ライフサイエンスコーパス: alternans

1 ge-driven alternans) or weak (Ca(2+) -driven alternans).

2 XO is a significant cause of repolarization alternans.

3 ributions of voltage and calcium dynamics to alternans.

4 cordant but not discordant SR Ca(2+) and APD alternans.

5 astolic [Ca(2+)]SR alternans and lead to APD alternans.

6 s to determine which cellular changes led to alternans.

7 id not significantly change the magnitude of alternans.

8 tability, as manifested by the degree of APD alternans.

9 ), increase in alpha leads to suppression of alternans.

10 ndex of individual propensity to AF than APD alternans.

11 agonist to the development of concordant APD alternans.

12 time points within the T-wave with positive alternans.

13 A2a, and increased susceptibility to cardiac alternans.

14 cells contributed to synchronization of this alternans.

15 l role in the molecular mechanism of cardiac alternans.

16 potential duration is a phenomenon known as alternans.

17 diastolic interval, can predict the onset of alternans.

18 age-Ca coupling, increasing ISAC promotes Ca alternans.

19 to determine the presence or absence of Ca2+ alternans.

20 nd APDs, which complicates the prediction of alternans.

21 ract collectively to result in whole-cell Ca alternans.

22 ization abnormality such as microwave T wave alternans.

23 ence, also referred to as Ca transient (CaT) alternans.

24 a phenomenon known as subcellular discordant alternans.

25 tes during tissue-level spatially discordant alternans.

26 +) content and L-type Ca(2+) current in this alternans.

27 ting eigenmode represents an ideal marker of alternans.

28 t reached -0.8 and was followed by sustained alternans.

29 logy are the primary cause of pro-arrhythmic alternans.

30 developed to study the mechanisms of Ca(2+) alternans.

31 nisms work synergistically to promote Ca(2+) alternans.

32 ose control strategies to inhibit discordant alternans.

33 lternations in AP morphology observed during alternans.

34 n atria AP alternans occurs secondary to CaT alternans.

35 voltage-Ca dynamical systems with respect to alternans.

36 ng between voltage-driven and Ca(2+) -driven alternans.

37 ng between voltage-driven and calcium-driven alternans.

38 idation of SERCA2a is a mechanism of cardiac alternans.

39 e a profound effect on the occurrence of CaT alternans.

40 pacing threshold for both SR Ca(2+) and APD alternans (188+/-15 and 173+/-12 ms; P<0.05 versus basel

41 The combination of abnormal HRT and T-wave alternans (5 cohorts: 1516 patients) increased the predi

42 an develop without inducing action potential alternans; (5) Pcell action potential alternans develops

43 or ventricular arrhythmia), microvolt T-wave alternans (a marker of electrophysiological vulnerabilit

44 operties of the myocardium, including T-wave alternans, a measure of heterogeneity of repolarization,

45 Cardiac alternans, a putative trigger event for cardiac reentry,

46 ncrease in Ca(2+) transient amplitude before alternans accompanied by a gain of SR Ca(2+), and (3) im

47 Microvolt T wave alternans added information on resuscitated cardiac arre

48 ernans, but only the failing heart shows QRS alternans (although moderate) at rapid pacing.

49 Lower coupling enhanced Ca(2+) alternans amplitude, but the spatial spread of early (<2

50 g and the occurrence of spatially discordant alternans, an arrhythmia that is widely believed to faci

51 T power increases in combination with T-wave alternans analysis.

52 alternans opens new possibilities for atrial alternans and arrhythmia prevention.

53 may also contribute to pathological cardiac alternans and arrhythmia.

54 sight into SR Ca(2+) handling during cardiac alternans and arrhythmia.

55 alternans is an early precursor of cellular alternans and as such will shed more light onto this mec

56 To prevent alternans and associated arrhythmias, suitable markers m

57 ecreased heart rate thresholds for both V(m) alternans and Ca alternans compared with controls (P<0.0

58 the tissue scale, we discuss how cellular Ca alternans and Ca waves promote both reentrant and focal

59 r pathophysiological conditions, leads to Ca alternans and Ca waves.

