Document Detail

Restitution analysis of alternans and its relationship to arrhythmogenicity in hypokalaemic Langendorff-perfused murine hearts.
MedLine Citation:
PMID:  17704939     Owner:  NLM     Status:  MEDLINE    
Alternans and arrhythmogenicity were studied in hypokalaemic (3.0 mM K(+)) Langendorff-perfused murine hearts paced at high rates. Epicardial and endocardial monophasic action potentials were recorded and durations quantified at 90% repolarization. Alternans and arrhythmia occurred in hypokalaemic, but not normokalaemic (5.2 mM K(+)) hearts (P<0.01): this was prevented by treatment with lidocaine (10 microM, P<0.01). Fourier analysis then confirmed transition from monomorphic to polymorphic waveforms for the first time in the murine heart. Alternans and arrhythmia were associated with increases in the slopes of restitution curves, obtained for the first time in the murine heart, while the anti-arrhythmic effect of lidocaine was associated with decreased slopes. Thus, hypokalaemia significantly increased (P<0.05) maximal gradients (from 0.55+/-0.14 to 2.35+/-0.67 in the epicardium and from 0.67+/-0.13 to 1.87 +/-0.28 in the endocardium) and critical diastolic intervals (DIs) at which gradients equalled unity (from -2.14+/-0.52 ms to 50.93+/-14.45 ms in the epicardium and from 8.14+/-1.49 ms to 44.64+/-5 ms in the endocardium). While treatment of normokalaemic hearts with lidocaine had no significant effect (P>0.05) on either maximal gradients (0.78+/-0.27 in the epicardium and 0.83+/-0.45 in the endocardium) or critical DIs (6.06+/-2.10 ms and 7.04+/-3.82 ms in the endocardium), treatment of hypokalaemic hearts with lidocaine reduced (P<0.05) both these parameters (1.05+/-0.30 in the epicardium and 0.89+/-0.36 in the endocardium and 30.38+/-8.88 ms in the epicardium and 31.65+/-4.78 ms in the endocardium, respectively). We thus demonstrate that alternans contributes a dynamic component to arrhythmic substrate during hypokalaemia, that restitution may furnish an underlying mechanism and that these phenomena are abolished by lidocaine, both recapitulating and clarifying clinical findings.
Ian N Sabir; Lucia M Li; Andrew A Grace; Christopher L-H Huang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-18
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  455     ISSN:  0031-6768     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-11-21     Completed Date:  2008-06-12     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  653-66     Citation Subset:  IM    
Physiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
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MeSH Terms
Action Potentials
Anti-Arrhythmia Agents / pharmacology
Arrhythmias, Cardiac / etiology,  physiopathology*,  prevention & control
Cardiac Pacing, Artificial
Disease Models, Animal
Endocardium / physiopathology
Fourier Analysis
Heart Rate* / drug effects
Hypokalemia / complications*,  physiopathology
Lidocaine / pharmacology
Models, Cardiovascular
Pericardium / physiopathology
Reproducibility of Results
Time Factors
Grant Support
//British Heart Foundation; //Medical Research Council; //Wellcome Trust
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 137-58-6/Lidocaine

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