Hemmung der p38-MAP-Kinase und der Produktion von Superoxidradikalen erhöht die dehnungs-induzierte myokardiale Kraftentwicklung

TL;DRAbstract

Acute right ventricular (RV) stretch and dilatation predicts RV contractile failure in pulmonary embolism. Myocardial stretch rapidly activates p38 MAP kinase, which decreases calcium sensitivity in isolated cells. We thus tested whether p38 MAP kinase inhibition would preserve contractile function in acutely stretched RV muscle strips. Isolated rabbit RV trabeculae were equilibrated at slack length for 30 rain in Tyrode solution and stimulated at 1HZ, 37°C, 2,5 mM calcium. To determine maximum physiological length (Lmax) and developed force (DF, 100%), trabeculae were stretched gradually over 20 rain until DF during isometric contractions did not increase further. Absolute DF at Lmax was 24,14-3,5 mN/mm 2. Muscles were then adjusted at 88% of Lmax (L88) for 30 min. The p38 MAP kinase inhibitor SB203580 (SB, 101~M) or DMSO (solvent) was added after 5 min at L88. Trabeculae were then acutely restretched at near-maximal (98% of Lmax, L98) or supramaximal (108% of Lmax, L108) length and f

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