Myosin heavy chain and cardiac troponin T damage is associated with impaired myofibrillar ATPase activity contributing to sarcomeric dysfunction in Ca-paradox rat hearts.

This study aimed to explore the potential contribution of myofibrils to contractile dysfunction in Ca-paradox hearts. Isolated rat hearts were perfused with Krebs-Henseleit solution (Control), followed by Ca-depletion, and then Ca-repletion after Ca-depletion (Ca-paradox) by Langendorff method. During heart perfusion left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of pressure development (+ dP/dt), and pressure decay (-dP/dt) were registered.

Heme-induced contractile dysfunction in human cardiomyocytes caused by oxidant damage to thick filament proteins.

Intracellular free heme predisposes to oxidant-mediated tissue damage. We hypothesized that free heme causes alterations in myocardial contractility via disturbed structure and/or regulation of the contractile proteins. Isometric force production and its Ca(2+)-sensitivity (pCa50) were monitored in permeabilized human ventricular cardiomyocytes.

The novel cardiac myosin activator omecamtiv mecarbil increases the calcium sensitivity of force production in isolated cardiomyocytes and skeletal muscle fibres of the rat.

Background And Purpose: Omecamtiv mecarbil (OM) is a novel cardiac myosin activator drug for inotropic support in systolic heart failure. Here we have assessed the concentration-dependent mechanical effects of OM in permeabilized cardiomyocyte-sized preparations and single skeletal muscle fibres of Wistar-Kyoto rats under isometric conditions.

Experimental Approaches: Ca -dependent active force production (F ), its Ca sensitivity (pCa ), the kinetic characteristics of Ca -regulated activation and relaxation, and Ca -independent passive force (F ) were monitored in Triton X-100-skinned preparations with and without OM (3nM-10 μM).

Myeloperoxidase impairs the contractile function in isolated human cardiomyocytes.

We set out to characterize the mechanical effects of myeloperoxidase (MPO) in isolated left-ventricular human cardiomyocytes. Oxidative myofilament protein modifications (sulfhydryl (SH)-group oxidation and carbonylation) induced by the peroxidase and chlorinating activities of MPO were additionally identified. The specificity of the MPO-evoked functional alterations was tested with an MPO inhibitor (MPO-I) and the antioxidant amino acid Met.

Myeloperoxidase evokes substantial vasomotor responses in isolated skeletal muscle arterioles of the rat.

Aims: Myeloperoxidase (MPO) catalyses the formation of a wide variety of oxidants, including hypochlorous acid (HOCl), and contributes to cardiovascular disease progression. We hypothesized that during its action MPO evokes substantial vasomotor responses.

Methods: Following exposure to MPO (1.