In isolated Purkinje fibers, digitalis intoxication induces triggered activity, which is based upon delayed afterdepolarizations. The characteristics of delayed afterdepolarizations have been studied systematically by programmed electrical stimulation. The present investigations were done to study the role of triggered activity during digitalis intoxication in the intact heart. For this purpose, a pacing protocol, similar to that used in experiments of isolated Purkinje fibers, was used. The experiments were done on conscious dogs with chronic complete atrioventricular block. Ventricular tachycardia was induced with digoxin IV 0.1 mg/kg/1-1 1/2 hr. The effect of programmed electrical stimulation on the first post-pacing interval was determined during sustained ventricular tachycardia and, following its spontaneous termination during an episode when ectopic activity could only be induced by pacing. During sustained ventricular tachycardia there was a direct linear relation between the interstimulus interval of regular pacing and the first post-pacing interval. During the episode when ectopic activity could only be induced by pacing, shortening of the post-pacing interval resulted in biphasic behavior of the first post-pacing interval. Pacing with interstimulus intervals of more than 400 ms induced a first post-pacing interval equal to the interstimulus interval, whereas shorter interstimulus intervals induced a first post-pacing interval twice the interstimulus interval. When during regular pacing only the last pacing interval was changed, a similar biphasic response resulted. When toxicity had almost subsided, ectopic activity could only be induced following short pacing intervals (200-320 ms). Again, a direct linear relation was found between the pacing interval and the first post-pacing interval. Our findings strongly suggest that at different levels of digitalis intoxication triggered activity is the underlying mechanism for the first post-pacing QRS complex.
In conscious dogs with complete atrioventricular block, overdrive pacing of the idioventricular rhythm normally results in overdrive suppression (OS). Frequently, however, we observed another response to overdrive, that is, QRS complex or complexes with unexpectedly short coupling intervals followed by normal OS. We have named such a QRS complex a "premature escape beat" (PEB). Based on the response of PEBs to electrical stimulation, we postulate that PEBs are based on triggered activity resulting from delayed afterdepolarizations. This hypothesis was tested in 82 experiments by 1) stimulation under control conditions and in combination with 2) subtoxic and toxic amounts of ouabain 20-50 jig/kg, 3) lidocaine 3 mg/kg, and 4) doxorubicin 16-24 mg/M2. The stimulation protocol, which was repeated at random five to 10 times, consisted of 10 and 50 stimuli using interstimulus intervals of 200, 400, 600, and 800 msec. This protocol was not only performed during spontaneous idioventricular rhythm but also during a continuously paced rhythm with interstimulus intervals of 800 msec. It was found that 1) the chance to induce a PEB or PEBs increased and 2) their first postpacing interval significantly decreased using short or fast drives, or both. Ouabain increased significantly and in a dose-dependent manner 1) the ability to induce PEBs and 2) the number of PEBs per stimulation-train, and also shortened their first postpacing interval. Opposite effects were seen after lidocaine, doxorubicin, and continuous pacing as follows: 1) a lower incidence of PEBs and 2) lengthening of their first postpacing interval. These results support our hypothesis that PEBs are based on triggered activity resulting from delayed afterdepolarizations. (Circulation 1990;82:213-224) W hile studying the response of ouabaininduced ventricular tachycardia (VT) to electrical stimulation in conscious dogs,1 we noticed that initiation of "triggered" beats by pacing was possible in the absence of ouabain (Figure 1). We have termed these QRS complexes with unexpectedly short coupling intervals "premature escape beats" (PEBs). Their occurrence is in contrast to the phenomenon of overdrive suppression, which is normally seen when an idioventricular rhythm is overpaced.2 The amount of overdrive suppression is dependent on rate and duration of stimulation34 and is followed by slow acceleration of the ventricular rate until prepacing values are attained.Based on the response of PEBs to electrical stimulation, we considered the possibility that PEBs are based on triggered activity resulting from delayed afterdepolarizations (DADs mechanism has been most extensively investigated in the setting of digitalis intoxication.5-8 Other interventions inducing DADs have also been described, like catecholamines,9,10 hypopotassemia,1""2 after myocardial infarction, '1314 during reperfusion,15,16 and hypertrophy.17 DADs have been demonstrated to result from intracellular calcium overload.8'8 Resulting arrhythmias have the following characteristics in common ,5-01,1...
During digitalis-induced, sustained, monomorphic ventricular tachycardia, programmed electrical stimulation was performed and the effect on the first post-pacing QRS morphology was determined. Ventricular tachycardia was induced in nine conscious dogs with chronic complete atrioventricular block by administering digoxin i.v. 0.1 mg/kg given in 1-1 1/2 hour. Spontaneous ventricular tachycardia most frequently had a right bundle branch block morphology and an extreme left axis suggesting an origin in the apex of the left ventricle. Less frequently, a left bundle branch block-like configuration with an intermediate axis was observed, compatible with an origin in the basal part of the right ventricle. Following pacing close to one of these predilection sites, the first post-pacing QRS morphology suggested an origin close to the site of stimulation. Pacing distant from these predilection sites resulted in fusion complexes between electrical activation from these predilection sites and the stimulation site. The amount of fusion depended on interstimulus interval and the number of stimuli. Long interstimulus intervals and few stimuli induced a QRS complex similar to that of the spontaneous tachycardia. The faster and longer the stimulation train, the more the QRS complex became similar to the paced QRS complex. Similar findings were also observed on decreasing the last paced interval only. Our findings suggest that triggered activity is the underlying mechanism for the first post-pacing QRS complex. QRS configuration and the relation between the R-R interval and QRS configuration during tachycardia suggest that triggered activity is also the mechanism for the spontaneously occurring ventricular tachycardia during digitalis intoxication. These observations may have important clinical implications.
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