Increased susceptibility to reentrant arrhythmias by flecainide.
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Arrhythmias, Cardiac↗
Biomedical subjects
L Boersma
Publications and source records attributed to L Boersma.
Echo-wave termination of ventricular tachycardia. A common mechanism of termination of reentrant arrhythmias by various pharmacological interventions.
BACKGROUND: Based on epicardial mapping, different mechanisms of termination of reentrant ventricular tachycardia by various pharmacological interventions are described. METHODS AND RESULTS: In 40 Langendorff-perfused rabbit hearts, rings of anisotropic left ventricular epicardium were made by a cryoprocedure. Sustained monomorphic ventricular tachycardia based on continuous circus movement of the impulse around the ring was induced by programmed stimulation. Increasing doses of heptanol (n = 10), potassium (n = 10), tetrodotoxin (n = 6), RP62719 (a new class III drug) (n = 4), flecainide (n = 5), and propafenone (n = 5) were administered to terminate ventricular tachycardia. Epicardial mapping (248 points) was used to study the mechanism of termination of ventricular tachycardia. In 28 of 40 hearts, ventricular tachycardia terminated because the drugs produced complete conduction block of the impulse in a segment of the reentrant pathway. In the remaining 12 hearts (heptanol, n = 2; potassium, n = 3; tetrodotoxin, n = 2; RP62719, n = 2; flecainide, n = 1; and propafenone, n = 2), termination of ventricular tachycardia occurred by collision of the circulating impulse with a spontaneous antidromic wave front reflected within the circuit. This phenomenon occurred when the circulating impulse encountered an arc of functional conduction block that did not extend along the whole width of the ring. As a result, the impulse dissociated into a continuing orthodromic circulating wave and a returning antidromic echo-wave caused by microreentry within the ring. CONCLUSIONS: Independent of their mechanisms of action, sodium channel blockers, electrical uncouplers, and class III drugs terminate reentrant ventricular tachycardia either by complete conduction block or by collision of the impulse with an echo-wave.
Animals↗
Sustained monomorphic ventricular tachycardia: a single electrocardiographic expression of different patterns of reentry.
UNLABELLED: Sustained monomorphic ventricular tachycardia (SMVT) can be the electrocardiographic expression of a reentrant impulse in the ventricles. In this study we analyzed the different types of reentry that might lead to SMVT. METHODS: The pattern of activation of 73 episodes of SMVT induced in thin sheets of epicardium in 50 Langendorff perfused rabbit hearts were visualized with high resolution epicardial mapping (248 points). RESULTS: Five different patterns of reentry resulting in SMVT were identified: (1) Single-loop reentry around a fixed obstacle (n = 40); (2) Single-loop reentry around a functional arc of conduction block (n = 17); (3) Double-wave reentry around a fixed obstacle (n = 9); (4) Figure-of-eight reentry around two areas of functional block (n = 5); and (5) Multiple synchronized circuits around multiple areas of functional block (n = 2). CONCLUSION: SMVT is a single electrocardiographic expression of different patterns of reentry. Accurate mapping is mandatory to identify the reentrant pathway and the pathophysiological substrate of the arrhythmia.
Animals↗
On the mechanisms of ventricular tachycardia acceleration during programmed electrical stimulation.
BACKGROUND: The pathophysiological mechanisms leading to acceleration of ventricular tachycardia (VT) are still unclear. METHODS AND RESULTS: High-resolution epicardial mapping was used to study the mechanisms of VT acceleration by programmed electrical stimulation (PES) in a model of sustained reentrant VT in Langendorff-perfused rabbit hearts (n = 40). Three different mechanisms responsible for acceleration of VT were identified: 1) induction of double-wave reentry (n = 6), defined as the occurrence of two successive activation waves circulating in the same direction in the same circuit; 2) change to a functionally determined circuit (n = 4), defined as reentry of the impulse around a functional line of block without involvement of a fixed obstacle; and 3) change of the reentrant circuit to reentry within a different, faster anatomic pathway (n = 3). Analysis of 81 episodes of sustained monomorphic VT induced by PES in 74 patients with clinically documented sustained VT in the setting of chronic coronary artery disease showed that in 22 episodes VT was suddenly accelerated by PES (mean cycle length, from 345 +/- 73 to 277 +/- 71 msec, p less than 0.01). CONCLUSIONS: With the observations made in the experimental model, the following tentative classification of the mechanisms of VT acceleration of the 22 episodes was made: 1) induction of double-wave reentry in two, 2) change to a functionally determined circuit in four, and 3) change to reentry within a faster anatomic circuit in 16. Simple criteria suggest that these mechanisms may apply in the clinical situation.
Animals↗
Reentrant excitation around a fixed obstacle in uniform anisotropic ventricular myocardium.
