title: Lazaroid U-74389G for cardioplegia-related ischemia-reperfusion injury: an experimental study.
abstract: The adverse effects of myocardial ischemia and reperfusion during cardiopulmonary bypass (CPB) have been thoroughly described. Lazaroid U-74389G, a 21 aminosteroid, has been shown to attenuate ischemia and reperfusion injury and improve recovery in a variety of experimental models.
  
  
  
  Sixteen male swine were randomly divided in two groups. All animals underwent 45 min of ischemic cardioplegic arrest, with U-74389G addition to the standard cardioplegic solution, whereas controls underwent the same procedure without U-74389G. Creatine kinase-MB isoenzyme (CK-MB) and cardiac troponin T levels were measured immediately before CPB (time point 0), during the ischemic period (time point 1) and 30 (time point 2), 60 (time point 3), and 120 (time point 4) min after reperfusion. Myocardial biopsies were obtained at time points 0 and 4.
  
  
  
  CK-MB levels (in U/L) at time points 0-4 were 205 (186-235) versus 219 (196-269; P = 0.72), 215 (167-248) versus 253 (193-339; P = 0.23), 234 (198-255) versus 338 (249-441; P = 0.02), 244 (217-272) versus 354 (269-496; P = 0.01), and 285 (230-321) versus 439 (432-530; P < 0.01) in lazaroid-treated animals versus controls, respectively. Cardiac troponin T levels (in ng/L) at time points 0-4 were 58 (26-287) versus 237 (26-395; P = 0.72), 129 (61-405) versus 265 (145-525; P = 0.23), 261 (123-467) versus 474 (427-1604; P = 0.04), 417 (204-750) versus 841 (584-1818; P = 0.11), and 643 (353-1259) versus 1600 (1378-2313; P < 0.01), respectively. Necrosis grades at time point 4 were 0.0 (0.0-1.0) versus 1.5 (1.0-2.0; P < 0.01) in lazaroid-treated animals versus controls, respectively.
  
  
  
  The present study, in addition to reconfirming the well-described adverse effects of CPB, demonstrates the efficacy of the newer generation lazaroid U-74389G in alleviating these effects.
authors.affiliation: Cardiovascular and Thoracic Surgery Department, Evangelismos Hospital, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Dedeilias
authors.affiliation: Experimental Research Department, ELPEN Pharma, Pikermi, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.affiliation: 2nd Department of Cardiology, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Haidari, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Angelidis
authors.affiliation: 2nd Department of Cardiology, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Haidari, Greece. Electronic address: ggiann@med.uoa.gr.
authors.forename: Georgios
authors.initials: G
authors.lastname: Giannopoulos
authors.affiliation: 2nd Department of Cardiology, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Haidari, Greece.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Deftereos
authors.affiliation: Pathology Department, Sismanogleio Hospital, Marousi, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Chorti
authors.affiliation: Cardiothoracic Surgery Department, Ioannina University Hospital, Ioannina, Greece.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Apostolakis
authors.affiliation: 2nd Anesthesiology Department, National and Kapodistrian University of Athens Medical School, Attikon University Hospital, Haidari, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Kostopanagiotou
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D011281:Pregnatrienes / Q000627:therapeutic use*; D011897:Random Allocation; D013552:Swine; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D011281:Pregnatrienes; C074965:U 74389F
keywords: Cardiopulmonary bypass; Ischemia; Lazaroid; Open chest; Reperfusion; Swine model; U-74389G