60 unctional SR refilling time constant on Ca2+ alternans and conclude that physiologically realistic mo

61 timation of lambdaalt to reveal the onset of alternans and distinguishes between voltage-driven and C

62 The mechanisms of alternans and EADs have been extensively studied under s

63 from one state to another, action potential alternans and EADs may occur during the transition betwe

64 to analyze dynamical mechanisms of transient alternans and EADs.

65 Cardiac action potential alternans and early afterdepolarizations (EADs) are link

66 hat can be amplified by diastolic [Ca(2+)]SR alternans and lead to APD alternans.

67 sponsible for electromechanically discordant alternans and quasiperiodic oscillations at the cellular

68 tocol, quantification of subcellular calcium alternans and restitution slope during cycle-length ramp

69 pes, thereby altering the probability of APD alternans and rotor destabilization.

70 hich elucidated the minimal requirements for alternans and spiral wave break up, namely the kinetics

71 conditions, pertaining to calcium-transient alternans and spontaneous release events.

72 are new insights into the genesis of Ca(2+) alternans and spontaneous second Ca(2+) release in cardi

73 association between the occurrence of Ca(2+) alternans and the model parameters of Ca(2+) handling wa

74 be a more sensitive and robust marker of AP alternans and thus a better clinical index of individual

75 icated in cardiac arrhythmias such as T-wave alternans and various tachycardias.

76 Alternans and VF were induced by rapid pacing.

77 of key arrhythmogenic substrate (ie, cardiac alternans) and triggers (ie, sarcoplasmic reticulum Ca(2

78 iques (e.g., heart rate turbulence or T-wave alternans), and imaging modalities (computed tomography

79 i transients, action potential and [Ca(2+)]i alternans, and bursting behaviors.

80 signalling were the primary event leading to alternans, and ICaCC played a decisive role in shaping t

81 anistically links Ca sparks to whole-cell Ca alternans, and is applicable to Ca alternans in both phy

82 lt) and 1:1 regions just before the onset of alternans, and S(dyn)(RP) slopes were statistically simi

83 al R-R intervals), exercise microvolt T wave alternans, and signal-averaged ECG, and corrected QT-tim

84 e- and calcium-driven instabilities underlie alternans, and that the relative contributions of the tw

85 , causing calcium oscillations, AP amplitude alternans, and TWA that were all abolished by calcium cl

86 ternans, converting discordant to concordant alternans, and ultimately preventing wavebreaks.

87 During alternans AP-clamp large CaTs coincided with both long a

88 Intermittent alternans appeared when lambdaalt reached -0.8 and was f

89 It was proposed that alternans appears when the magnitude of the slope of the

90 disturbance of Ca(2+) signaling, whereas APD alternans are a secondary consequence, mediated by Ca(2+

91 Electromechanical and CaT alternans are highly correlated, however, it has remaine

92 In controls, APD alternans arose only at very fast rates (cycle length <2

93 n whom rapid pacing did not initiate AF, APD alternans arose transiently then extinguished.

94 xperimental results) illuminates subcellular alternans as a striking example of a biological Turing i

95 rnans becomes electromechanically discordant alternans as IKs or ISK increase.

96 cted, HF increased susceptibility to cardiac alternans, as evidenced by decreased heart rate threshol

97 ated Ca(2+(i)) events and the development of alternans, as well as isolated and sustained runs of tri

98 egions of the heart: the area that exhibited alternans at B(onset) (1:1(alt)) and the area that did n

99 reductions in kiCa were required to produce alternans at comparable pacing rates in control atrial c

100 t occur in human AF affect the appearance of alternans at heart rates near rest.

101 he percent of samples exhibiting large-scale alternans at higher pacing rates.

102 but promoting electromechanically discordant alternans at larger stretch.

103 tant "emergent" phenomena including cellular alternans at rates > 250 bpm as observed in rabbit myocy

104 We used confocal Ca imaging to measure CaT alternans at the sarcomeric level within individual myoc

105 may be due to the proarrythmic influence of alternans at these slower rates.

106 equencies, and identified the local onset of alternans, B(onset).

