Effect of nonuniform muscle contraction on sustainability and frequency of triggered arrhythmias in rat cardiac muscle

Masahito Miura, Taichi Nishio, Taiki Hattori, Naomi Murai, Bruno D. Stuyvers, Chiyohiko Shindoh, Penelope A. Boyden

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


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 ([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 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 isoproterenol, 2.5 mmol/L [Ca2+]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 μmol/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 μmol/L SCH00013, a Ca2+ 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 Ca2+ dissociated from myofilaments in cardiac muscle.

Original languageEnglish
Pages (from-to)2711-2717
Number of pages7
Issue number25
Publication statusPublished - 2010 Jun 29


  • arrhythmia
  • calcium
  • myocardial contraction
  • myocardium


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