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

Article

关键词: CONGESTIVE-HEART-FAILURE;    IDIOPATHIC DILATED CARDIOMYOPATHY;    TORSADE-DE-POINTES;    CA2+ WAVES;    DELAYED AFTERDEPOLARIZATIONS;    PROPAGATED CONTRACTIONS;    SARCOPLASMIC-RETICULUM;    2,3-BUTANEDIONE MONOXIME;    VENTRICULAR-TACHYCARDIA;    INTACT TRABECULAE;   

DOI  :  10.1161/CIRCULATIONAHA.109.907717

来源: SCIE

【 摘 要 】

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 Ca(2+) concentration ([Ca(2+)](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 mu mol/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 [Ca(2+)](o), 24 degrees C). During sustained arrhythmias, Ca(2+) surges preceded synchronous increases in [Ca(2+)](i), whereas the stoppage of the BDM jet made the Ca(2+) surges unclear and arrested sustained arrhythmias (n = 6). With 200 nmol/L isoproterenol, 2.5 mmol/L [Ca(2+)](o), and the BDM jet, lengthening or shortening of the muscle during sustained arrhythmias accelerated or decelerated their cycle in both the absence (n = 10) and presence (n = 10) of 100 mu mol/L streptomycin, a stretch-activated channel blocker, respectively. The maximum rate of force relaxation correlated inversely with the change in cycle lengths (n = 14; P < 0.01). Sustained arrhythmias with the BDM jet were significantly accelerated by 30 mu mol/L SCH00013, a Ca(2+) sensitizer of myofilaments (n = 10). Conclusion-These results suggest that nonuniformity of muscle contraction is an important determinant of the sustainability and frequency of triggered arrhythmias caused by the surge of Ca(2+) dissociated from myofilaments in cardiac muscle. (Circulation. 2010; 121: 2711-2717.)

【 授权许可】

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