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European Heart Journal Advance Access published online on January 24, 2006

European Heart Journal, doi:10.1093/eurheartj/ehi751
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European Heart Journal © The European Society of Cardiology 2006; all rights reserved
Received October 28, 2005
Revised December 21, 2005
Accepted January 5, 2006

Preclinical research

Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization

Marcella Canton 1, Andreas Skyschally 2, Roberta Menabò 1, Kerstin Boengler 2, Petra Gres 2, Rainer Schulz 2, Michael Haude 3, Raimund Erbel 3, Fabio Di Lisa 1, and Gerd Heusch 2 *

1 Department of Biochemistry, University of Padova, Italy
2 Institute of Pathophysiology, University School of Medicine Essen, Hufelandstr. 55, 45122 Essen, Germany
3 Department of Cardiology, University School of Medicine Essen, Essen, Germany

* To whom correspondence should be addressed.
Gerd Heusch, E-mail: gerd.heusch{at}uni-essen.de


   Abstract

Aims We addressed a potential mechanism of myocardial dysfunction following coronary microembolization at the level of myofibrillar proteins.

Methods and 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).

Conclusion Myofibrillar protein oxidation may represent a mechanistic link between inflammation and contractile dysfunction following coronary microembolization.

Keywords: Microcirculation; Inflammation; Myocardial contraction.
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