Reexcitation mechanisms in epicardial tissue: role of \(I_{\mathrm{to}}\) density heterogeneities and \(I_{\mathrm{Na}}\) inactivation kinetics. (English) Zbl 1402.92234
Summary: Dispersion of action potential repolarization is known to be an important arrhythmogenic factor in cardiopathies such as Brugada syndrome. In this work, we analyze the effect of a variation in sodium current (\(I_{\mathrm{Na}}\)) inactivation and a heterogeneous rise of transient outward current (\(I_{\mathrm{to}}\)) in the probability of reentry in epicardial tissue. We use the Luo-Rudy model of epicardial ventricular action potential to study wave propagation in a one-dimensional fiber. Spatial dispersion in repolarization is introduced by splitting the fiber into zones with different strength of \(I_{\mathrm{to}}\). We then analyze the pro-arrhythmic effect of a variation in the relaxation time and steady-state of the sodium channel fast inactivating gate \(h\). We quantify the probability of reentry measuring the percentage of reexcitations that occurs in 200 beats. We find that, for high stimulation rates, this percentage is negligible, but increases notably for pacing periods above 700ms. Surprisingly, with decreasing \(I_{\mathrm{Na}}\) inactivation time, the percentage of reexcitations does not grow monotonically, but presents vulnerable windows, separated by values of the \(I_{\mathrm{Na}}\) inactivation speed-up where reexcitation does not occur. By increasing the strength of \(L\)-type calcium current \(I_{\mathrm{CaL}}\) above a certain threshold, reexcitation disappears. Finally, we show the formation of reentry in stimulated two-dimensional epicardial tissue with modified \(I_{\mathrm{Na}}\) kinetics and \(I_{\mathrm{to}}\) heterogeneity. Thus, we confirm that while \(I_{\mathrm{to}}\) dispersion is necessary for phase-2 reentry, altered sodium inactivation kinetics influences the probability of reexcitation in a highly nonlinear fashion.
MSC:
| 92C50 | Medical applications (general) |
| 92C45 | Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) |
Keywords:
Brugada syndrome; phase-2 reentry; ventricular fibrillation; arrhythmia; dispersion of refractorinessReferences:
| [1] | Aiba, T.; Shimizu, W.; Hidaka, I.; Uemura, K.; Noda, T.; Zheng, C.; Kamiya, A.; Inagaki, M.; Sugimachi, M.; Sunagawa, K., Cellular basis for trigger and maintenance of ventricular fibrillation in the brugada syndrome model-high-resolution optical mapping study, J. am. coll. cardiol., 47, 2074-2085, (2006) |
| [2] | Antzelevitch, C., Heterogeneity and cardiac arrhythmias: an overview, Heart rhythm, 4, 964-972, (2007) |
| [3] | Antzelevitch, C., Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes, Am. J. physiol. heart circ. physiol., 293, H2024-H2038, (2007) |
| [4] | Antzelevitch, C.; Brugada, P.; Brugada, J.; Brugada, R., The brugada syndrome: from bench to bedside, (2005), UK: Blackwell Futura Oxford |
| [5] | Antzelevitch, C.; Brugada, P.; Borggrefe, M.; Brugada, J.; Brugada, R.; Corrado, D.; Gussak, I.; LeMarec, H.; Nademanee, K.; Perez Riera, AR.; Shimizu, W.; Schulze-Bahr, E.; Tan, H.; Wilde, A., Brugada syndrome: report of the second consensus conference, Heart rhythm, 2, 429-440, (2005) |
