title: Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization.
abstract: OBJECTIVE
  We addressed a potential mechanism of myocardial dysfunction following coronary microembolization at the level of myofibrillar proteins.
  
  
  RESULTS
  Anaesthetized pigs underwent intracoronary infusion of microspheres. After 6 h, the microembolized areas (MEA) had decreased systolic wall thickening to 38 +/- 7% of baseline and a 2.62 +/- 0.40-fold increase in the formation of disulphide cross-bridges (DCB) in tropomyosin relative to that in remote areas. The impairment in contractile function correlated inversely with DCB formation (r = -0.68; P = 0.015) and was associated with increased TNF-alpha content. DCB formation was reflected by increased tropomyosin immunoreactivity and abolished in vitro by dithiothreitol. Ascorbic acid prevented contractile dysfunction as well as increased DCB and TNF-alpha. In anaesthetized dogs, 8 h after intracoronary microspheres infusion, contractile function was reduced to 8+/-10% of baseline and DCB in MEA was 1.48+/-0.12 higher than that in remote areas. In conscious dogs, 6 days after intracoronary microspheres infusion, myocardial function had returned to baseline and DCB was no longer different between remote and MEA. Again contractile function correlated inversely with DCB formation (r = -0.83; P = 0.005).
  
  
  CONCLUSIONS
  Myofibrillar protein oxidation may represent a mechanistic link between inflammation and contractile dysfunction following coronary microembolization.
authors.affiliation: Department of Biochemistry, University of Padova, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Canton
authors.forename: Andreas
authors.initials: A
authors.lastname: Skyschally
authors.forename: Roberta
authors.initials: R
authors.lastname: Menabò
authors.forename: Kerstin
authors.initials: K
authors.lastname: Boengler
authors.forename: Petra
authors.initials: P
authors.lastname: Gres
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Michael
authors.initials: M
authors.lastname: Haude
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Lisa
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004285:Dogs; D004617:Embolism / Q000378:metabolism*; D007150:Immunohistochemistry; D008833:Microcirculation / Q000502:physiology; D008863:Microspheres; D009200:Myocardial Contraction / Q000502:physiology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D014335:Tropomyosin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014335:Tropomyosin; D014409:Tumor Necrosis Factor-alpha; D001205:Ascorbic Acid; D004229:Dithiothreitol