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• W2034128776 abstract "Myocardial infarction (MI) is a major risk for ventricular arrhythmia. Pause-triggered ventricular arrhythmia can be caused by increased myofilament Ca binding due to sarcomeric mutations or Ca-sensitizing compounds. Myofilament Ca sensitivity is also increased after MI. Here we hypothesize that MI increases risk for pause-triggered ventricular arrhythmias, which can be prevented by myofilament Ca-desensitization and contractile uncoupling. To test this hypothesis, we generated a murine chronic MI model using male B6SJLF1/J mice (n = 40) that underwent permanent ligation of the left anterior descending coronary artery. 4 weeks post MI, cardiac structure, function and myofilament Ca sensitivity were evaluated. Pause-dependent arrhythmia susceptibility was quantified in isolated hearts with pacing trains of increasing frequency, followed by a pause and an extra stimulus. Coronary ligation resulted in a mean infarct size of 39.6 ± 5.7% LV and fractional shortening on echocardiography was reduced by 40% compared to non-infarcted controls. Myofilament Ca sensitivity was significantly increased in post MI hearts (pCa50: Control = 5.66 ± 0.03; MI = 5.84 ± 0.05; P < 0.01). Exposure to the Ca desensitizer/contractile uncoupler blebbistatin (BLEB, 3 μM) reduced myofilament Ca sensitivity of MI hearts to that of control hearts and selectively reduced the frequency of post-pause ectopic beats (MI 0.12 ± 0.04 vs MI + BLEB 0.01 ± 0.005 PVC/pause; P = 0.02). BLEB also reduced the incidence of ventricular tachycardia in chronic MI hearts from 59% to 10% (P < 0.05). We conclude that chronic MI hearts exhibit increased myofilament Ca sensitivity and pause-triggered ventricular arrhythmias, which can be prevented by blebbistatin. Decreasing myofilament Ca sensitivity may be a strategy to reduce arrhythmia burden after MI." @default.
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• W2034128776 date "2013-07-01" @default.
• W2034128776 modified "2023-10-06" @default.
• W2034128776 title "Myofilament calcium de-sensitization and contractile uncoupling prevent pause-triggered ventricular tachycardia in mouse hearts with chronic myocardial infarction" @default.
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• W2034128776 doi "https://doi.org/10.1016/j.yjmcc.2013.03.022" @default.
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