Method for evaluating the effects of antiarrhythmic drugs on ventricular tachycardias with different electrophysiologic characteristics and different mechanisms in the infarcted canine heart

Davis, Jesse C.; Glassman, Robert D.; Wit, Andrew L.

doi:10.1016/0002-9149(82)90042-x

Cited by 34 publications

(2 citation statements)

References 33 publications

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“…The SIS3 coupling interval (horizontal axis) is the coupling interval between the first and second programmed premature beats. on membrane potential, automaticity may or may not be suppressed by overdrive and, when suppressed, it then recurs.38 39 Reentry, like digitalis-induced sustained rhythmic activity, can be terminated by pacing.40 '42 This may occur abruptly on cessation of pacing,41'42 or there may be several "afterbeats" following the cessation of pacing.40 ' 43 It would be useful to obtain precise information about the frequency of afterbeats in reentrant rhythms, since this might help in discriminating between triggered and reentrant rhythms.…”

Section: Discussionmentioning

confidence: 99%

Induction and termination of triggered activity by pacing in isolated canine Purkinje fibers.

Moak¹,

Rosen²

1984

Circulation

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The clinical importance of delayed afterdepolarizations and resultant triggered activity as a cause of cardiac arrhythmias is uncertain. We studied the response of ouabain-induced delayed afterdepolarizations and triggered activity to a pacing protocol similar to those used clinically in an effort to quantify the types of responses to pacing that occur as a result of this arrhythmogenic mechanism. Isolated canine Purkinje fibers were superfused with 2 X 10-7M ouabain until delayed afterdepolarizations occurred and attained an amplitude of 5 mV at a paced cycle length of 500 msec. We then studied the induction of triggered activity in these fibers by pacing. We found that: (I) As the pacing cycle length decreased, the coupling interval from the last paced beat to the first triggered beat decreased and 83% of fibers developed triggered activity. (2) The coupling interval of the first triggered beat after single (S,) or double (S,S) premature beats was in part dependent on preceding pacing cycle lengths. S, pacing induced triggered activity in 39% of fibers, and S S pacing induced triggered activity in 48% of fibers. We then studied the termination of ouabain-induced sustained rhythmic activity by pacing: 89% of sustained rhythmic activity could be terminated by overdrive pacing at a cycle length less than or equal to 300 msec. The coupling interval of the first beat or first delayed afterdepolarization after the termination of overdrive decreased as pacing cycle length decreased. S, premature beats reset the sustained rhythmic activity and terminated 14% of sustained rhythmic activity. The coupling interval of the first escape beat or delayed afterdepolarization after S,S3 premature beats decreased as the S ,S3 interval shortened, and S,S3 terminated 26% of sustained rhythmic activity. Pacing at an S,S, cycle length of 400 msec followed by an S2 terminated 50% of sustained rhythmic activity; S,S, at a cycle length of 400 msec followed by S,S3 terminated 85% of sustained rhythmic activity. This quantitative demonstration of the responses of delayed afterdepolarizations, triggered activity, and sustained rhythmic activity to pacing may be useful in differentiating these from other mechanisms for arrhythmias. Circulation 69, No. 1, 149-162, 1984. TRIGGERED ACTIVITY, defined as impulse initiation induced by afterdepolarizations, has been produced in canine and human Purkinje and ventricular muscle fibers by digitalis,'-' catecholamines,65 and myocardial infarction.9 It also has been produced in canine and human atrial fibers by catecholamines'0' II and digitalis,'2 and in canine coronary sinus by catecholamines. 13

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Section: Discussionmentioning

confidence: 99%

Induction and termination of triggered activity by pacing in isolated canine Purkinje fibers.

