Regional increase in ROS within stretched region exacerbates arrhythmias in rat trabeculae with nonuniform...

In diseased hearts, impaired muscle within the hearts is passively stretched by contractions of the more viable neighboring muscle during the contraction phase. We investigated whether in the myocardium with nonuniform contraction such passive stretch regionally generates ROS within the stretched region and exacerbates arrhythmias. In trabeculae from rat hearts, force, intracellular Ca²⁺, and membrane potential were measured. To assess regional ROS generation, the slope of the change in the 2',7'-dichlorofluorescein fluorescence (DCF_slope) was calculated at the each pixel position along the long axis of trabeculae using DCF fluorescence images. Ca²⁺ waves and arrhythmias were induced by electrical stimulation. A H₂O₂ (1 mmol/L) jet regionally increased the DCF_slope within the jet-exposed region. A blebbistatin (10 μmol/L) jet caused passive stretch of the muscle within the jet-exposed region during the contraction phase and increased the DCF_slope within the stretched region, the velocity of Ca²⁺ waves, and the number of beats after electrical stimulation (0.2 μmol/L isoproterenol), while 3 μmol/L diphenyleneiodonium (DPI), NADPH oxidase inhibitor, decreased them. A jet of a solution containing 0.2 mmol/L H₂O₂ in addition to 10 µmol/L blebbistatin also increased them. A H₂O₂ jet within the region where Ca²⁺ waves propagated increased their velocity. In the myocardium with nonuniform contraction, passive stretch of the muscle by contractions of the neighboring muscle regionally increases ROS within the stretched region, and the regional ROS exacerbates arrhythmias by activating the propagation of Ca²⁺ waves.