Genre
- Journal Article
The relationships between key features of the cardiac electrical activity, such as electrical restitution, discordant alternans, wavebreak, and reentry, and the onset of ventricular tachyarrhythmias have been characterized extensively under the condition of constant rapid pacing. However, it is unlikely that this scenario applies directly to the clinical situation, where the induction of ventricular tachycardia (VT) typically is associated with the interruption of normal cardiac rhythm by several premature beats. To address this issue, we have developed a general theory to explain why specific patterns of premature stimuli increase dynamic heterogeneity of repolarization and precipitate conduction block. The theory predicts that conduction block is caused by (1) creation of a spatial gradient in diastolic interval (DI) by waves traveling at slightly different velocities (ie, conduction velocity dispersion) and (2) amplification of the spatial gradient in DI over subsequent action potentials, secondary to a strong dependence of action potential duration on the preceding DI (ie, a steep action potential duration restitution function). Tests of this theory have been conducted in computer models of homogeneous tissue, where increased spatial dispersion of repolarization during premature stimulation can be attributed solely to the development of dynamical heterogeneity, and in a canine model exhibiting spontaneously occurring VT and sudden death. Our results thus far indicate that the probability of inducing ventricular fibrillation (VF) in the animal model is highest for those sequences predicted to cause conduction block in the computer model. An understanding of the mechanisms underlying these observations will help to identify key electrical phenomena in the onset of VT and fibrillation. Drug and electrical therapies can then be improved by targeting these specific phenomena.
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. rfg2@cornell.edu
United States
Churchill Livingstone : New York, NY
Accession Number: 17993329. Language: English. Language Code: eng. Date Revised: 20100916. Date Created: 20071112. Date Completed: 20080107. Update Code: 20111122. Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review. Journal ID: 0153605. Publication Model: Print. Cited Medium: Internet. NLM ISO Abbr: J Electrocardiol PubMed Central ID: PMC2128760. Cites: Biophys J. 2006 Aug 1;91(3):805-15. (PMID: 16679366). Cites: Biophys J. 2006 Aug 1;91(3):793-804. (PMID: 16679367). Cites: Cardiovasc Res. 1999 Apr;42(1):65-79. (PMID: 10434997). Cites: Circulation. 1998 Nov 3;98(18):1921-7. (PMID: 9799214). Cites: Nature. 1998 Mar 5;392(6671):78-82. (PMID: 9510250). Cites: Nature. 1998 Mar 5;392(6671):75-8. (PMID: 9510249). Cites: J Cardiovasc Electrophysiol. 1997 Aug;8(8):872-83. (PMID: 9261713). Cites: J Am Coll Cardiol. 1996 May;27(6):1526-33. (PMID: 8626969). Cites: J Am Coll Cardiol. 1994 Jul;24(1):233-43. (PMID: 8006271). Cites: N Engl J Med. 1991 Mar 21;324(12):781-8. (PMID: 1900101). Cites: Circ Res. 1988 Jun;62(6):1191-209. (PMID: 2454762). Cites: J Appl Physiol. 1968 Aug;25(2):191-6. (PMID: 5666097). Cites: Phys Rev E Stat Nonlin Soft Matter Phys. 2003 Mar;67(3 Pt 1):031904. (PMID: 12689098). Cites: Phys Rev Lett. 2002 Sep 23;89(13):138101. (PMID: 12225067). Cites: J Cardiovasc Electrophysiol. 2002 Mar;13(3):292-5. (PMID: 11942602). Cites: Circ Res. 2002 Feb 22;90(3):289-96. (PMID: 11861417). Cites: J Cardiovasc Electrophysiol. 2001 Feb;12(2):196-206. (PMID: 11232619). Cites: Circ Res. 2000 Sep 29;87(7):E25-36. (PMID: 11009627). Cites: Circulation. 2000 Oct 3;102(14):1664-70. (PMID: 11015345). Cites: J Am Coll Cardiol. 2000 Sep;36(3):939-47. (PMID: 10987623). Cites: Proc Natl Acad Sci U S A. 2000 May 23;97(11):6061-6. (PMID: 10811880). Cites: J Cardiovasc Electrophysiol. 1999 Aug;10(8):1087-9. (PMID: 10466489). Linking ISSN: 00220736. Subset: IM. Date of Electronic Publication: 20071101; ID: 17993329
Language
- English
Subjects
- animals
- Humans
- Computer Simulation
- Models, Cardiovascular*
- Heart Conduction System/*physiopathology
- Dogs
- Action Potentials*
- Arrhythmias, Cardiac/*physiopathology