Abnormal cardiac repolarization and impulse initiation in German shepherd dogs with inherited ventricular arrhythmias and sudden death

Sosunov, Eugene A.; Anyukhovsky, Evgeny P.; Shvilkin, Alexei; Hara, Motoki; Steinberg, Susan F.; Danilo, Peter; Rosen, Michael R.; Moı̈se, N. Sydney; Mérot, Jocelyn; Probst, Vincent; Charpentier, Flavien; Legeay, Yves; Marec, Hervé Le

doi:10.1016/s0008-6363(98)00333-2

Cited by 33 publications

(32 citation statements)

References 34 publications

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“…These arrhythmias are attributed to triggering by EADs originating in LV Purkinje fibers. 7,8 The present study suggests a substrate for maintenance of these arrhythmias. In the absence of sympathetic stimulation and at a low heart rate, there is significant dispersion of repolarization in the LV of afflicted animals which may facilitate reentry.…”

Section: Discussionmentioning

confidence: 53%

“…27 The present study strengthens the hypothesis that the mechanisms of pause-dependent and tachycardia-dependent lethal arrhythmias in afflicted German shepherds are different. 8 Pause-dependent arrhythmias are most marked when the animals are lying quietly or are asleep. 9 Ventricular tachycardia in these animals typically is initiated by a premature complex coupled to a sinus complex that follows a long pause.…”

Section: Discussionmentioning

confidence: 99%

“…4 -13 Their initiation has been attributed to early afterdepolarizations (EADs), inducing triggered activity that originates from left ventricular (LV) Purkinje fibers. 7,8 However, the substrate contributing to maintenance of this ventricular tachycardia remains unknown. The pause dependence of the arrhythmias as well as the observations that in afflicted dogs (1) the QT interval is not prolonged, 9,10 (2) LV sympathetic innervation is inhomogeneous, 11 and (3) frequent T-wave notching occurs, 10,12 raise the possibility that inhomogeneity of LV repolarization may constitute part of the arrhythmogenic substrate.…”

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confidence: 99%

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Heterogeneous Ventricular Repolarization Provides a Substrate for Arrhythmias in a German Shepherd Model of Spontaneous Arrhythmic Death

et al. 2003

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Background-German shepherd dogs with inherited arrhythmias and sudden death appear to be a model for catecholamine-dependent ventricular tachycardias in human subjects. We tested the hypothesis that heterogeneity of left ventricular repolarization creates an arrhythmogenic substrate for pause-dependent ventricular tachycardia in these animals. Methods and Results-We used microelectrode techniques to record action potentials (AP) from midmyocardial sections of anteroseptal, anterobasal, and posterobasal left ventricular (LV) wall of unafflicted and afflicted dogs. There were no differences in AP duration to 90% repolarization (APD) among LV regions in unafflicted dogs. In contrast, in afflicted dogs, there was significant heterogeneity, with the longest APD in anterobasal and shortest in anteroseptal regions. Isoproterenol did not affect repolarization in unafflicted dogs, whereas in afflicted dogs, it shortened APD anterobasally and prolonged APD anteroseptally. We studied the repolarizing currents, I Kr and I Ks , in single anteroseptal and anterobasal LV myocytes with the use of a whole-cell voltage clamp. There were no differences in I Kr and I Ks between anteroseptal and anterobasal regions in unafflicted dogs, whereas in afflicted dogs, I Kr was smaller anterobasally (PϽ0.05). Isoproterenol produced a more prominent leftward shift in I Ks voltage-dependent activation in anterobasal regions of afflicted than unafflicted dogs. Conclusions-Spatial heterogeneity in expression and catecholamine responsiveness of I Kr and I Ks results in heterogeneous LV repolarization in afflicted German shepherd dogs, contributing importantly to the arrhythmogenic substrate.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Heterogeneous Ventricular Repolarization Provides a Substrate for Arrhythmias in a German Shepherd Model of Spontaneous Arrhythmic Death

et al. 2003

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“…We chose to simulate the EAD waveform using a sinusoid, since this is a reasonable approximation to the EAD waveforms documented in the literature [3,9,10]. EAD amplitude and duration influenced the number of extrasystoles produced, whereas the influence of EAD period was more subtle because the timing of an extrasystole depended on the upstroke of the EAD, and the recovery or adjacent normal tissue.…”

Section: Influence Of Ead Region Size and Waveform Characteristicsmentioning

confidence: 99%

“…Experimental studies show a wide variety of EAD configurations ranging from a single hump in phase 2 or phase 3 of the action potential to several oscillations of membrane potential [3,9,10]. By using a computational model we were able to tightly control not only the location and size of EAD capable regions, but also the EAD waveform characteristics, neither of which can be easily achieved in an experimental model.…”

Section: Introductionmentioning

confidence: 99%