107 single time point analysis, microvolt T wave alternans, baroreceptor reflex sensitivity, and SD of al

108 electromechanically (APD-Ca(2+) ) concordant alternans becomes electromechanically discordant alterna

109 The ABCD (Alternans Before Cardioverter Defibrillator) trial is a

110 Inhibition of Cl(-) currents abolished AP alternans, but failed to affect CaT alternans, indicatin

111 magnitude of spatially discordant SR Ca(2+) alternans, but not APD alternans, the pacing threshold f

112 the normal and failing heart develop T-wave alternans, but only the failing heart shows QRS alternan

113 Ca(2+) current with 200 mum Cd(2+) produces alternans by means of a similar fragmentation of the Ca(

114 -wave alternans (ECG ALT) and Ca2+ transient alternans (Ca2+ALT) were induced by rapid pacing (300-12

115 CaT alternans can also become spatially phase-mismatched wit

116 Alternans can be caused by instability of the membrane v

117 irect experimental evidence that subcellular alternans can be dynamically induced in cardiac myocytes

118 In extended cardiac tissue, electrical alternans can be either spatially concordant (SCA, all c

119 simple pacing algorithm by which subcellular alternans can be induced in isolated cardiac myocytes in

120 nal modeling to demonstrate that subcellular alternans can indeed be dynamically induced during stati

121 s a collective behavior of Ca sparks, and Ca alternans can occur even when SR Ca is held constant.

122 ow that the conditions for the onset of Ca2+ alternans cannot be explained solely by the steepness of

123 function, including subtle fine-scale Ca(2+) alternans, captured by optical mapping.

124 at 30% repolarization level during the small alternans CaT was due to reduced ICaCC.

125 form of APs recorded during large and small alternans CaTs were applied to voltage-clamped cells.

126 e investigated the effects of calcium-driven alternans (CDA) on arrhythmia susceptibility in a biophy

127 wer and lower calcium transient, and earlier alternans characteristic of heart failure EP.

128 te thresholds for both V(m) alternans and Ca alternans compared with controls (P<0.01).

129 Here we show that alternans control pacing changes the effective coupling

130 g with a simple feedback control algorithm ("alternans control").

131 estitution slope during cycle-length ramping alternans control, was designed and validated.

132 ion curve, by reducing the propensity of APD alternans, converting discordant to concordant alternans

133 and thus the ability to predict the onset of alternans could be clinically beneficial.

134 tential duration (APD) alternans (discordant alternans; DA).

135 increased from 10 to 30 mV the magnitude of alternans decreased.

136 da' = APD x theta'), and their corresponding alternans depended non-linearly upon diastolic interval

137 Cardiac alternans, described as periodic beat-to-beat alternatio

138 and short AP waveforms, indicating that CaT alternans develop irrespective of AP dynamics.

139 ecrease in Ca(2+) transient amplitude before alternans developed accompanied by a loss of SR Ca(2+),

140 aced with a clamped voltage waveform, but Ca alternans develops as the pacing speeds up.

141 ential alternans; (5) Pcell action potential alternans develops at a shorter cycle length than Vcell,

142 We conclude that alternans develops if the combination of decreased openi

143 out-of-phase action potential duration (APD) alternans (discordant alternans; DA).

144 At fast rates, APD alternans disorganized to complex oscillations en route

145 examine whether the presence of spectral AP alternans during sinus rhythm may obviate the need to ac

146 ECG T-wave alternans (ECG ALT) and Ca2+ transient alternans (Ca2+AL

147 gth (CL), 2 distinct spatial patterns of CaT alternans emerge.

148 ) alternans occurred in-phase, but SR Ca(2+) alternans emerged first as cycle length was progressivel

149 n with theoretical analysis, we show that Ca alternans emerges as a collective behavior of Ca sparks,

150 ight on the underlying mechanisms of cardiac alternans especially when the relative strength of these

151 ntrations of caffeine (100 microm) abolished alternans for a few pulses but the alternans then redeve

152 nuscript, we investigated the role of HRV on alternans formation in isolated cardiac myocytes using n

153 osed mechanism may contribute to subcellular alternans formation in the intact heart.

