Mechanisms of resetting reentrant circuits in canine ventricular tachycardia.

BACKGROUND: Resetting has been used to characterize reentrant circuits causing clinical tachycardias. METHODS AND RESULTS: To determine the mechanisms of resetting, sustained ventricular tachycardia was induced in dogs with 4-day-old myocardial infarctions by programmed stimulation. Premature stimulation was accomplished from multiple regions within reentrant circuits; resetting curves were constructed and compared with activation maps. Monotonically increasing responses, or a "mixed" response (increasing portion preceded by a flat portion), occurred. All reentrant circuits had a fully excitable gap. Interval-dependent conduction delay and concealed retrograde penetration led to increased resetting response curves. CONCLUSIONS: Multiple mechanisms revealed by mapping cause resetting of reentrant circuits.

Characteristics of the temporal and spatial excitable gap in anisotropic reentrant circuits causing sustained ventricular tachycardia.

The excitable gap of a reentrant circuit has both temporal (time during the cycle length that the circuit is excitable) and spatial (length of the circuit that is excitable at a given time) properties. We determined the temporal and spatial properties of the excitable gap in reentrant circuits caused by nonuniform anisotropy. Myocardial infarction was produced in canine hearts by ligation of the left anterior descending coronary artery. Four days later, reentrant circuits were mapped in the epicardial border zone of the infarcts with a multielectrode array during sustained ventricular tachycardia induced by programmed stimulation. During tachycardia, premature impulses were initiated by stimulation at sites around and in the reentrant circuits, and their conduction characteristics in the circuit were mapped. All circuits had a temporal excitable gap in at least part of the circuit, which allowed premature impulses to enter the circuit. Completely and partially excitable segments of the temporal gap were identified by measuring conduction velocity of the premature impulses; conduction was equal to the native reentrant wave front in completely excitable regions and slower than the reentrant wave front in partially excitable regions. In some circuits, a temporal gap existed throughout the circuit, permitting the entire circuit to be reset over a range of premature coupling intervals, although the size of the gap varied at different sites. In other circuits, the gap became so small at local sites that even though premature impulses could enter the circuit, the circuit could not be reset. Premature impulses could terminate reentry in circuits that could be reset or not. We also found a significant spatial gap, which was identified by determining the distance between the head of the circulating wave front, which could be located on the activation map, and its tail, which was the site most distal from the head as located by the site of entry of the premature wave front into the circuit. The spatial gap could also vary in different parts of the circuit. Therefore, nonuniform anisotropic reentrant circuits have both a temporal and spatial excitable gap with fully and partially excitable components that change in different parts of the circuit.

Inappropriate pauses during bradycardia pacing in a third-generation implantable cardioverter defibrillator.

Many ICD devices have the capability for back up bradycardia pacing. Because of the use of a single sensing algorithm for both bradycardia and tachycardia functions, they may be prone to certain "sensing errors." Following implantation of an ICD in a patient with long QT syndrome, "inappropriate" pauses were noted during bradycardia pacing, which were exactly twice the programmed pacing cycle length. This was due to an automatic increase in the device's sensitivity during pacing, a characteristic of the automatic gain control of this particular ICD. Proper recognition of this ICD's special features, known as "lower threshold crossing," allowed noninvasive rectification of the problem and prevented these pauses.

Termination of reentry by lidocaine in the tricuspid ring in vitro. Role of cycle-length oscillation, fast use-dependent kinetics, and fixed block.

We hypothesized that drugs with rapid recovery kinetics from use-dependent sodium channel block could promote oscillatory termination of reentry by enhancing interval-dependent conduction. Mechanisms of termination were related to properties of the reentrant circuit. Nine adjustable reentrant preparations were used in which the canine atrial tricuspid ring was cut and then reconnected electronically by sensing activation on one side of the cut and pacing the other after an adjustable delay. The cycle length and diastolic interval during reentry were manipulated by changing this delay. Lidocaine (1.28 x 10(-5) mol/L) significantly increased refractoriness (94 +/- 39 ms) and the slope of the conduction curve (-0.12 +/- 0.07) at the site of block during pacing. Lidocaine terminated sustained reentry by two mechanisms. Early termination resulted from increased cycle length oscillation and refractoriness (reproducible in each experiment) but only at short delays with short initial diastolic intervals. The range of delays showing this mechanism of termination was 100 +/- 48 ms. Increased cycle-length oscillation resulted from an increased slope of the conduction curve. In eight experiments, lidocaine terminated reentry by causing fixed block after 50 minutes of drug superfusion, which prevented reentry at all delays. Fixed block occurred at one of two vulnerable sites and was transiently reversed by acetylcholine. Termination due to refractory block occurred only when the initial diastolic interval was short, and termination due to fixed block developed when there was a susceptible region with a low safety factor for propagation. Fast recovery from sodium channel block promotes oscillatory termination by increasing the slope of the conduction curve.

