Premature escape beats. A model for triggered activity in the intact heart?

Abstract

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...

Distinguishing between overdrive excited and suppressed ventricular beats in guinea pig ventricular myocardium

“…Our methodology utilized both normalizing the recovery beat cycle length to the pre-paced beat cycle length and the recovery beat QRS duration to the pre-paced beat QRS duration. The finding that OE beat RCL ratios reduced in response to increased pacing rate is consistent with previous reports of similar measurements using normalized recovery beat cycle length to post-pacing R-R interval as a mechanistic stratifier (Vos et al, 1990 ). Indeed, RCL and RCL ratio for OE beats were significantly smaller when compared to OS beats, consistent with OE beat behavior.…”

“…Rapid pacing is known to induce two types of recovery beats following the cessation of pacing: an interval of quiescence greater than or equal to the native rhythm, or a shortened interval. While we recapitulated previous studies demonstrating that RCL is proportional to pacing rate under control conditions (Malfatto et al, 1988 ; Iinuma et al, 1989 ) and inversely proportional during perfusion with a cardiac glycoside (Malfatto et al, 1988 ; Vos et al, 1990 ), the relationship observed for digoxin in Figure 1B may be misleading. More precisely, our beat classification system demonstrates that two distinct mechanistic populations compose recovery beats.…”

“…Later observations in intact heart models discovered that glycosides decreased recovery beat cycle length following rapid pacing (Malfatto et al, 1988 ; Vos et al, 1990 ), suggesting that triggered recovery beats in intact models with glycoside toxicity were due to TA, as their behavior was consistent with data from Purkinje fibers. More generally speaking, cardiac glycosides and many other interventions such as hypercalcemia (Plummer et al, 2011 ), catecholamine perfusion (Priori and Corr, 1990 ), and myocardial infarction (Lazzara et al, 1973 ) are associated with an increased incidence of DADs and TA.…”

“…Previous methods for analyzing triggered activity (TA) in whole hearts have included analyzing recovery beats: (1) of ventricular origin, (2) that have a shorter cycle length than the longest post-paced R-R interval, (3) with preceding delayed afterdepolarizations (DADs), or (4) with preceding spontaneous calcium releases (Malfatto et al, 1988 ; Furukawa et al, 1990 ; Vos et al, 1990 ; Plummer et al, 2011 ). The use of raw RCL and QRS values resulted in preferentially clustering based on RCL values.…”

Programmed electrical stimulation and drugs identify two subgroups of ventricular tachycardias occurring 16-24 hours after occlusion of the left anterior descending artery.

“…This behavior has been described to be specific for VTs resulting from DADs. [36][37][38][39] In the PS group, an increase in the first postpacing interval was expected when the interstimulus interval was reduced and/or the duration of pacing was increased.23 This behavior typical for overdrive suppression was only clearly present after changing the duration of pacing. Decreasing the interstimulus interval from 400 to 300 msec resulted in the expected lengthening of the first postpacing interval.…”