BACKGROUND: The purpose of this study was to investigate the role of tissue anisotropy and dispersion of refractoriness on initiation of reentrant ventricular tachycardia (VT). METHODS AND RESULTS: A ring of perfused uniform anisotropic ventricular epicardium in Langendorff-perfused rabbit hearts was created by an endocardial freezing technique. High-resolution mapping (248 channels) was used to analyze epicardial activation of the left ventricle. One to three premature beats were induced at a total of 272 points in 17 experiments (16 different points around the ring in each experiment). Reentrant VT could be initiated at 43 of the 272 points tested. The cycle length of VT was stable and ranged from 128 to 198 msec (mean, 161 +/- 19 msec). Correlation between conduction velocity and the angle between the circulating activation wave and epicardial fiber orientation showed that in segments of the ring where conduction was perpendicular to the fiber axis, mean conduction velocity was 25 +/- 5 cm/sec compared with 60 +/- 7 cm/sec when conduction was parallel to the fiber orientation. Analysis of the site of unidirectional conduction block showed that in 41 of 43 cases, block occurred while the impulse was propagating parallel to the fiber orientation. Measurement of the refractory periods at either side of the line of unidirectional block showed that only in 12 of 43 cases did block occur while the impulse was propagating into an area with a longer (more than 10 msec) refractory period. CONCLUSIONS: In uniform anisotropic ventricular myocardium, reentrant VT is initiated because lowering the stimulating efficacy of the depolarization wave by premature beats leads to preferential conduction block parallel to the fiber orientation.
Animals↗
Differential effects of heptanol, potassium, and tetrodotoxin on reentrant ventricular tachycardia around a fixed obstacle in anisotropic myocardium.
BACKGROUND: The aim of this study was to test the hypothesis that electrical uncoupling and depression of the fast sodium channels have differential effects on propagation of the electrical impulse relative to the fiber orientation. METHODS AND RESULTS: In a model of reentrant ventricular tachycardia (VT) (mean cycle length, 144 +/- 13 msec) around a ring of anisotropic myocardium in 10 Langendorff-perfused rabbit hearts, the effects of extracellular K+ concentration [( K+]o) and heptanol were studied. [K+]o and heptanol each had a dose-dependent effect on VT cycle length. However, high [K+]o slowed the VT mainly by depressing longitudinal conduction, whereas heptanol preferentially depressed transverse conduction. The ratio between longitudinal and transverse conduction velocities progressively decreased with high [K+]o and progressively increased with heptanol. Heptanol terminated VT at a mean concentration of 3.5 +/- 0.5 mM. The cycle length before termination was 446 +/- 120 msec (p less than 0.001). In eight of 10 experiments, termination occurred by failure of conduction during transverse propagation. VT terminated at a mean [K+]o of 11.6 +/- 1.8 mM. The cycle length before termination was 493 +/- 341 msec (p less than 0.01). In seven of 10 cases, termination occurred by failure of conduction during longitudinal propagation. In the remaining five episodes (two with heptanol and three with high [K+]o), termination occurred by collision of the reentrant beat with an antidromic impulse being reflected within the ring. In a separate series of six hearts, tetrodotoxin was administered during VT. Like high [K+]o, tetrodotoxin prolonged the cycle length of the VT by preferentially slowing longitudinal conduction, and VT was terminated by longitudinal block. CONCLUSIONS: During reentrant VT, electrical uncoupling of cells by heptanol or modification of active membrane properties by high [K+]o or tetrodotoxin has a differential depressing effect on propagation of the impulse relative to the fiber orientation.
Alcohols↗
Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias.
BACKGROUND: The goal of this study was to investigate the nature and electrophysiological mechanisms of the proarrhythmic effects of flecainide in Langendorff-perfused rabbit hearts. METHODS AND RESULTS: A thin layer of epicardium was obtained by an endocardial cryotechnique in 10 Langendorff-perfused rabbit hearts. Six other hearts were kept intact. Programmed electrical stimulation using up to three closely coupled premature stimuli and burst pacing was used to test the inducibility of arrhythmias both during control and administration of 1 micrograms/ml flecainide. During control, in the thin layer of epicardium, application of one to three premature stimuli induced nonsustained ventricular tachycardia in out of 10 hearts, and burst pacing induced nonsustained ventricular tachycardia in four hearts and sustained ventricular tachycardia in two hearts. During administration of 1 microgram/ml flecainide, application of one to three premature stimuli induced sustained ventricular tachycardia in five hearts, and burst pacing induced sustained ventricular tachycardia in nine hearts. All tachycardias were based on circus movement of the impulse around arcs of functional block. During administration of flecainide, different locations of the arc of block could be found in the same heart, leading to different reentrant circuits with different cycle lengths. In the control group of six intact hearts, application of up to three closely coupled premature stimuli in all cases induced ventricular fibrillation both during control and administration of flecainide. CONCLUSIONS: Flecainide alters propagation of the impulse in thin surviving layers of myocardium in a manner that facilitates the induction of functionally determined reentry.
