Spiral waves and reentry dynamics in an in vitro model of the healed infarct border zone.
نویسندگان
چکیده
RATIONALE Reentry underlies most ventricular tachycardias (VTs) seen postmyocardial infarction (MI). Mapping studies reveal that the majority of VTs late post-MI arise from the infarct border zone (IBZ). OBJECTIVE To investigate reentry dynamics and the role of individual ion channels on reentry in in vitro models of the "healed" IBZ. METHODS AND RESULTS We designed in vitro models of the healed IBZ by coculturing skeletal myotubes with neonatal rat ventricular myocytes and performed optical mapping at high temporal and spatial resolution. In culture, neonatal rat ventricular myocytes mature to form striated myocytes and electrically uncoupled skeletal myotubes simulate fibrosis seen in the healed IBZ. High resolution mapping revealed that skeletal myotubes produced localized slowing of conduction velocity (CV), increased dispersion of CV and directional-dependence of activation delay without affecting myocyte excitability. Reentry was easily induced by rapid pacing in cocultures; treatment with lidocaine, a Na(+) channel blocker, significantly decreased reentry rate and CV, increased reentry path length and terminated 30% of reentrant arrhythmias (n=18). In contrast, nitrendipine, an L-type Ca(2+) channel blocker terminated 100% of reentry episodes while increasing reentry cycle length and path length and decreasing reentry CV (n=16). K(+) channel blockers increased reentry action potential duration but infrequently terminated reentry (n=12). CONCLUSIONS Cocultures reproduce several architectural and electrophysiological features of the healed IBZ. Reentry termination by L-type Ca(2+) channel, but not Na(+) channel, blockers suggests a greater Ca(2+)-dependence of propagation. These results may help explain the low efficacy of pure Na(+) channel blockers in preventing and terminating clinical VTs late after MI.
منابع مشابه
Cellular Biology Spiral Waves and Reentry Dynamics in an In Vitro Model of the Healed Infarct Border Zone
متن کامل
High-resolution 3-dimensional reconstruction of the infarct border zone: impact of structural remodeling on electrical activation.
RATIONALE Slow nonuniform electric propagation in the border zone (BZ) of a healed myocardial infarct (MI) can give rise to reentrant arrhythmia. The extent to which this is influenced by structural rather than cellular electric remodeling is unclear. OBJECTIVE To determine whether structural remodeling alone in the infarct BZ could provide a substrate for re-entry by (i) characterizing the 3...
متن کاملCALL FOR PAPERS Computational Analyses in Ion Channelopathies Heterogeneous gap junction remodeling stabilizes reentrant circuits in the epicardial border zone of the healing canine infarct: a computational study
Cabo, Candido, and Penelope A. Boyden. Heterogeneous gap junction remodeling stabilizes reentrant circuits in the epicardial border zone of the healing canine infarct: a computational study. Am J Physiol Heart Circ Physiol 291: H2606–H2616, 2006. First published August 25, 2006; doi:10.1152/ajpheart.00346.2006.—The ventricular tachycardias (VTs) that originate in the 5-day epicardial border zon...
متن کاملDissimilarities in the electrophysiological abnormalities of lateral border and central infarct zone cells after healing of myocardial infarction in cats.
We studied the characteristics of an electrophysiological border zone detected after healing of experimental myocardial infarction in cats. Thirty-two isolated left ventricles were studied in tissue bath 2-7 months after distal left coronary artery ligation. Action potentials were recorded from endocardial ventricular muscle cells in normal, lateral border and central infarct zones. Action pote...
متن کاملDynamic relationship of cycle length to reentrant circuit geometry and to the slow conduction zone during ventricular tachycardia.
BACKGROUND Knowledge of cycle-to-cycle changes in isthmus geometry is of potential importance for radiofrequency catheter ablation to stop reentrant ventricular tachycardia. It was hypothesized that isthmus geometry often undergoes continuous evolution throughout reentry and that cycle-length variability measurements could be used to segment reentry into distinct phases and to predict changes i...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation research
دوره 105 11 شماره
صفحات -
تاریخ انتشار 2009