| [6] | Antzelevitch, C.; Pollevick, GD.; Cordeiro, JM.; Casis, O.; Sanguinetti, MC.; Aizawa, Y.; Guerchicoff, A.; Pfeiffer, R.; Oliva, A.; Wollnik, B.; Gelber, P.; Bonaros, EP.; Burashnikov, E.; Wu, Y.; Sargent, JD.; Schickel, S.; Oberheiden, R.; Bhatia, A.; Hsu, L-F.; Haïssaguerre, M.; Schimpf, R.; Borggrefe, M.; Wolpert, C., Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death, Circulation, 115, 442-449, (2007) |
| [7] | Brahmajothi, MV.; Campbell, DL.; Rasmusson, RL.; Morales, MJ.; Trimmer, JS.; Nerbonne, JM.; Harold, CS, Distinct transient outward potassium current (I_{to}) phenotypes and distribution of fast-inactivating potassium channel alpha subunits in ferret left ventricular myocytes, J. gen. physiol., 113, 581-600, (1999) |
| [8] | Brugada, P.; Brugada, J., Right bundle block, persistent ST segment elevation and cardiac death: a distinct clinical electrocardiographic syndrome—a multicenter report, J. am. coll. cardiol., 20, 1391-1396, (1992) |
| [9] | Casini, S.; Tan, HL.; Bhuiyan, ZA.; Bezzina, CR.; Barnett, P.; Cerbai, E.; Mugelli, A.; Wilde, AAM.; Veldkamp, MW., Characterization of a novel SCN5A mutation associated with brugada syndrome reveals involvement of DIIIS4-S5 linker in slow inactivation, Cardiovasc. res., 76, 418-429, (2007) |
| [10] | Chen, Q.; Kirsch, GE.; Zhang, D.; Brugada, R.; Brugada, J.; Brugada, P.; Potenza, D.; Moya, A.; Borggrefe, M.; Breithardt, G.; Ortiz-Lopez, R.; Wang, Z.; Antzelevitch, C.; O’Brien, RE.; Schulze-Bahr, E.; Keating, MT.; Towbin, JA.; Wang, Q., Genetic basis and molecular mechanisms for idiopathic ventricular fibrillation, Nature, 392, 293-296, (1998) |
| [11] | Clancy, CE.; Rudy, Y., Na+ channel mutation that causes both brugada and long-QT syndrome phenotypes: a simulation study of mechanism, Circulation, 105, 1208-1213, (2002) |
| [12] | Di Diego, JM.; Antzelevitch, C., High [ca^{2+}]0-induced electrical heterogeneity and extrasystolic activity in isolated canine ventricular epicardium: phase 2 reentry, Circulation, 89, 1839-1850, (1994) |
| [13] | Dumaine, R.; Towbin, JA.; Brugada, P.; Vatta, M.; Nesterenko, DW.; Nesterenko, VV., Ionic mechanisms responsible for the electrocardiographic phenotype of the brugada syndrome are temperature dependent, Circ. res., 85, 803-809, (1999) |
| [14] | Grant, AO.; Carboni, MP.; Neplioueva, V.; Starmer, CF.; Memmi, M.; Napolitano, C.; Priori, S., Long QT syndrome, brugada syndrome, and conduction system disease are linked to a single sodium channel mutation, J. clin. invest., 110, 1201-1209, (2002) |
| [15] | Hopenfeld, B., Mechanism for action potential alternans: the interplay between L-type calcium current and transient outward current, Heart rhythm, 3, 345-352, (2006) |
| [16] | Hund, TJ.; Rudy, Y., Determinants of excitability in cardiac myocytes: mechanistic investigation of memory effect, Biophys. J., 79, 3095-3104, (2000) |
| [17] | Inherited Arrhythmias Database. ⟨http://www.fxm.it/cardmoc/〉;.; Inherited Arrhythmias Database. ⟨http://www.fxm.it/cardmoc/〉;. |
| [18] | Li, GR.; Feng, J.; Yue, L.; Carrier, M., Transmural heterogeneity of action potentials and I_{to}1 in myocytes isolated from the human right ventricle, Am. J. physiol. heart circ. physiol., 275, H369-H377, (1998) |
