کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8475188 | 1550445 | 2013 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Myofilament calcium de-sensitization and contractile uncoupling prevent pause-triggered ventricular tachycardia in mouse hearts with chronic myocardial infarction
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کلمات کلیدی
LVPWsIVSsDADLVPWdLVIDdBlebbistatinEADLVIDsPCLIVSdFHCMyocardial infarction - آنفارکتوس میوکاردearly afterdepolarization - اوایل پس از دپولیزاسیونVentricular tachycardia - تاکی کاردی بطنیHeart rate - ضربان قلبpacing cycle length - طول چرخه پیمایشdelayed afterdepolarization - پس از depolarization به تعویق افتادPVC - پلیوینیل کلراید یا پیویسیpremature ventricular complex - پیچیده بطنی زودرسFamilial hypertrophic cardiomyopathy - کاردیومیوپاتی هیپرتروفیک خانوادگی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 60, July 2013, Pages 8-15
Journal: Journal of Molecular and Cellular Cardiology - Volume 60, July 2013, Pages 8-15
نویسندگان
Raghav Venkataraman, Marcelo Perim Baldo, Hyun Seok Hwang, Tiago Veltri, Jose Renato Pinto, Franz J. Baudenbacher, Björn C. Knollmann,