title: Mechanical Pre-Conditioning With Acute Circulatory Support Before Reperfusion Limits Infarct Size in Acute Myocardial Infarction.
abstract: OBJECTIVE
  This study tested the hypothesis that first reducing myocardial work by unloading the left ventricle (LV) with a novel intracorporeal axial flow catheter while delaying coronary reperfusion activates a myocardial protection program and reduces infarct size.
  
  
  BACKGROUND
  Ischemic heart disease is a major cause of morbidity and mortality worldwide. Primary myocardial reperfusion remains the gold standard for the treatment of an acute myocardial infarction (AMI); however, ischemia-reperfusion injury contributes to residual myocardial damage and subsequent heart failure. Stromal cell-derived factor (SDF)-1α is a chemokine that activates cardioprotective signaling via Akt, extracellular regulated kinase, and glycogen synthase kinase-3β.
  
  
  METHODS
  AMI was induced by occlusion of the left anterior descending artery (LAD) via angioplasty for 90 min in 50-kg male Yorkshire swine (n = 5/group). In the primary reperfusion (1° Reperfusion) group, the LAD was reperfused for 120 min. In the primary unloading (1° Unloading) group, after 90 min of ischemia the axial flow pump was activated and the LAD left occluded for an additional 60 min, followed by 120 min of reperfusion. Myocardial infarct size and kinase activity were quantified.
  
  
  RESULTS
  Compared with 1° Reperfusion, 1° Unloading reduced LV wall stress and increased myocardial levels of SDF-1α, CXCR4, and phosphorylated Akt, extracellular regulated kinase, and glycogen synthase kinase-3β in the infarct zone. 1° Unloading increased antiapoptotic signaling and reduced myocardial infarct size by 43% compared with 1° Reperfusion (73 ± 13% vs. 42 ± 8%; p = 0.005). Myocardial levels of SDF-1 correlated inversely with infarct size (R = 0.89; p < 0.01).
  
  
  CONCLUSIONS
  Compared with the contemporary strategy of primary reperfusion, mechanically conditioning the myocardium using a novel axial flow catheter while delaying coronary reperfusion decreases LV wall stress and activates a myocardial protection program that up-regulates SDF-1α/CXCR4 expression, increases cardioprotective signaling, reduces apoptosis, and limits myocardial damage in AMI.
authors.affiliation: The Molecular Cardiology Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts; Surgical and Interventional Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts; The Cardiovascular Center, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts. Electronic address: Nkapur@tuftsmedicalcenter.org.
authors.forename: Navin K
authors.initials: NK
authors.lastname: Kapur
authors.affiliation: The Molecular Cardiology Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Qiao
authors.affiliation: The Molecular Cardiology Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts; Surgical and Interventional Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts; The Cardiovascular Center, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Vikram
authors.initials: V
authors.lastname: Paruchuri
authors.affiliation: The Molecular Cardiology Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Morine
authors.affiliation: The Cardiovascular Center, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Wajih
authors.initials: W
authors.lastname: Syed
authors.affiliation: The Molecular Cardiology Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Sam
authors.initials: S
authors.lastname: Dow
authors.affiliation: The Molecular Cardiology Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Nimish
authors.initials: N
authors.lastname: Shah
authors.affiliation: The Cardiovascular Center, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Natesa
authors.initials: N
authors.lastname: Pandian
authors.affiliation: The Molecular Cardiology Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts; Surgical and Interventional Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts; The Cardiovascular Center, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Karas
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000295:instrumentation / Q000379:methods / Q000401:mortality; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010770:Phosphotransferases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D013314:Stress, Mechanical; D034421:Sus scrofa
chemical_list: D015415:Biomarkers; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D010770:Phosphotransferases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: myocardial infarction; reperfusion injury; ventricular assist devices