ライフサイエンスコーパス: alternan

1 plasmic reticulum Ca(2+) release (ie, Ca(2+) alternans).

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

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

4 nd APDs, which complicates the prediction of alternans.

5 ting eigenmode represents an ideal marker of alternans.

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

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

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

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

10 lternations in AP morphology observed during alternans.

11 n atria AP alternans occurs secondary to CaT alternans.

12 voltage-Ca dynamical systems with respect to alternans.

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

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

15 idation of SERCA2a is a mechanism of cardiac alternans.

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

17 XO is a significant cause of repolarization alternans.

18 ributions of voltage and calcium dynamics to alternans.

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

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

21 s to determine which cellular changes led to alternans.

22 id not significantly change the magnitude of alternans.

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

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

25 ndex of individual propensity to AF than APD alternans.

26 agonist to the development of concordant APD alternans.

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

28 A2a, and increased susceptibility to cardiac alternans.

29 cells contributed to synchronization of this alternans.

30 l role in the molecular mechanism of cardiac alternans.

31 potential duration is a phenomenon known as alternans.

32 an important therapeutic target for cardiac alternans.

33 atrial arrhythmia in association with atrial alternans.

34 ibility to VT/VF secondary to discordant APD alternans.

35 window width-dependent manner, as well as AP alternans.

36 e AP and eliminated both AP duration and CaT alternans.

37 but prolonged APD and failed to suppress CaT alternans.

38 prolonged the AP and failed to eliminate CaT alternans.

39 egy to reduce the risk of arrhythmogenic CaT alternans.

40 fic ion channel inhibitors and activators on alternans.

41 cy threshold and increased the degree of CaT alternans.

42 ose control strategies to inhibit discordant alternans.

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

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

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

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

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 These produced Ca2+ transient alternans and AP alternans, and further caused AP altern

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

54 may also contribute to pathological cardiac alternans and arrhythmia.

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

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

57 To prevent alternans and associated arrhythmias, suitable markers m

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

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

60 nans and AP alternans, and further caused AP alternans and Ca2+ transient alternans through Ca2+->AP

61 the genesis of atrial action potential (AP) alternans and conduction alternans that perpetuate AF.

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

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

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

65 to analyze dynamical mechanisms of transient alternans and EADs.

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

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

68 t CaM-wild type and CaM-M37Q promoted Ca(2+) alternans and prolonged Ca(2+) transient recovery in int

69 ential duration but only IL-6 increased Ca2+ alternans and promoted spontaneous calcium release activ

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

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

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

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

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

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

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

77 ave an effect on the generation of atrial AP alternans and their conduction at the cellular and one-d

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

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

80 Alternans and VF were induced by rapid pacing.

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

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

83 ese produced Ca2+ transient alternans and AP alternans, and further caused AP alternans and Ca2+ tran

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

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

86 indicators, action potential duration, Ca2+ alternans, and spontaneous calcium release (SCR) inciden

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

88 represents a promising strategy to suppress alternans, and thus reducing a risk factor for atrial fi

89 nal 2 degrees atrioventricular block, T-wave alternans, and torsade de pointes (TdP).

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

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

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

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

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

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

96 R2 and how RyR2 inactivation leads to Ca(2+) alternans are unknown.

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

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

99 timulation frequency to 65 bpm and exhibited alternans at >75 bpm.

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

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

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

103 but promoting electromechanically discordant alternans at larger stretch.

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

105 in single atrial myocytes and atrial T-wave alternans at the whole heart level.

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

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 V revealed an involvement of this domain in alternan binding and elongation.

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 ivated Cl(-) channels eliminated AP duration alternans, but prolonged the AP and failed to eliminate

114 ation by 24% (P<0.001, n=15), increased Ca2+ alternans by 300% (P<0.001, n=18), and promoted spontane

115 time the regulation of spatially discordant alternans by STIM1.

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

117 Alternans can be caused by instability of the membrane v

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

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

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

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

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

123 d contributing to a processive elongation of alternan chains.

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

125 wly recorded data for known polysaccharides (alternan, commercial dextran) which also contain alpha-(

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

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

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

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

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

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

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

133 ed a marked increase in the magnitude of APD alternans during rapid pacing, and the emergence of a sp

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

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

136 ASR that could be involved in the control of alternan elongation.

137 1 site, two (Gln(700) and Tyr(717)) promoted alternan elongation.

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

139 The pacing frequency at which CaT alternans emerged was faster, and average CaT alternans

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

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

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

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

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

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

146 Alternans has been linked to ventricular fibrillation, a

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

148 the Neotropical tortoise beetle, Chelymorpha alternans, has been suspected but never systematically e

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

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

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

152 ricular block with 3:1 conduction ratio, QRS alternans in 2:1 atrioventricular block, long-cycle leng

153 vators had no effect on the degree of Ca(2+) alternans in AP voltage-clamped cells, confirming that s

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

155 minate the occurrence of CaT and contraction alternans in atrial tissue.

