardiovascular Agents; D058906:Purinergic P1 Receptor Agonists; D000255:Adenosine Triphosphate; C070494:YT 146; D012964:Sodium; D000241:Adenosine