| [19] | Lukas, A.; Antzelevitch, C., Phase 2 reentry as a mechanism of initiation of circus movement reentry in canine epicardium exposed to simulated ischemia, Cardiovasc. res., 32, 593-603, (1996) |
| [20] | Luo, CH.; Rudy, Y., A dynamic model of the cardiac ventricular action potential. I. simulations of ionic currents and concentration changes, Circ. res., 74, 1071-1096, (1994) |
| [21] | Makita, N.; Shirai, N.; Wang, DW.; Sasaki, K.; George, AL.; Kanno, M.; Kitabatake, A., Cardiac na+ channel dysfunction in brugada syndrome is aggravated by β1-subunit, Circulation, 101, 54-60, (2000) |
| [22] | Márquez, MF.; Salica, G.; Hermosillo, AG.; Pastelin, G.; Gómez-Flores, J.; Nava, S.; Cárdenas, M., Ionic basis of pharmacological therapy in brugada syndrome, J. cardiovasc. electrophysiol., 18, 234-240, (2007) |
| [23] | Maury, P.; Hocini, M.; Haïssaguerre, M., Electrical storms in brugada syndrome: review of pharmacologic and ablative therapeutic options, Indian pacing electrophysiol. J., 5, 25-34, (2005) |
| [24] | Miyoshi, S.; Mitamura, H.; Fujikura, K.; Fukuda, Y.; Tanimoto, K.; Hagiwara, Y.; Makoto, I.; Satoshi, O., A mathematical model of phase 2 reentry: role of L-type ca current, Am. J. physiol. heart circ. physiol., 284, H1285-H1294, (2003) |
| [25] | Miyoshi, S.; Mitamura, H.; Fukuda, Y.; Tanimoto, K.; Hagiwara, Y.; Kanki, H.; Seiji, T.; Mitsushige, M.; Toshihisa, M.; Satoshi, O., Link between SCN5A mutation and the brugada syndrome ECG phenotype, Circ. J., 69, 567-575, (2005) |
| [26] | Morita, H.; Zipes, DP.; Lopshire, J.; Morita, ST.; Wu, J., T wave alternans in an in vitro canine tissue model of brugada syndrome, Am. J. physiol. heart circ. physiol., 291, H421-H428, (2006) |
| [27] | Petitprez, S.; Jespersen, T.; Pruvot, E.; Keller, DI.; Corbaz, C.; Schläpfer, J.; Abriel, H.; Kucera, JP., Analyses of a novel SCN5A mutation (C1850S): conduction vs repolarization disorder hypotheses in the brugada syndrome, Cardiovasc. res., 78, 494-504, (2008) |
| [28] | Shajahan, TK.; Sinha, S.; Pandit, R., Spiral-wave dynamics depend sensitively on inhomogeneities in mathematical models of ventricular tissue, Phys. rev. E, 75, 011929, (2007) |
| [29] | Tanaka, H.; Kinoshita, O.; Uchikawa, S.; Kasai, H.; Nakamura, M.; Izawa, A.; Yokoseki, O.; Kitabayashi, H.; Takahashi, W.; Yazaki, Y.; Watanabe, N.; Imamura, H.; Kubo, K., Successful prevention of recurrent ventricular fibrillation by intravenous isoproterenol in a patient with brugada syndrome, Pace, 24, 1293-1294, (2001) |
| [30] | Wilde, AA.; Antzelevitch, C.; Borggrefe, M.; Brugada, J.; Brugada, R.; Brugada, P.; Corrado, D.; Hauer, RNW.; Kass, RS.; Nademanee, K.; Priori, SG.; Towbin, JA., Proposed diagnostic criteria for the brugada syndrome: consensus report, Circulation, 106, 2514-2519, (2002) |
| [31] | Xie, F.; Qu, Z.; Garfinkel, A.; Weiss, JN., Electrophysiological heterogeneity and stability of reentry in simulated cardiac tissue, Am. J. physiol. heart circ. physiol., 280, H535-H545, (2001) |
| [32] | Zhang, Z-S.; Tranquillo, J.; Neplioueva, V.; Bursac, N.; Grand, AO., Sodium channel kinetic changes that produce brugada syndrome or progressive cardiac conduction system disease, Am. J. physiol. heart circ. physiol., 292, H399-H407, (2007) |
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