Moak¹,

Rosen²

1984

Circulation

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“…Such slow channel action potentials have been implicated in the genesis of reentrant ventricular arrhythmias because of their propensity for very slow propagation of impulses (41,42). In chronic infarcted canine hearts with inducible reentrant ventricular arrhythmia, El-Sherif and Lazzara (43) noted that verapamil could suppress the arrhythmia, whereas Davis et al (44) found that verapamil was totally ineffective. However, El-Sherif and Lazzara (43) Fig.…”

Section: Discussionmentioning

confidence: 99%

Effects of verapamil on ventricular tachycardias possibly caused by reentry, automaticity, and triggered activity.

et al. 1983

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A B S T R A C T To define the role of verapamil in the treatment of ventricular tachycardia (VT), we studied 21 patients with chronic recurrent VT. Electrophysiologic studies were performed before and during intravenous infusion of verapamil (0.15 mg/kg followed by 0.005 mg/kg per min). On the basis of the mode of VT initiation and termination, we identified three groups of patients: (a) 11 patients had VT suggestive of reentry, as VT could be initiated with ventricular extrastimulation and terminated with overdrive ventricular pacing. Verapamil did not affect the inducibility and cycle length of VT. (b) 7 patients had VT suggestive of catecholamine-sensitive automaticity as VT could not be initiated with programmed electrical stimulation but could be provoked by isoproterenol infusion. Moreover, the VT could not be converted to a sustained sinus rhythm with overdrive ventricular pacing and it resolved only with discontinuing isoproterenol infusion. Verapamil exerted no effects on VT. (c) 3 patients had VT with electrophysiologic characteristics suggestive of triggered activity related to delayed afterdepolarizations. Characteristically, after attaining a range of cycle lengths, the sinus, atrial or ventricular paced rhythm could initiate VT without ventricular extrastimulation. The first beat of VT invariably occurred late in the cardiac cycle with a premature coupling interval 0-80 ms shorter than the preceding QRS cycle length; the premature coupling interval gradually decreased as the sinus, atrial or ventricular paced cycle length progressively shortened. Of

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Potassium channels as targets for antiarrhythmic drug action

Colatsky¹,

Follmer²

1990

Drug Development Research

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Colatsky, T.J., and C.H. Follmer: Potassium channels as targets for antiarrhythmic drug action. Drug Dev. Res. 19:129-140, 1990.Recent cellular electrophysiologic studies have begun to clarify the basis of antiarrhythmic drug action. The Class I agents have been shown to block cardiac sodium channels in a use-dependent manner, and the kinetics and potency of sodium channel block correlated with molecular weight and lipid solubility of drug. The Class IA agents, like quinidine, which increase cardiac action potential duration and refractory period in addition to their effects on conduction, also appear to have potent blocking actions on the potassium channels responsible for repolarization in myocardial cells, whereas the Class IB agents, like lidocaine, shorten action potential duration and are relatively specific in their block of sodium channels. In contrast, Class Ill agents, which prolong the action potential without slowing conduction, appear to exert their primary blocking action on the potassium channel only. Conversion from Class I to Class Ill electrophysiologic profiles can be achieved by the substitution of electron-withdrawing groups (e.g., NO, ) in place of electron-donating groups (e.g., NH, ) on the aromatic portion of the basic local anesthetic pharmacophore. Class Ill agents appear to be most effective against ventricular fibrillation and ventricular tachycardia due to re-entry, but are generally without activity in the 24 hr Harris dog arrhythmia model.Further evaluation of the mechanism of antiarrhythmic drug action will require use of welldefined arrhythmia models in a combination with a detailed understanding of drug-channel interactions.

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Method for evaluating the effects of antiarrhythmic drugs on ventricular tachycardias with different electrophysiologic characteristics and different mechanisms in the infarcted canine heart

Cited by 34 publications

References 33 publications

Induction and termination of triggered activity by pacing in isolated canine Purkinje fibers.

Induction and termination of triggered activity by pacing in isolated canine Purkinje fibers.

Effects of verapamil on ventricular tachycardias possibly caused by reentry, automaticity, and triggered activity.

Potassium channels as targets for antiarrhythmic drug action

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