Assessing the excitable gap in reentry by resetting. Implications for tachycardia termination by premature stimuli and antiarrhythmic drugs.

BACKGROUND: The shortest excitable gap during reentry may determine responses to pacing and antiarrhythmic drugs. The resetting response has been used clinically to assess the excitable gap, but it cannot directly indicate the shortest excitable gap. METHODS AND RESULTS: We studied resetting in the in vitro canine atrial tricuspid ring using an adjustable reentry preparation in which the ring was cut and reconnected electronically with an adjustable delay to vary the cycle length and excitable gap. We reset the tachycardias using 31 delays in 12 experiments. Tachycardias were terminated by premature stimuli in 16 delays. The reset window overestimated the shortest excitable gap by 25 +/- 14 ms, and the maximum degree of advancement of tachycardia underestimated the shortest excitable gap by 22 +/- 11 ms. The slope of the increasing portion of the resetting response curve was steeper in tachycardias terminated by premature stimuli than in those not terminated (-0.69 +/- 0.2 versus -0.37 +/- 0.2, P < .01). The effective refractory period difference between the sites of pacing and of block correlated with the slope of the resetting response curve. Damped cycle length oscillation after a long return cycle during resetting was always present when there was a partially excitable gap. CONCLUSIONS: The reset window during pacing within the circuit and the maximum degree of advancement provided equally good estimates bracketing the shortest excitable gap. The slope of the resetting response curve predicted the likelihood of termination by premature stimuli. Damped cycle length oscillation after resetting detected a partially excitable gap.

Acute and chronic cycle length dependent increase in ventricular pacing threshold.

Several factors have been shown to influence ventricular pacing threshold in humans, including pacing lead location (endocardial vs epicardial), lead maturation, and antiarrhythmic agents. To determine whether ventricular pacing rate has a significant influence on acute and chronic pacing thresholds, we measured pacing thresholds in 16 patients receiving an implantable antitachycardia pacemaker cardioverter defibrillator (Cadence). Ventricular pacing thresholds were determined using the device programmer at cycle lengths of 600, 400 and 300 msec at the time of implantation; prior to hospital discharge at 3-14 days; and during follow-up outpatient visits at 6-8 weeks, 3 months, and 6 months to 1 year. Eleven patients had an epicardial lead system and five an endocardial lead system. Eleven patients were being treated with antiarrhythmic drug therapy. Device output ranged from 1-10 V and was adjustable in 1-V increments (pulse width was held constant at 1 msec). A cycle length dependent increase in pacing threshold (defined as a > or = 1-V increase in threshold at 400 or 300 msec relative to 600 msec) was observed in 10/16 patients during 12/72 pacing trials at 400 msec, and in 15/16 patients during 31/67 trials at 300 msec. In trials in which an increase in pacing threshold occurred, the magnitude of the increase at 400 msec relative to 600 msec was only 1 V in all 12 trials, but at 300 msec the increase ranged from 4-9 V in 7/31 (23%) trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Time course of changes in intracellular K+, Na+, and pH of subendocardial Purkinje cells during the first 24 hours after coronary occlusion.

We investigated the basis for the alterations in the intracellular potassium and sodium activity occurring in subendocardial Purkinje fibers surviving in 24-hour infarcts by examining ion activities in these Purkinje fibers removed from infarcting hearts at earlier times. Specifically, we examined intracellular potassium activity, sodium activity, and pH at 1 and 3 hours after ligation of the left anterior descending coronary artery, and we correlated the changes in ion activity with changes in maximum diastolic potential. We tested various mechanistic hypotheses relating to how the ion activity changes develop and how they affect membrane potential. We found that intracellular sodium activity in tissue removed 1 hour after ligation was on average already maximally elevated by a factor of 2 over control (19.2 +/- 2.0 mM [mean +/- SEM] versus 9.4 +/- 0.4 mM). Potassium activity diminished progressively over the first 24 hours (from normal of 112.0 +/- 2.7 to 61.6 +/- 2.8 mM), although half of the decrease occurred during the first hour (to 86.8 +/- 4.1 mM). Intracellular pH did not change at either 1 or 3 hours. Whereas maximum diastolic potential depolarization exceeded the calculated depolarization of the potassium equilibrium potential by a factor of 2 in 24-hour infarcts, the depolarization at 1 and 3 hours could be more nearly attributed to the loss of potassium. The change in the dependence of maximum diastolic potential on potassium equilibrium potential may be due to changes in membrane conductance caused by ionic or biochemical factors. The changes in ion activity continuously develop during the first day after ligation and may be due to multiple factors and mechanisms.