154 the periodic pacing protocol, it facilitated alternans formation in the isolated cell, but did not si

155 with conduction velocity (CV) restitution on alternans formation using numerical simulations of a map

156 ase of the pacing protocol without feedback, alternans formation was prevented, even in the presence

157 possible dynamical mechanism for subcellular alternans formation, no direct evidence for this mechani

158 ng of the proposed mechanism for subcellular alternans formation, this work (in concert with previous

159 racteristics as the mechanism of subcellular alternans formation.

160 In other examples, phase-matched alternans gradually become phase-mismatched, via the for

161 Cardiac alternans has been linked to the onset of ventricular fi

162 Alternans has been linked to ventricular fibrillation, a

163 Repolarization alternans has been shown to indicate AF vulnerability, b

164 Two mechanisms of Ca(2+) alternans have been demonstrated in these models: one re

165 However, atrial alternans have been observed at slower pacing rates in A

166 We found that increasing ISAC suppresses alternans if the voltage-Ca coupling is positive or the

167 edicted pacing algorithm induces subcellular alternans in a manner consistent with theoretical predic

168 The primary mechanism underlying alternans in atrial cells, similarly to ventricular cell

169 e-cell Ca alternans, and is applicable to Ca alternans in both physiological and pathophysiological c

170 dye affinity can decrease MI by attenuating alternans in Ca(opt) but not in V(opt).

171 ium waves and the genesis of systolic Ca(2+) alternans in cardiac myocytes lacking transverse tubules

172 nd show that it robustly induces subcellular alternans in isolated guinea pig ventricular myocytes.

173 ultaneously, is associated with the onset of alternans in isolated myocytes.

174 + homeostasis which drives proarrhythmic APD alternans in patients with AF.

175 We investigated mechanisms of cardiac alternans in single rabbit atrial myocytes.

176 V restitution does not change the regions of alternans in the cable.

177 significantly reduce arrhythmogenic cardiac alternans in the failing heart.

178 ion portrait is correlated with the onset of alternans in the heart, where the dynamics include a spa

179 itution portrait correlate with the onset of alternans in the heart.

180 ld lead to aggravation of the stress-induced alternans in the tric-a(-/-) muscle.

181 d to different types of spatially discordant alternans in tissue.

182 Recently, "subcellular alternans", in which the Ca transients of adjacent regio

183 erimental studies have reported "subcellular alternans," in which distinct regions of an individual c

184 When the propensity to alternans increases, lambdaalt decreases from 0 to -1.

185 f intracellular Ca(2+) release abolished APD alternans, indicating that [Ca(2+)]i dynamics have a pro

186 ished AP alternans, but failed to affect CaT alternans, indicating that disturbances in Ca(2+) signal

187 Cardiac alternans is a dangerous rhythm disturbance of the heart

188 d controversial whether the primary cause of alternans is a disturbance of cellular Ca(2+) signaling

189 Intracellular calcium (Ca(2+)) alternans is a dynamical phenomenon in ventricular myocy

190 n myocardial infarction (MI), repolarization alternans is a potent arrhythmia substrate that has been

191 ABSTRACT: Cardiac alternans is a precursor to life-threatening arrhythmias

192 Alternans is a risk factor for cardiac arrhythmia, inclu

193 Microscopic calcium alternans is an early precursor of cellular alternans an

194 discordant alternans, which occurs when the alternans is Ca driven with negative voltage-Ca coupling

195 Specifically, when alternans is Ca(2+) -driven, electromechanically (APD-Ca

196 ntal study, however, showed that subcellular alternans is dynamically induced in the remaining subset

197 (V(m)-->Ca coupling), such that subcellular alternans is predicted to occur by a Turing instability

198 Moreover, T-wave alternans is significantly more pronounced in the failin

199 Alternans is the periodic beat-to-beat short-long altern

200 A common approach for the prediction of alternans is to construct the restitution curve, which i

201 f the voltage-Ca coupling is positive or the alternans is voltage driven.

