title: Protective effect of cardioplegia with poly (ADP-ribose) polymerase-1 inhibitor against myocardial ischemia-reperfusion injury: in vitro study of isolated rat heart model.
abstract: Poly(ADP-ribose) polymerase (PARP)-1 inhibitor has been suggested to attenuate the ischemia-reperfusion injury. We investigated the protective effect of the cardioplegia with a PARP-1 inhibitor, 4-hydoxyquinazoline (4-HQ), against myocardial ischemia-reperfusion injury. Isolated rat hearts were perfused on a Langendorff apparatus and cardioplegically arrested for 90 min by perfusion with St. Thomas' Hospital solution (ST-solution). In the Group ST (n = 8), the hearts were arrested with the ST-solution alone. The Group HQ (n = 8) were treated with the ST-solution containing 4-HQ (10 µM) for cardioplegia. During reperfusion, the Group HQ showed significantly greater functional recovery of +dp/dt(max) (p = 0.005) and lower enzymatic leakage (p < 0.01). NAD(+) levels were also preserved higher in the Group HQ (p < 0.01). Immunohistochemical study revealed lesser extents of oxidative stress and apoptosis, in the Group HQ. Thus, addition of 4-HQ in the cardioplegia may provide a new intervention for myocardial protection against ischemia-reperfusion injury by decreasing NAD(+) consumption and suppressing oxidative stress.
authors.affiliation: Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. yamakazu@kuhp.kyoto-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Seigo
authors.initials: S
authors.lastname: Tanaka
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sakata
authors.forename: Senri
authors.initials: S
authors.lastname: Miwa
authors.forename: Wnimonk
authors.initials: W
authors.lastname: Oriyanhan
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Takaba
authors.forename: Kenji
authors.initials: K
authors.lastname: Minakata
authors.forename: Akira
authors.initials: A
authors.lastname: Marui
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Masashi
authors.initials: M
authors.lastname: Komeda
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ueda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D052999:Quinazolinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D006834:Hydrazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D052999:Quinazolinones; D009243:NAD; C085354:4-hydrazinoquinazoline; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1