Mechanism and time course of S-T and T-Q segment changes during acute regional myocardial ischemia in the pig heart determined by extracellular and intracellular recordings.

Kléber, André G.; Janse, Michiel J.; Capelle, F J van; Durrer, D

doi:10.1161/01.res.42.5.603

Cited by 395 publications

(147 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: 53%

“…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 of both metabolic and electrophysiological events accompanying the early stage of ischemia, there is a lack of systematic examination of the particular role of K ϩ heterogeneity in arrhythmogenesis during suddenly increased heart rate, due to the rapidity of electrophysiological changes after coronary artery occlusion and the complexity of the regional changes in metabolic substrate during ischemia. We address these limitations with a study that has the goals of 1) creating well-defined K ϩ heterogeneities by means of regional perfusion (RP) with solution containing different concentrations of K ϩ ; and 2) investigating the role of K ϩ heterogeneities in the response of cardiac tissue to rapid pacing and arrhythmia induction.…”

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confidence: 99%

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confidence: 99%

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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: 53%

mentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…The decrease in duration of the action potential which has been noted by the measurement of transmembrane potentials (Friedman, Steward, Fenoglio & Wit, 1973;Kleber, Janse, Van Capelle & Durrer, 1978) is due mainly to shortening of the plateau phase of repolarization (Janse & Kleber, 1981). The causes of the shortening are still unresolved.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of ischaemia and hyperkalaemia on myocardial repolarization and conduction times in the dog.

Donaldson¹,

Nashat²,

Noble³

et al. 1984

The Journal of Physiology

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SUMMARY1. The role of increased extracellular K+ concentration ([K+]O) in the production of the early electrophysiological changes induced by myocardial ischaemia, was evaluated by recordings of monophasic action potentials and the paced endocardial evoked response.2. Changes in the duration of local repolarization and conduction time were evaluated during ischaemia, K+ infusion and hypoxia. 7. Absolute reduction in repolarization time during K+ infusion was more marked at the apex than at the base in the epicardial recordings.8. The superimposition of hypoxia on hyperkalaemia resulted in marked slowing of repolarization and conduction time.9. Many but not all of the early electrophysiological abnormalities of acute ischaemia in the intact heart can be related to raised [K+]O.

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“…If the source strengths of the "ischemic nodes" are assigned a constant positive value, then the simulated ECGs will show the DC-shifts following ischemia [27]. These shifts commonly remain unobserved when measuring ECG signals due to the ACcoupling to the ECG amplifiers followed by assigning a zero value to the baseline.…”

Section: Discussionmentioning

confidence: 99%

Genesis of the T wave as based on an equivalent surface source model

Oosterom

2001

Journal of Electrocardiology

110

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Abstract-This article shows the use of the equivalent surface source model in its application to the genesis of the surface ECG in which the sources are of the double layer type. This model has previously been shown to yield an accurate description of body surface potentials during the QRS interval. Its application to the genesis of the T wave is now worked out in greater detail.In this source model, the full spatio-temporal character of the cardiac electric generator is expressed by means of an equivalent double layer situated at the boundary of ventricular tissue. The timing of local depolarization and of repolarization of the cells near this boundary is used to simulate the surface ECG. The background of this source model is discussed, as well as its validity. A matrix formulation is presented of the forward problem of computing the resulting body surface potentials.Based on this forward formulation, an inverse computation of the timing of the repolarization process was performed. Simulated T waves, based on this timing, showed a close correspondence with measured body surface potentials.By taking the inversely computed timing of repolarization as representing the true situation, the model can be used to study in which way perturbations in the timing of local repolarization effect the shape of T waves. An analysis based on this model indicates that the amplitude of the T wave is proportional to the dispersion of the repolarization times at the ventricular surface. The model is also shown to be capable of simulating the ECG changes during local ischemia.

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Mechanism and time course of S-T and T-Q segment changes during acute regional myocardial ischemia in the pig heart determined by extracellular and intracellular recordings.

Cited by 395 publications

References 37 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

Differential effects of ischaemia and hyperkalaemia on myocardial repolarization and conduction times in the dog.

Genesis of the T wave as based on an equivalent surface source model

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