Oxidative modification of tropomyosin and myocardial dysfunction following coronary microembolization

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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-α 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-α. 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.