title: Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction.
abstract: Mounting evidence suggests that carbon monoxide (CO) exerts powerful cytoprotective actions. CO-releasing molecules (CORMs) offer an effective means of delivering CO to tissues in vivo. The goal of the present study was to determine whether a water-soluble CORM, tricarbonylchloro(glycinato)ruthenium(II) (CORM-3), induces delayed protection against myocardial infarction 24 h later and to explore the duration of this protection. Mice received a 60-min i.v. infusion of CORM-3 or inactive CORM-3 (which does not release CO) and then, 24, 72, or 120 h later, underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Pretreatment with CORM-3 24 h prior to coronary occlusion markedly reduced infarct size (24.8% +/- 2.9% of the risk region vs. 43.8% +/- 4.4% with inactive CORM-3). The infarct-sparing effect of CORM-3 was still evident 72 h after administration of the CO donor (20.4% +/- 3.7% of the risk region vs. 41.9% +/- 2.5% with inactive CORM-3) but was no longer apparent at 120 h. Both at 24 and 72 h, the protective effects of CORM-3 were equivalent to those afforded by the late phase of ischemic preconditioning (PC; 27.0% +/- 2.9% and 30.3% +/- 3.9% of the risk region, respectively). We conclude that the novel CO-releasing compound, CORM-3, induces delayed protection against myocardial infarction which is similar to that afforded by the late phase of ischemic PC, and that this salubrious effect is sustained for 72 h. To our knowledge, this is the first report that exposure to CO causes the heart to shift to a preconditioned phenotype. In addition, this study provides the first evidence that the cardioprotective actions of ischemic PC persist for 72 h in the mouse.
authors.affiliation: Division of Cardiology, The Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Stein
authors.forename: Yiru
authors.initials: Y
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.forename: Wen-Jian
authors.initials: WJ
authors.lastname: Wu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhu
authors.forename: Qianhong
authors.initials: Q
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Buddhadeb
authors.initials: B
authors.lastname: Dawn
authors.forename: Tony R
authors.initials: TR
authors.lastname: Johnson
authors.forename: Roberto
authors.initials: R
authors.lastname: Motterlini
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight; D002248:Carbon Monoxide / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D009942:Organometallic Compounds / Q000494:pharmacology*; D012307:Risk Factors
chemical_list: D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); D002248:Carbon Monoxide