Flow of "injury" current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms.

Janse, Michiel J.; Capelle, F J van; Morsink, H; Kléber, André G.; Wilms‐Schopman, Francien J.G.; Cardinal, René; d’Alnoncourt, C. Naumann; Durrer, D

doi:10.1161/01.res.47.2.151

Cited by 581 publications

(251 citation statements)

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“…It has been postulated that "injury" currents flowing through the ischemic border are related to occurrence of ectopic beats and initiation of reentry (29,36). In our work, we did not detect any focal ectopic activity at the border zone.…”

Section: Discussioncontrasting

confidence: 54%

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Sidorov¹,

Uzelac

Wikswo

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Sidorov VY, Uzelac I, Wikswo JP. Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution. Am J Physiol Heart Circ Physiol 301: H209 -H220, 2011. First published May 2, 2011; doi:10.1152/ajpheart.01141.2010.-The heterogeneities of electrophysiological properties of cardiac tissue are the main factors that control both arrhythmia induction and maintenance. Although the local increase of extracellular potassium ([K ϩ ]o) due to coronary occlusion is a well-established metabolic response to acute ischemia, the role of local [K ϩ ]o heterogeneity in phase 1a arrhythmias has yet to be determined. In this work, we created local [K ϩ ]o heterogeneity and investigated its role in fast pacing response and arrhythmia induction. The left marginal vein of a Langendorff-perfused rabbit heart was cannulated and perfused separately with solutions containing 4, 6, 8, 10, and 12 mM of K ϩ . The fluorescence dye was utilized to map the voltage distribution. We tested stimulation rates, starting from 400 ms down to 120 ms, with steps of 5-50 ms. We found that local [K ϩ ]o heterogeneity causes action potential (AP) alternans, 2:1 conduction block, and wave breaks. The effect of [K ϩ ]o heterogeneity on electrical stability and vulnerability to arrhythmia induction was largest during regional perfusion with 10 mM of K ϩ . We detected three concurrent dynamics: normally propagating activation when excitation waves spread over tissue perfused with normal K ϩ , alternating 2:2 rhythm near the border of [K ϩ ]o heterogeneity, and 2:1 aperiodicity when propagation was within the high [K ϩ ]o area. [K ϩ ]o elevation changed the AP duration (APD) restitution and shifted the restitution curve toward longer diastolic intervals and shorter APD. We conclude that spatial heterogeneity of the APD restitution, created with regional elevation of [K ϩ ]o, can lead to AP instability, 2:1 block, and reentry induction. restitution heterogeneity; regional perfusion; optical mapping THE STATIONARY AND DYNAMIC heterogeneities of electrophysiological properties of cardiac tissue play a key role in the induction and maintenance of cardiac arrhythmias (1,10,16,59). Cardiac tissue heterogeneities increase drastically when acute regional ischemia occurs. The early stage of acute ischemia is characterized by abrupt metabolic and electrophysiological changes in the affected area (11). Among them, the more prominent are increased extracellular potassium ([K ϩ ] o ) (25, 26), decreased creatine phosphate (43, 63), elevated intracellular inorganic phosphate (63), acidosis (27, 46), catecholamine release (39), and partial depolarization of transmembrane potential (V m ) (28,36).Since an early change in V m closely relates to [K ϩ ] o accumulation (34, 60), the K ϩ imbalance is considered to be the major factor affecting excitability and is responsible for slow impulse propagation and induction of reentry (51) Although numerous studies have been devoted to investigation ...

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Section: Discussioncontrasting

confidence: 54%

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Sidorov¹,

Uzelac

Wikswo

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…However, since a reentry pathway has never been mapped in its entirety in the intact heart, this mechanism remains an unproven theory and has not gone unchallenged. In a recent provocative investigation, Janse and his co-workers (38) Downar et al (42) showed that porcine ventricular muscle fibers superfused with "ischemic blood" developed the same abnormal electrophysiologic properties that had been recorded from ischemic cells in the intact heart. In an attempt to identifv the ischemic metabolites which produced these abnormalities, they went on to superfuse other muscle fibers with coronary venous blood from normal regions in which they equalized the concentrations of potassium, lactate, oxygen, and hydrogen ion to that of the blood from the ischemic region.…”

Section: Early Phase Arrhythmiasmentioning

confidence: 98%

Electrophysiology of coronary reperfusion. A mechanism for reperfusion arrhythmias.

Murdock¹,

Loeb²,

Euler³

et al. 1980

Circulation

110

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“…During these arrhythmias propagation of the cardiac impulse occurs in multiple circus movements and reentrant excitation is responsible for maintenance of recurrent electrical activity.2 The electrophysiologic conditions necessary for these disturbances of cardiac rhythm were described at the beginning of this century.3 In early myocardial ischemia circulating excitation occurs around a zone of block that may be purely functional in nature. 2 The dimensions of the circus movements in such a case are determined by the product of conduction velocity and refractory period.4 with elevated [K'],. In this way the contribution of accumulation of [K'], to conduction slowing was assessed.…”

mentioning

confidence: 99%

Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart.

Kléber¹,

Janse²,

Wilms-Schopmann³

et al. 1986

Circulation

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229

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Conduction velocities along longitudinal (vL) and transverse (VT) fiber axes were determined in isolated porcine hearts from subepicardial activation patterns that were produced by local stimulation and measured with a multiterminal electrode. [K+], were lower during ischemia than during perfusion with elevated K'. In hearts perfused at 20 mM [K+]."'slow responses" were produced by addition of epinephrine (2.5 x 10-5M). Resting membrane potentials of slow responses were significantly lower than of depressed action potentials during ischemia. The values vL and vT of slow responses (10 and 5 cm/sec) were much lower than the lowest values during ischemia (20 and 10 cm/sec). This indicates that slow conduction in ischemia is associated with depressed action potentials initiated by a partially inactivated rapid Na+ inward current. The time dependence of nonuniform propagation and the relatively high conduction velocities explain two major characteristics of reentrant tachycardias in acute ischemia: (l) the large diameters of reentrant circuits and (2) the beat-to-beat changes in localization of conduction block. Circulation 73, No. 1, [189][190][191][192][193][194][195][196][197][198] 1986

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Flow of "injury" current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms.

Cited by 581 publications

References 35 publications

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Electrophysiology of coronary reperfusion. A mechanism for reperfusion arrhythmias.

Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart.

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