Animals↗
Electrophysiology of spiral waves in two dimensions: the role of anisotropy.
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Action Potentials↗
Double-wave reentry as a mechanism of acceleration of ventricular tachycardia.
By using a Langendorff-perfused ring of anisotropic rabbit epicardium, sustained reentrant ventricular tachycardia with a cycle length of 168 +/- 13 msec (n = 26) was induced by programmed electrical stimulation. Continuous left ventricular epicardial mapping with 256 simultaneously recorded unipolar electrograms demonstrated that the tachycardia was based on circuital movement of the impulse around a fixed obstacle. Because of the anisotropic properties of the myocardium, the circuit consisted of a ring with segments in which the circulating wave propagated slowly (20 +/- 2 cm/sec) or faster (62 +/- 4 cm/sec). This was related to transverse or longitudinal propagation in relation to fiber direction. In six of 26 experiments, sudden acceleration in rate of the tachycardia was observed during programmed electrical stimulation. This acceleration was caused by the occurrence of double-wave reentry (two successive waves traveling in the same direction and using the same circuit). In one of the experiments, induction of double-wave reentry was only possible at basal conditions but not after the administration of a class III antiarrhythmic drug. In a seventh experiment, induction of double-wave reentry became possible after the administration of a class IC antiarrhythmic drug. Because conduction velocity around the ring was depressed during acceleration, the total revolution time of the circuit during double-wave reentry was about 120% of that during single-wave reentry. Ventricular tachycardias in which double-wave reentry could be elicited had longer cycle lengths (197 +/- 11 vs. 156 +/- 8 msec, p less than 0.001) and larger excitable gaps (71 +/- 16 vs. 28 +/- 5 msec, p less than 0.001) than those not showing this phenomenon. Double-wave reentry might have important clinical implications in understanding ventricular tachycardia acceleration during programmed electrical stimulation, proarrhythmic effects of drugs, and pathophysiology of rapid ventricular tachycardias.
Animals↗
[Anisotropy and reentrant ventricular tachycardia: experimental model in the isolated rabbit heart].
The purpose of this study was to study the role of anisotropic distribution of conduction velocity in the initiation and perpetuation of ventricular tachycardia in an experimental model of sustained reentrant ventricular tachycardia in the Langendorff perfused rabbit heart. The hearts of 30 rabbits were used in the study. The right ventricle, the interventricular septum and the endocardial and intramural layers of the left ventricle were destroyed by freezing. In the surviving epicardial layer an obstacle was created using a cryoprobe. Thus, the final preparation consisted of a perfused ring of epicardium in the left ventricle. In 27 of 30 experiments programmed electrical stimulation induced sustained reentrant excitation around the obstacle. The cycle length of the tachycardia ranged from 128 to 197 ms in different experiments (mean 162 +/- 17 ms). During tachycardia in some segments of the ring the impulse propagated parallel to fiber orientation at a mean conduction velocity of 61 +/- 7 cm/s whereas in other segments of the ring the impulse propagated perpendicular to fiber orientation at a mean conduction velocity of 22 +/- 4 cm/s. An excitable gap was present during all episodes of tachycardia. In conclusion, conduction velocity during reentrant tachycardia depends on the relation between direction of propagation and fiber orientation. This anisotropic distribution of conduction velocity can play an important role in the initiation and perpetuation of ventricular tachycardia.
Animals↗
Experimental electrophysiology and arrhythmogenicity. Anisotropy and ventricular tachycardia.
In a 2-D model of anisotropy, created by freezing the intramural and endocardial layers of a Langendorf perfused rabbit heart, sustained ventricular tachycardia (VT) with a cycle length of 130 ms and an excitable gap of 30 ms could be initiated by rapid pacing. High resolution mapping (256 points) of the thin surviving epicardial layer revealed that the VT was based on epicardial re-entry without the involvement of a gross anatomic obstacle and a central line of functional conduction block oriented parallel to the fibre. Microelectrode recordings from the centre of the ellipsoid circuit showed markedly prolonged action potentials, leading to 2:1 or 3:1 cellular responses. At the pivoting points prolonged action potentials with a 1:1 response were recorded. Immediately after termination of VT the same sites showed 1:1 responses with normal action potential duration. The various degrees of prolongation of the action potentials in the centre of functional anisotropic re-entry were caused by electrotonic current flow between the two limbs of the circuit, which were closely opposed but activated with a large time difference. Towards the pivoting points the phase difference between the two limbs of the circuit decreased, but because of slow transverse conduction around the pivoting points was still 30 ms. We conclude that the electrotonic prolongation of the action potentials at the pivoting points of anisotropic re-entry enlarges both the size and the cycle length of the circuit. Anisotropy thus contributes to the creation of stable VT with an excitable gap.
Action Potentials↗
A new method for quantitative grip strength evaluation.
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Animals↗