title: Short-term caloric restriction improves ischemic tolerance independent of opening of ATP-sensitive K+ channels in both young and aged hearts.
abstract: Ischemic tolerance decreases with aging and the cardioprotective effect of ischemic preconditioning (IPC) is impaired in aged animals. Although lifelong caloric restriction (CR) profoundly affects the physiological and pathophysiological modifications induced by aging and markedly increases life span in several species, it is unclear whether short-term CR affects ischemic tolerance and IPC in aged hearts. Six-month-old (Y) and 24-month-old (O) Fischer 344 male rats were randomly divided into two groups; AL rats were fed ad libitum, whereas CR rats were fed 90% of the caloric intake of AL for 2 weeks followed by 65% of the caloric intake for 2 weeks. Isolated perfused hearts were subjected to 25 min of ischemia followed by 30 min of reperfusion with or without IPC. The recovery of LV function after reperfusion improved with IPC in ALY but not in ALO. CR improved the recovery of LV function in both CRY and CRO but the cardioprotective effect of IPC was not additive to that of CR. Neither 5-hydroxydecanoate nor glibenclamide abrogated the protective effect of CR in either CRY or CRO. The recovery of myocardial high-energy phosphates after reperfusion was better with CR in both generations. There was no difference in myocardial expression levels of AMP-activated kinase (AMPK) but AMPK-alpha phosphorylated at Thr172 increased with CR in both Y and O. In conclusion, short-term CR improves myocardial ischemic tolerance independent of the opening of KATP channels in both Y and O. CR-induced cardioprotection is associated with an increase in activated AMPK.
authors.affiliation: Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. shimmura@sc.itc.keio.ac.jp
authors.forename: Ken
authors.initials: K
authors.lastname: Shinmura
authors.forename: Kayoko
authors.initials: K
authors.lastname: Tamaki
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
mesh_terms: D055372:AMP-Activated Protein Kinases; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D031204:Caloric Restriction; D003402:Creatine Kinase / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015424:Reperfusion; D013997:Time Factors; D016276:Ventricular Function
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D009097:Multienzyme Complexes; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D003402:Creatine Kinase; D005905:Glyburide