202 n potential duration (APD) of myocytes, i.e. alternans, is believed to be a direct precursor of ventr

203 eity of repolarization as measured by T-wave alternans, known to be associated with arrhythmogenesis,

204 CaT alternans leads to complex beat-to-beat changes in Ca(2+

205 We hypothesized that mechanical alternans (MA) and T-wave alternans (TWA) are associated

206 Spectral AP alternans magnitude at baseline was highest in persisten

207 restitution gradient better correlated with alternans magnitude than either APD or theta restitution

208 At the cellular level alternans manifests as beat-to-beat alternations in cont

209 As such, alternans may present a useful therapeutic target for th

210 theoretical study suggested that subcellular alternans may result during static pacing from a Turing-

211 regression, the magnitude of systolic pulsus alternans measured during AE had predictive sensitivity

212 Conduction velocity and threshold for alternans monotonically increased with coupling.

213 termine whether noninvasive microvolt T-wave alternans (MTWA) testing could identify patients who ben

214 Spectral AP alternans near baseline rates can identify patients with

215 The cellular mechanisms for APD alternans near resting heart rates require definition.

216 ted as an underlying mechanism of electrical alternans observed in patients who experience AF.

217 In AF patients, APD alternans occurred at rates as slow as 100 to 120 bpm, u

218 R Ca(2+) and action potential duration (APD) alternans occurred in-phase, but SR Ca(2+) alternans eme

219 evention of AF, but the mechanism underlying alternans occurrence in AF patients at heart rates near

220 Here we show that in atria AP alternans occurs secondary to CaT alternans.

221 We report the novel finding that alternans of AP morphology is largely sustained by the a

222 Ca(2+)-regulated ion currents that determine alternans of AP morphology.

223 Alternans of the cardiac action potential (AP) duration

224 Beat-to-beat alternation (alternans) of the cardiac action potential duration is k

225 pecifically, it revealed microscopic calcium alternans on the level of individual coupling sites.

226 xes, and state variables, we determined that alternans onset was Ca2+-driven rather than voltage-driv

227 major role of CaCCs in the development of AP alternans opens new possibilities for atrial alternans a

228 Pacing cycle length thresholds to induce CaT alternans or APD alternans were longer in CKD rats than

229 other states such as period 2 or chaos when alternans or EADs occur in pathological conditions.

230 or CLs is strong (typical for voltage-driven alternans) or weak (Ca(2+) -driven alternans).

231 Nodal lines between regions with APD alternans out of phase from each other were correlated w

232 l-p = 0.02) and incidences of repolarisation alternans (p < 0.001) in all mice.

233 d in increasing incidences of repolarisation alternans (p = 0.02).

234 ify the T-wave phase in artificially induced alternans (P<0.0001).

235 actile function (P<0.01), suppressed cardiac alternans (P<0.01), and reduced ryanodine receptor 2 P(o

236 th that in controls (P=0.05) and also Ca(2+) alternans (P=0.03).

237 CaTs can form spatially phase-mismatched alternans patterns after the first few beats following t

238 Cardiac alternans--periodic beat-to-beat alternations in contrac

239 APD alternans preceded all AF episodes and was absent when A

240 developed to quantify the susceptibility to alternans; previous theoretical studies showed that the

241 the synchronization between cells of Ca(2+) alternans produced by small depolarizing pulses.

242 Repolarization alternans (RA) are associated with arrhythmogenesis.

243 e in alpha leads to appearance of additional alternans region.

244 ignificantly reduces AP alternans, while CaT alternans remains unaffected.

245 Tests such as microwave T wave alternans (repolarization abnormality) and signal-averag

246 Microvolt T-wave alternans represents another promising predictor, suppor

247 Action potential duration alternans required progressively faster rates for patien

248 and 93+/-6 versus 76+/-4 ms for CaT and APD alternans, respectively, P<0.05), suggesting increased v

249 False-negative microvolt T wave alternans results were seen in 8% of patients.

250 ded APs (AP-clamp) during pacing-induced CaT alternans revealed a Ca(2+)-dependent current consisting

251 Atrial APD alternans reveals dynamic substrates for AF, arising mos

252 SR Ca(2+) alternans, with SR Ca(2+) release alternans routinely occurring without changes in diastol

253 Ca) produced action potential duration (APD) alternans seen clinically at slower pacing rates.

254 account for previous reports of subcellular alternans seen in statically paced, intact tissue.