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

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

158 as subcellular concordant or discordant Ca2+alternans in cardiac myocytes or spatially concordant or

159 ordant or discordant Ca2+ and repolarization alternans in cardiac tissue.

160 S1643 for Kv11.1) abolished both APD and CaT alternans in field-stimulated and current-clamped myocyt

161 lying the increased susceptibility to atrial alternans in HF remains incompletely elucidated.

162 In contrast, nonfailing hMSCs prevented Ca2+ alternans in human cardiac myocytes derived from induced

163 y attenuated or even abolished atrial T-wave alternans in isolated Langendorff perfused hearts.

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

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

166 ed or completely eliminated both CaT and APD alternans in single atrial myocytes and atrial T-wave al

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

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

169 significantly reduce arrhythmogenic cardiac alternans in the failing heart.

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

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

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

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

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

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

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

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

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

179 Alternans is a risk factor for cardiac arrhythmia, inclu

180 Alternans is a well-established risk factor for cardiac

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

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

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

184 At the cellular level alternans is observed as beat-to-beat alternations in co

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

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

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

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

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

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

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

192 Spectral AP alternans magnitude at baseline was highest in persisten

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

194 lternans emerged was faster, and average CaT alternans magnitude was significantly reduced at ZT14 co

195 modelling increased susceptibility to atrial alternans mainly due to the increased sarcoplasmic retic

196 Ca(2+)-CaM is a major determinant of Ca(2+) alternans, making Ca(2+)-CaM dependent regulation of RyR

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

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

199 which is more arrhythmogenic than concordant alternans, may occur in the presence of MEF and when its

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

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

202 be used to suppress spontaneously occurring alternans (n=7), in the presence of myocardial ischemia.

203 Spectral AP alternans near baseline rates can identify patients with

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

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

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

207 2+)-release events and L-type Ca(2+)-current alternans occurred more frequently.

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

209 Furthermore, the amplitude of AP alternans occurring at high pacing frequency was decreas

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

211 new model recapitulates the impact on Ca(2+) alternans of altered CaM and RyR2 functions under 9 diff

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

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

214 Alternans of the cardiac action potential (AP) duration

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

230 and the emergence of a spatially discordant alternans profile in STIM1-KD hearts.

231 Repolarization alternans (RA) are associated with arrhythmogenesis.

232 Repolarization alternans (RA) has been implicated in the pathogenesis o

233 Cardiac alternans refers to a beat-to-beat alternation in contra

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

235 along the nodal line separating out-of-phase alternans regions.

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

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

238 Action potential duration alternans required progressively faster rates for patien

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

240 ity to the formation of spatially discordant alternans, resulting in an increased functional AP propa

241 Increasing evidence suggests that Ca(2+) alternans results from alternations in the inactivation

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

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

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

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

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

247 It was found in both E25 EPS and alternan that NMR parameters could be used to distinguis

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

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

250 ed a novel numerical myocyte model of Ca(2+) alternans that incorporates Ca(2+)-CaM-dependent regulat

251 tion potential (AP) alternans and conduction alternans that perpetuate AF.

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

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

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

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

256 rther caused AP alternans and Ca2+ transient alternans through Ca2+->AP coupling and AP->Ca2+ couplin

257 heterogeneity and converting discordant APD alternans to concordant ones.

258 hat the transition from spatially concordant alternans to spatially discordant alternans, which is mo

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

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

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

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

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

264 ored CL range includes values leading to APD alternans under constant pacing.

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

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

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

268 onstrate that to induce a 1 uV change in the alternans voltage on the body surface, coronary sinus an

269 y surface and intracardiac leads, both Delta(alternans voltage) and DeltaK(score) between baseline an

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

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

272 cells, confirming that suppression of Ca(2+) alternans was caused by the changes in AP morphology.

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

274 1st, 3rd quartiles], 500 ms [500, 500]), APD alternans was detected in only 7 of 27 AF patients (no c

275 and APD heterogeneity, the magnitude of APD alternans was greater (by 80%, P<0.05) in VT/VF(+) versu

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

277 Alternans was measured by APD and spectral analysis.

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

279 type 2 (LQT2) and LQTS type 3 (LQT3), T-wave alternans was observed followed by premature ventricular

280 CaT alternans was observed with and without alternation in t

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

282 Alternans was originally attributed to instabilities in

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

284 e synthesis of both high- and low-molar-mass alternans, we searched for structural traits in ASR that

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

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

287 Pacing-induced AP and CaT alternans were studied in rabbit atrial myocytes using c

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

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

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

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

292 larization can cause Ca(2+) waves and Ca(2+) alternans, which agrees with previous experimental obser

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

294 we investigate the effects of MEF on cardiac alternans, which is an alternation in the width of the a

295 concordant alternans to spatially discordant alternans, which is more arrhythmogenic than concordant

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

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

298 tential intervention to avert development of alternans with important ramifications for arrhythmia pr

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

300 itution to alanine decreased high-molar-mass alternan yield by a third, without significantly impacti