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Mechanisms underlying the antifibrillatory action of hyperkalemia in Guinea pig hearts.
- Source :
-
Biophysical journal [Biophys J] 2010 May 19; Vol. 98 (10), pp. 2091-101. - Publication Year :
- 2010
-
Abstract
- Hyperkalemia increases the organization of ventricular fibrillation (VF) and may also terminate it by mechanisms that remain unclear. We previously showed that the left-to-right heterogeneity of excitation and wave fragmentation present in fibrillating guinea pig hearts is mediated by chamber-specific outward conductance differences in the inward rectifier potassium current (I(K1)). We hypothesized that hyperkalemia-mediated depolarization of the reversal potential of I(K1) (E(K1)) would reduce excitability and thereby reduce VF excitation frequencies and left-to-right heterogeneity. We induced VF in Langendroff-perfused guinea pig hearts and increased the extracellular K(+) concentration ([K(+)](o)) from control (4 mM) to 7 mM (n = 5) or 10 mM (n = 7). Optical mapping enabled spatial characterization of excitation dominant frequencies (DFs) and wavebreaks, and identification of sustained rotors (>4 cycles). During VF, hyperkalemia reduced the maximum DF of the left ventricle (LV) from 31.5 +/- 4.7 Hz (control) to 23.0 +/- 4.7 Hz (7.0 mM) or 19.5 +/- 3.6 Hz (10.0 mM; p < 0.006), the left-to-right DF gradient from 14.7 +/- 3.6 Hz (control) to 4.4 +/- 1.3 Hz (7 mM) and 3.2 +/- 1.4 Hz (10 mM), the number of DF domains, and the incidence of wavebreak in the LV and interventricular regions. During 10 mM [K(+)](o), the rotation period and core area of sustained rotors in the LV increased, and VF often terminated. Two-dimensional computer simulations mimicking experimental VF predicted that clamping E(K1) to normokalemic values during simulated hyperkalemia prevented all of the hyperkalemia-induced VF changes. During hyperkalemia, despite the shortening of the action potential duration, depolarization of E(K1) increased refractoriness, leading to a slowing of VF, which effectively superseded the influence of I(K1) conductance differences on VF organization. This reduced the left-to-right excitation gradients and heterogeneous wavebreak formation. Overall, these results provide, to our knowledge, the first direct mechanistic insight into the organization and/or termination of VF by hyperkalemia.<br /> (Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biological Clocks
Blood Flow Velocity
Cardiac Pacing, Artificial methods
Disease Models, Animal
Electrocardiography methods
Electrophysiology methods
Guinea Pigs
Heart physiopathology
Membrane Potentials physiology
Mice
Mice, Transgenic
Models, Cardiovascular
Myocytes, Cardiac
Potassium Channel Blockers therapeutic use
Potassium Channels, Inwardly Rectifying metabolism
Sodium Channels
Action Potentials physiology
Arrhythmias, Cardiac etiology
Heart Conduction System physiology
Hyperkalemia complications
Potassium blood
Ventricular Fibrillation physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1542-0086
- Volume :
- 98
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Biophysical journal
- Publication Type :
- Academic Journal
- Accession number :
- 20483316
- Full Text :
- https://doi.org/10.1016/j.bpj.2010.02.011