Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization.
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.
Canton
Marcella
M
Department of Biochemistry, University of Padova, Italy.
Skyschally
Andreas
A
Menabò
Roberta
R
Boengler
Kerstin
K
Gres
Petra
P
Schulz
Rainer
R
Haude
Michael
M
Erbel
Raimund
R
Di Lisa
Fabio
F
Heusch
Gerd
G
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
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014335:Tropomyosin; D014409:Tumor Necrosis Factor-alpha; D001205:Ascorbic Acid; D004229:Dithiothreitol