Abstract
ObjectiveHydroxyl radicals (OH*) are involved in the pathogenesis of reperfusion injury, which is observed in many clinical situations including acute heart failure, stroke and myocardial infarction. Two different sub‐cellular defects are involved in the phenotypical OH*‐injury, deranged calcium handling and alterations of myofilament responsiveness.MethodWe temporarily delineated the impact of these two mechanisms at different time points on OH* injury. In order to elucidate the injury response, we measured the amplitude and kinetics of calibrated intracellular Ca2+ transients and twitch contractions simultaneously using ionophoretically loaded bis fura‐2 and potassium contracture.ResultsAfter the exposure of OH* in rabbit trabeculae injury initially there is a marked increase in resting tension (6.27± 0.71 to 46.4 ± 3.49 mN/mm2) in parallel with an increase in diastolic calcium (136.6 ± 7.65 to 779.4 ± 64.63 nM) (n=8). We observed these parameters until a new steady state level was reached. At this new baseline, diastolic calcium returned to near‐normal levels to pre‐OH* levels whereas diastolic force declines, but not all the way to pre‐OH* levels, indicating a sustained injury. We also observed myofilament sensitivity before and after OH* injury through potassium contracture. Myofilament response was increased at the new baseline after OH* injury as compared to the pre‐OH* state.ConclusionThis indicates the acute injury that occurs after OH* exposure is mainly if not entirely is due to calcium overload in acute phase while sustained myocardial dysfunction is mainly due to the altered/increased myofilament responsiveness.
Published Version
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