Effects of [K+]o on electrical restitution and activation dynamics during ventricular fibrillation

To test whether hyperkalemia suppresses ventricular fibrillation (VF) by reducing the slope of the action potential duration (APD) restitution relation, we determined the effects of the extracellular K+concentration ([K+]o) ([KCl] = 2.7–12 mM) on the restitution of APD and maximum upstroke velocity ( V max) the magnitude of APD alternans and spatiotemporal organization during VF in isolated canine ventricle. As [KCl] was increased incrementally from 2.7 to 12 mM, V max was reduced progressively. Increasing [KCl] from 2.7 to 10 mM decreased the slope of the APD restitution relation at long, but not short, diastolic intervals (DI), decreased the range of DI over which the slope was ≥1, and reduced the maximum amplitude of APD alternans. At [KCl] = 12 mM, the range of DI over which the APD restitution slope was ≥1 increased, and the maximum amplitude of APD alternans increased. For [KCl] = 4–8 mM, the persistence of APD alternans at short DI was associated with maintenance of VF. For [KCl] = 10–12 mM, the spontaneous frequency during VF was reduced, and activation occurred predominantly at longer DI. The lack of APD alternans at longer DI was associated with conversion of VF to a periodic rhythm. These results provide additional evidence for the importance of APD restitution kinetics in the development of VF.

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Cardiac contractility modulation increases action potential duration dispersion and decreases ventricular fibrillation threshold via β1-adrenoceptor activation in the crystalloid perfused normal rabbit heart

International Journal of Cardiology ◽

10.1016/j.ijcard.2013.12.184 ◽

2014 ◽

Vol 172 (1) ◽

pp. 144-154 ◽

Cited By ~ 7

Author(s):

James Winter ◽

Kieran E. Brack ◽

John H. Coote ◽

G. André Ng

Keyword(s):

Ventricular Fibrillation ◽

Action Potential ◽

Action Potential Duration ◽

Cardiac Contractility ◽

Rabbit Heart ◽

Cardiac Contractility Modulation ◽

Ventricular Fibrillation Threshold

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Persistence of the electrophysiologic effects of mexiletine in canine Purkinje fibers alters the response to subsequent hypoxia

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y87-330 ◽

1987 ◽

Vol 65 (10) ◽

pp. 2104-2109

Author(s):

Neil D. Berman ◽

Richard I. Ogilvie ◽

James E. Loukides

Keyword(s):

Action Potential ◽

Action Potential Duration ◽

Free Solution ◽

Purkinje Fibers ◽

Subsequent Exposure ◽

Hydrochloride Solution ◽

Drug Free ◽

Microelectrode Techniques ◽

Upstroke Velocity ◽

Normal Formula

The persistence of cellular electropharmacologic effects of mexiletine on canine Purkinje fibers was studied utilizing standard microelectrode techniques and two different protocols. In the first, the tissue was exposed to hypoxic perfusion before and 30 min after perfusion with one of the following: mexiletine hydrochloride 6.25 μM solution, mexiletine hydrochloride 12.5 μM solution, or drug-free Tyrode's solution. With the higher concentration of mexiletine, depression of the maximal upstroke velocity [Formula: see text] persisted 30 min after drug washout and subsequent exposure to hypoxia did not result in the anticipated shortening of action potential duration but did prevent the restoration of normal [Formula: see text]. After perfusion with the lower concentration of mexiletine, [Formula: see text] was not depressed and hypoxic action potential duration shortening was not prevented. In the second protocol, Purkinje fibers were perfused with 12.5 μM mexiletine hydrochloride solution and then exposed to hypoxia after 15, 30,45, or 60 min of perfusion with drug-free solution. Depression of maximal upstroke velocity and shortening of action potential duration persisted during washout, returning to control values by 45 min, although mexiletine was not detectable in the tissue bath after 10 min of washout. Hypoxia initiated at 15 or 30 min of washout failed to produce the anticipated shortening of action potential duration. At 45 and 60 min, action potential duration was shortened by hypoxia. We concluded that mexiletine depression of [Formula: see text] and shortening of action potential duration may persist in the absence of drug. Further shortening of action potential duration in response to hypoxia is prevented during this period. The persistence of [Formula: see text] depression is prolonged by hypoxia.

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Intramural optical mapping of Vm and Cai2+ during long-duration ventricular fibrillation in canine hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00426.2011 ◽

2012 ◽

Vol 302 (6) ◽

pp. H1294-H1305 ◽

Cited By ~ 9

Author(s):

Wei Kong ◽

Raymond E. Ideker ◽

Vladimir G. Fast

Keyword(s):

Ventricular Fibrillation ◽

Action Potential ◽

Short Duration ◽

Action Potential Duration ◽

Cycle Length ◽

The Other ◽

Membrane Voltage ◽

Long Duration ◽

Intracellular Ca ◽

Rapid Pacing

Intramural gradients of intracellular Ca2+ (Cai2+) Cai2+ handling, Cai2+ oscillations, and Cai2+ transient (CaT) alternans may be important in long-duration ventricular fibrillation (LDVF). However, previous studies of Cai2+ handling have been limited to recordings from the heart surface during short-duration ventricular fibrillation. To examine whether abnormalities of intramural Cai2+ handling contribute to LDVF, we measured membrane voltage ( Vm) and Cai2+ during pacing and LDVF in six perfused canine hearts using five eight-fiber optrodes. Measurements were grouped into epicardial, midwall, and endocardial layers. We found that during pacing at 350-ms cycle length, CaT duration was slightly longer (by ≃10%) in endocardial layers than in epicardial layers, whereas action potential duration (APD) exhibited no difference. Rapid pacing at 150-ms cycle length caused alternans in both APD (APD-ALT) and CaT amplitude (CaA-ALT) without significant transmural differences. For 93% of optrode recordings, CaA-ALT was transmurally concordant, whereas APD-ALT was either concordant (36%) or discordant (54%), suggesting that APD-ALT was not caused by CaA-ALT. During LDVF, Vm and Cai2+ progressively desynchronized when not every action potential was followed by a CaT. Such desynchronization developed faster in the epicardium than in the other layers. In addition, CaT duration strongly increased (by ∼240% at 5 min of LDVF), whereas APD shortened (by ∼17%). CaT rises always followed Vm upstrokes during pacing and LDVF. In conclusion, the fact that Vm upstrokes always preceded CaTs indicates that spontaneous Cai2+ oscillations in the working myocardium were not likely the reason for LDVF maintenance. Strong Vm-Cai2+ desynchronization and the occurrence of long CaTs during LDVF indicate severely impaired Cai2+ handling and may potentially contribute to LDVF maintenance.

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