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

Amara Greer-Short,Steven Poelzing

doi:10.3389/fphys.2015.00014

Abstract

Rapid ventricular pacing rates induces two types of beats following pacing cessation: recovery cycle length (RCL) prolongation (overdrive suppression) and RCL shortening (overdrive excitation). The goals of this study were to compare common experimental protocols for studying triggered activity in whole-heart preparations and differentiate between recovery beats using a new methodology. Post-pacing recovery beat cycle length (RCL) and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced suppressed beats: RCL ratio increased with rapid pacing (25 ± 4.0%, n = 10) without changing QRS duration. Rapid pacing during hypercalcemia + hypothermia (5.5 mM and 34°C) produced significantly earlier excited beats (53 ± 14%, n = 5) with wider QRS durations (58 ± 6.3%, n = 5) than suppressed beats. Digoxin + hypothermia (0.75 μM) produced the most excited beats with significantly earlier RCL (44 ± 3.2%, n = 6) and wider QRS (60 ± 3.1%, n = 6) ratios relative to suppressed beats. Increasing pacing further shortened RCL (30 ± 7.8%, n = 6). In a prospective study, TTX (100 nM) increased RCL ratio (15 ± 6.0%, n = 10) without changing the QRS duration of excited beats. The algorithm was compared to a cross-correlation analysis with 93% sensitivity and 94% specificity. This ECG based algorithm distinguishes between triggered and automatic activity.

Highlights

The heart electrically excites and contracts in a specific order, as automaticity in sino-atrial nodal cells sets a rhythm faster than other cardiac cells
The QRS complexes of the recovery beat in the control hearts in Figure 1A appear similar, while the digoxin recovery beats at 375 bpm exhibit variable ECG characteristics
At 375 bpm, recovery cycle length (RCL) significantly decreased to 388 ms but the standard deviation significantly increased to 154 ms

Summary

Introduction

The heart electrically excites and contracts in a specific order, as automaticity in sino-atrial nodal cells sets a rhythm faster than other cardiac cells. Work in canine purkinje fibers using cardiac glycosides found premature low amplitude membrane depolarizations following rapid pacing (Ferrier et al, 1973; Hashimoto and Moe, 1973; Rosen et al, 1973). Close observation led to the discovery that the onset of these small depolarizations in Purkinje fibers were concordant with the onset of ventricular arrhythmias (Rosen et al, 1973) This suggested that small depolarizations may be responsible for cardiac glycoside-induced ventricular arrhythmias. These depolarizations, later known as delayed afterdepolarizations (DADs), could initiate an action potential if the amplitude was large enough (Ferrier et al, 1973).

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