title: In vivo MRI and ex vivo histological assessment of the cardioprotection induced by ischemic preconditioning, postconditioning and remote conditioning in a closed-chest porcine model of reperfused acute myocardial infarction: importance of microvasculature.
abstract: Cardioprotective value of ischemic post- (IPostC), remote (RIC) conditioning in acute myocardial infarction (AMI) is unclear in clinical trials. To evaluate cardioprotection, most translational animal studies and clinical trials utilize necrotic tissue referred to the area at risk (AAR) by magnetic resonance imaging (MRI). However, determination of AAR by MRI' may not be accurate, since MRI-indices of microvascular damage, i.e., myocardial edema and microvascular obstruction (MVO), may be affected by cardioprotection independently from myocardial necrosis. Therefore, we assessed the effect of IPostC, RIC conditioning and ischemic preconditioning (IPreC; positive control) on myocardial necrosis, edema and MVO in a clinically relevant, closed-chest pig model of AMI.
  
  
  
  Acute myocardial infarction was induced by a 90-min balloon occlusion of the left anterior descending coronary artery (LAD) in domestic juvenile female pigs. IPostC (6 × 30 s ischemia/reperfusion after 90-min occlusion) and RIC (4 × 5 min hind limb ischemia/reperfusion during 90-min LAD occlusion) did not reduce myocardial necrosis as assessed by late gadolinium enhancement 3 days after reperfusion and by ex vivo triphenyltetrazolium chloride staining 3 h after reperfusion, however, the positive control, IPreC (3 × 5 min ischemia/reperfusion before 90-min LAD occlusion) did. IPostC and RIC attenuated myocardial edema as measured by cardiac T2-weighted MRI 3 days after reperfusion, however, AAR measured by Evans blue staining was not different among groups, which confirms that myocardial edema is not a measure of AAR, IPostC and IPreC but not RIC decreased MVO.
  
  
  
  We conclude that IPostC and RIC interventions may protect the coronary microvasculature even without reducing myocardial necrosis.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Baranyai
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.|Pharmahungary Group, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Giricz
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltán V
authors.initials: ZV
authors.lastname: Varga
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Koncsos
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Dominika
authors.initials: D
authors.lastname: Lukovic
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Makkos
authors.affiliation: Department of Biochemistry, University of Szeged, Szeged, Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Sárközy
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Noémi
authors.initials: N
authors.lastname: Pávó
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
authors.forename: András
authors.initials: A
authors.lastname: Jakab
authors.affiliation: The Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Czimbalmos
authors.affiliation: The Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Vágó
authors.affiliation: The Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Ruzsa
authors.affiliation: Institute of Diagnostic Imaging and Radiation Oncology, University of Kaposvár, Kaposvár, Hungary.|Department of Radiology, University of Pécs, Pecs, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Tóth
authors.affiliation: Institute of Diagnostic Imaging and Radiation Oncology, University of Kaposvár, Kaposvár, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Garamvölgyi
authors.affiliation: The Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
authors.affiliation: Institute of Physiology, Justus Liebig University, Giessen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Mariann
authors.initials: M
authors.lastname: Gyöngyösi
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary. peter.ferdinandy@pharmahungary.com.|Department of Biochemistry, University of Szeged, Szeged, Hungary. peter.ferdinandy@pharmahungary.com.|Pharmahungary Group, Szeged, Hungary. peter.ferdinandy@pharmahungary.com.
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000378:metabolism*; D004487:Edema / Q000473:pathology; D004562:Electrocardiography; D005260:Female; D006334:Heart Function Tests; D006439:Hemodynamics; D057775:Ischemic Postconditioning; D019157:Ischemic Preconditioning, Myocardial; D008279:Magnetic Resonance Imaging / Q000379:methods*; D055806:Microvessels / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D009336:Necrosis; D013194:Staining and Labeling; D034421:Sus scrofa
chemical_list: D002316:Cardiotonic Agents
keywords: Area at risk; Ischemia/reperfusion injury; Ischemic postconditioning; Ischemic preconditioning; Myocardial edema; Remote conditioning