title: Early repair of moderate ischemic mitral regurgitation reverses left ventricular remodeling: a functional and molecular study.
abstract: BACKGROUND
  Mitral regurgitation (MR) doubles postmyocardial infarction (MI) mortality. We have shown that moderate MR augments remodeling in an apical MI model (no intrinsic MR) with independent left ventricle-to-left atrial MR-type flow. We hypothesized that repairing moderate MR 1 month after MI reverses this remodeling.
  
  
  RESULTS
  Anteroapical MIs were created in 18 sheep, and a left ventricle-to-left atrial shunt implanted in 12 (regurgitant fraction, 30%). Six sheep had the shunt closed at 1 month (repair group). Sheep were compared at baseline, and at 1 and 3 months. Sheep in the MI+MR (unrepaired) and repaired groups remodeled during the first month (120% increased left ventricular end-systolic volume [ESV; P<0.01]), but shunt closure reversed remodeling at 3 months, with end-diastolic volume (EDV) and ESV 135% and 128% of baseline versus 220% and 280% without repair (P<0.001). At 3 months, dP/dt and preload-recruitable stroke work were relatively maintained in the repaired and MI-only groups versus nearly 50% decreases without repair. Prohypertrophic gp130 and antiapoptotic pAkt increased followed by exhaustion below baseline without repair, but remained elevated at 3 months with repair or MI only. With repair, matrix metalloproteinase-2 decreased to < or = 50% that without repair in remote and border zones at 3 months, and the matrix metalloproteinase inhibitor TIMP-4 increased dramatically.
  
  
  CONCLUSIONS
  Early repair of moderate MR in the setting of apical MI substantially reverses the otherwise progressive remodeling process, with reduced left ventricular volumes, relatively maintained contractility, persistently activated intracellular signals promoting hypertrophy and opposing apoptosis, and reduced matrix proteolytic activity. These findings are of interest for the current controversy regarding potential benefits of repair of MR after MI.
authors.affiliation: Cardiac Ultrasound Laboratory, Cardiovascular Research Center, and Cardiothoracic Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Ronen
authors.initials: R
authors.lastname: Beeri
authors.forename: Chaim
authors.initials: C
authors.lastname: Yosefy
authors.forename: J Luis
authors.initials: JL
authors.lastname: Guerrero
authors.forename: Suzan
authors.initials: S
authors.lastname: Abedat
authors.forename: Mark D
authors.initials: MD
authors.lastname: Handschumacher
authors.forename: Robert E
authors.initials: RE
authors.lastname: Stroud
authors.forename: Suzanne
authors.initials: S
authors.lastname: Sullivan
authors.forename: Miguel
authors.initials: M
authors.lastname: Chaput
authors.forename: Dan
authors.initials: D
authors.lastname: Gilon
authors.forename: Gus J
authors.initials: GJ
authors.lastname: Vlahakes
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
mesh_terms: D000818:Animals; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D008297:Male; D008944:Mitral Valve Insufficiency / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D012756:Sheep; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D016326:Extracellular Matrix Proteins