title: Chronic Tempol treatment restores pharmacological preconditioning in the senescent rat heart.
abstract: Cardioprotective effects of anesthetic preconditioning and cyclosporine A (CsA) are lost with aging. To extend our previous work and address a possible mechanism underlying age-related differences, we investigated the role of oxidative stress in the aging heart by treating senescent animals with the oxygen free radical scavenger Tempol. Old male Fischer 344 rats (22-24 mo) were randomly assigned to control or Tempol treatment groups for 2 or 4 wk (T×2wk and T×4wk, respectively). Rats received isoflurane 30 min before ischemia-reperfusion injury or CsA just before reperfusion. Myocardial infarction sizes were significantly reduced by isoflurane or CsA in the aged rats treated with Tempol (T×4wk) compared with old control rats. In other experiments, young (4-6 mo) and old rats underwent either chronic Tempol or vehicle treatment, and the levels of myocardial protein oxidative damage, antioxidant enzymes, mitochondrial Ca(2+) uptake, cyclophilin D protein, and mitochondrial permeability transition pore opening times were measured. T×4wk significantly increased MnSOD enzyme activity, GSH-to-GSSH ratios, MnSOD protein level, mitochondrial Ca(2+) uptake capacity, reduced protein nitrotyrosine levels, and normalized cyclophilin D protein expression in the aged rat heart. T×4wk also significantly prolonged mitochondrial permeability transition pore opening times induced by reactive oxygen species in old cardiomyocytes. Our studies demonstrate that 4 wk of Tempol pretreatment restores anesthetic preconditioning and cardioprotection by CsA in the old rat and that this is associated with decreased oxidative stress and improved mitochondrial function. Our results point to a new protective strategy for the ischemic myocardium in the high-risk older population.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Rebecchi
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Peter S A
authors.initials: PS
authors.lastname: Glass
authors.forename: Peter R
authors.initials: PR
authors.lastname: Brink
authors.forename: Lixin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000493:pharmacokinetics; D002316:Cardiotonic Agents / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002316:Cardiotonic Agents; D003497:Cyclic N-Oxides; D013113:Spin Labels; C002744:3-nitrotyrosine; D014443:Tyrosine; D013482:Superoxide Dismutase; D002118:Calcium; C001803:tempol