title: Increased (99m)Tc-sestamibi washout reflects impaired myocardial contractile and relaxation reserve during dobutamine stress due to mitochondrial dysfunction in dilated cardiomyopathy patients.
abstract: OBJECTIVE
  This study investigated whether the technitium-99m sestamibi (MIBI) washout rate (WR) would predict mitochondrial damage and myocardial dysfunction in patients with dilated cardiomyopathy (DCM).
  
  
  BACKGROUND
  Myocardial mitochondrial damage reduces adenosine triphosphate production, resulting in myocardial dysfunction. Increased myocardial (99m)Tc-MIBI washout is reportedly caused by mitochondrial dysfunction.
  
  
  METHODS
  Twenty DCM patients (New York Heart Association functional class I-III) underwent myocardial (99m)Tc-MIBI scintigraphy and cardiac catheterization. Myocardial MIBI uptake was quantified as an early and delayed heart-to-mediastinum ratio, and WR was calculated. Maximum first derivative of left ventricular (LV) pressure (LV dP/dtmax) (an index of myocardial contractility) and LV pressure half-time (T1/2) (an index of myocardial relaxation) were calculated by the left ventricular pressure curve at baseline and during dobutamine infusion (15 μg/kg/min at maximum). Endomyocardial biopsy specimens were obtained for quantitative mRNA analysis and electron microscopy. The patients were divided into two groups as follows: 1) group A of 10 patients showing a WR ≤ 24.3% (median value) and 2) group B of 10 patients showing a WR >24.3%.
  
  
  RESULTS
  WR was significantly correlated with the percentage changes in LV dP/dtmax (%LV dP/dtmax) (r: -0.59; p = 0.01) and T1/2 (r: -0.57; p = 0.03) from baseline to peak dobutamine stress. The %LV dP/dtmax was significantly greater in group B than in group A. The abundance of mRNAs for mitochondrial electron transport-related enzymes was more significantly reduced in group B than in group A. Electron microscopy revealed significant correlations between WR and the severity of mitochondrial damage (r: 0.88; p = 0.048) and glycogen accumulation (r: 0.90; p = 0.044).
  
  
  CONCLUSIONS
  Increased (99m)Tc-MIBI washout may predict mitochondrial dysfunction and the impairment of myocardial contractile and relaxation reserves during dobutamine stress in DCM patients.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hayashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Ohshima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Isobe
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Unno
authors.forename: Hidehito
authors.initials: H
authors.lastname: Funahashi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shinoda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Okumura
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirashiki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kato
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000201:enzymology / Q000503:physiopathology; D025401:Echocardiography, Stress; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000201:enzymology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D017256:Technetium Tc 99m Sestamibi
chemical_list: D045222:Electron Transport Chain Complex Proteins; D012333:RNA, Messenger; D017256:Technetium Tc 99m Sestamibi