alexa Role of the Na Ca exchanger in arrhythmias in compensated hypertrophy.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Pharmacological Reports

Author(s): Sipido KR, Volders PG, Schoenmakers M, De Groot SH, Verdonck F,

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Abstract Sudden, presumably arrhythmic, death is common in heart failure patients. Although total mortality is highest in end-stage failure, the fraction of sudden death in total mortality is higher in the early stages. In each of these stages various, not necessarily identical, ionic mechanisms may contribute to arrhythmogenesis. Dogs with chronic complete atrioventricular block (6-8 weeks) have an increased risk for arrhythmias and sudden death and have compensated biventricular hypertrophy. In this animal model, Ca(2+) release from the sarcoplasmic reticulum (SR) is not reduced. For low frequencies of stimulation, the SR Ca(2+) content is increased, related to a higher activity of the Na/Ca exchanger. Spontaneous Ca(2+) release induces inward Na/Ca exchange current, which can lead to delayed afterdepolarizations (DADs) triggering a new action potential. Such arrhythmogenic DADs and ectopic beats also can be observed in vivo during monophasic action potential recording. They appear after pacing protocols, and/or administration of ouabain, which result in contractile potentiation, suggestive of a enhanced sarcoplasmic reticulum Ca(2+) content. Other arrhythmogenic mechanisms related to increased dispersion of repolarization also can be identified in vivo. Downregulation of delayed K(+) currents is an important factor in prolongation of action potentials. In conclusion, in this animal model of compensated hypertrophy, Ca(2+) handling is different from end-stage heart failure. It is possible that arrhythmogenic mechanisms related to a higher Ca(2+) load contribute to the high incidence of sudden death in stages of compensated hypertrophy before overt heart failure. However, more than one ionic remodeling process is likely to be present, and different cellular mechanisms of arrhythmias can coexist.
This article was published in Ann N Y Acad Sci and referenced in Journal of Pharmacological Reports

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