Effect of Nonuniform Muscle Contraction on Sustainability and Frequency of Triggered Arrhythmias in Rat Cardiac Muscle

Background— Arrhythmias are benign or lethal, depending on their sustainability and frequency. To determine why lethal arrhythmias are prone to occur in diseased hearts, usually characterized by nonuniform muscle contraction, we investigated the effect of nonuniformity on sustainability and frequency of triggered arrhythmias. Methods and Results— Force, membrane potential, and intracellular Ca2+ concentration ([Ca2+]i) were measured in 51 rat ventricular trabeculae. Nonuniform contraction was produced by exposing a restricted region of muscle to a jet of 20 mmol/L 2,3-butanedione monoxime (BDM) or 20 μmol/L blebbistatin. Sustained arrhythmias (>10 seconds) could be induced by stimulus trains for 7.5 seconds only with the BDM or blebbistatin jet (100 nmol/L isoproterenol, 1.0 mmol/L [Ca2+]o, 24°C). During sustained arrhythmias, Ca2+ surges preceded synchronous increases in [Ca2+]i, whereas the stoppage of the BDM jet made the Ca2+ surges unclear and arrested sustained arrhythmias (n=6). With 200 nmol/L iso...