Septic cardiomyopathy in rat LPS-induced endotoxemia: relative contribution of cellular diastolic Ca 2+ removal pathways, myofibrillar biomechanics properties and action of the cardiotonic drug levosimendan

摘要: Cardiac dysfunction is a common complication in sepsis and characterized by forward pump failure. Hallmarks of septic cardiomyopathy are decreased myofibrillar contractility reduced Ca(2+) sensitivity but it still not clear whether efficiency predominantly diastolic impairment. Moreover, comprehensive picture upstream handling mechanisms downstream myosin biomechanical parameters missing. Ca(2+)-sensitizing agents may be promising mechanistic insights for drugs like levosimendan scarce. Here, we used an endotoxemic LPS rat model to study on vivo hemodynamics, multicellular sensitivity, vitro cellular homeostasis subcellular actomyosin interaction with intracardiac catheters, force transducers, confocal Fluo-4 recordings paced cardiomyocytes, motility assay, respectively. Left ventricular ejection fraction were depressed animals restored levosimendan. Diastolic transient kinetics was slowed down ameliorated Selectively blocking intracellular sarcolemmal extrusion pathways revealed minor contribution sarcoplasmic reticulum ATPase (SERCA) diastole LPS-evoked rather Na(+)/Ca(2+) exchanger plasmalemmal ATPase. This mostly compensated Actin sliding velocities heart extracts from rats. We conclude that endotoxemia specifically impairs resulting overload. Levosimendan, apart stabilizing Ca(2+)-troponin C complexes, potently improves the heart.