Impact of hydroxyl radical-induced injury on calcium handling and myofilament sensitivity in isolated myocardium

Abstract

Hydroxyl radicals (OH˙) are involved in the pathogenesis of reperfusion injury and are observed in acute heart failure, stroke, and myocardial infarction. Two different subcellular defects are involved in the pathogenesis of OH˙ injury, deranged calcium handling, and alterations of myofilament responsiveness, but their temporal impact on contractile function is not resolved. Initially, after brief OH˙ exposure, there is a corresponding marked increase in diastolic calcium and diastolic force. We followed these parameters until a new steady-state level was reached at ∼45 min post-OH˙ exposure. At this new baseline, diastolic calcium had returned to near-normal, pre-OH˙ levels, whereas diastolic force remained markedly elevated. An increased calcium sensitivity was observed at the new baseline after OH˙-induced injury compared with the pre-OH˙ state. The acute injury that occurs after OH˙ exposure is mainly due to calcium overload, while the later sustained myocardial dysfunction is mainly due to the altered/increased myofilament responsiveness.