255 In current-clamp experiments, APD and CaT alternans strongly correlated in time and magnitude.

256 ng promotes complex EAD patterns such as EAD alternans that are not observed for solely voltage-drive

257 R refractoriness initiates SR Ca(2+) release alternans that can be amplified by diastolic [Ca(2+)]SR

258 the spatial spread of subtle cellular Ca(2+) alternans that relies on a combination of gap-junctional

259 d an important role in the genesis of Ca(2+) alternans that were more obvious in central than in peri

260 Alternans, the beat-to-beat alternation in the shape of

261 discordant SR Ca(2+) alternans, but not APD alternans, the pacing threshold for discordance, or thre

262 abolished alternans for a few pulses but the alternans then redeveloped once SR Ca(2+) content fell t

263 heterogeneity and converting discordant APD alternans to concordant ones.

264 d to confirm the utility of microvolt T-wave alternans to predict ventricular arrhythmias in patients

265 of cell-level Ca(2+) instabilities, known as alternans, to tissue-level arrhythmias is not well under

266 he electrocardiographic phenomenon of T-wave alternans (TWA) (i.e., a beat-to-beat alternation in the

267 ed that mechanical alternans (MA) and T-wave alternans (TWA) are associated with postdischarge outcom

268 by second central moment analysis and T-wave alternans (TWA) by modified moving average analysis.

269 T-wave alternans (TWA) has been implicated in the pathogenesis

270 sted the predictive values of PRD and T-wave alternans (TWA) in 2,965 patients undergoing clinically

271 his study sought to determine whether T-wave alternans (TWA) induced by anger in a laboratory setting

272 lar sarcoplasmic reticulum; (4) Pcell Ca(2+) alternans, unlike Vcell, can develop without inducing ac

273 how these currents affect voltage and Ca(2+) alternans using a physiologically detailed computational

274 ects of stretch-activated currents (ISAC) on alternans using a physiologically detailed model of the

275 taneous TWA during acute ischemia; 77.6% for alternans voltage (P<0.0001) and 92.5% for K(score) (P<0

276 entions compared with baseline, P<0.0001 for alternans voltage; P<0.0001 for K(score)), to suppress T

277 T-wave alternans was analyzed using time-domain methods.

278 The additional markers detected that alternans was Ca(2+) driven in control experiments and v

279 patients (no controls), whereas spectral AP alternans was detected in 18 of 27 AF patients (no contr

280 1st, 3rd quartiles], 500 ms [500, 500]), APD alternans was detected in only 7 of 27 AF patients (no c

281 Langendorff-perfused rabbit hearts in which alternans was induced by periodic pacing at different fr

282 This distinction could be made even before alternans was manifest (specificity/sensitivity >80% for

283 Alternans was measured by APD and spectral analysis.

284 of 27 AF patients (no controls; P=0.003); AP alternans was more prevalent in persistent than paroxysm

285 CaT alternans was observed with and without alternation in t

286 CaT alternans was observed without alternation in L-type Ca(

287 Alternans was originally attributed to instabilities in

288 n the nodal dynamics of spatially discordant alternans, we provide intuition for this observed behavi

289 teristics of action potential duration (APD) alternans were investigated.

290 th thresholds to induce CaT alternans or APD alternans were longer in CKD rats than normal rats (100+

291 Pacing-induced APD and CaT alternans were studied in single rabbit atrial and ventr

292 ram, fragmented QRS, QRS-T angle, and T-wave alternans) were included.

293 l dynamics associated with calcium-transient alternans, wherein the probabilistic nature of dyad acti

294 ted spatially discordant conduction velocity alternans which resulted in nonuniform propagation disco

295 rmine the susceptibility to, and the type of alternans, which are both important to guide preventive

296 heory for the mechanisms of intracellular Ca alternans, which mechanistically links Ca sparks to whol

297 However, for electromechanically discordant alternans, which occurs when the alternans is Ca driven

298 ession of the CaCCs significantly reduces AP alternans, while CaT alternans remains unaffected.

299 SR Ca(2+), and (3) immediate development of alternans with no change of SR content.

300 played a key role in the onset of SR Ca(2+) alternans, with SR Ca(2+) release alternans routinely oc