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Myocardial stunning is associated with impaired calcium uptake by sarcoplasmic reticulum
Authors:Sanjay Kumar  Roger J.C. Hall  Kevin P. Moore  Ornella E. Rimoldi  Kenneth T. Macleod
Affiliation:a National Heart & Lung Institute, Imperial College, London, UK
b School of Medicine, Health Policy & Practice, University of East Anglia, Norwich, UK
c Dept. of Medicine, Royal Free Campus, UCL Medical School, University College London, London, UK
d Wales Heart Research Institute, School of Medicine, Cardiff University, Cardiff, UK
Abstract:Myocardial stunning (temporary post-ischaemic contractile dysfunction) may be caused by oxidative stress and/or impaired myocyte calcium homeostasis. Regional myocardial stunning was induced in open-chest pigs (segment shortening reduced to 68.3 ± 4.7% of baseline) by repetitive brief circumflex coronary occlusion (I/R). Reduced glutathione was depleted in stunned myocardium (1.34 ± 0.06 vs. 1.77 ± 0.11 nmol/mg, p = 0.02 vs. remote myocardium) indicating regional oxidant stress, but no regional differences were observed in protein-bound 3-nitrotyrosine or S-nitrosothiol content. Repetitive I/R did not affect myocardial quantities of the sarcolemmal sodium-calcium exchanger, L-type channel, SR calcium ATPase and phospholamban, or the kinetics of ligand binding to L-type channels and SR calcium release channels. However, initial rates of oxalate-supported 45Ca uptake by SR were impaired in stunned myocardium (41.3 ± 13.5 vs. 73.0 ± 15.6 nmol/min/mg protein, p = 0.03). The ability of SR calcium ATPase to sequester cytosolic calcium is impaired in stunned myocardium. This is a potential mechanism underlying contractile dysfunction.
Keywords:Myocardial stunning   Ischaemia   Reperfusion   Calcium   Sarcoplasmic reticulum   Reactive nitrogen species
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