Order in disorder: effect of barium on ventricular fibrillation.
BACKGROUND
Drugs that prolong cardiac refractoriness can decrease defibrillation energy requirements. In particular, barium, a relatively selective blocker of cardiac Ik1 channels, produces marked decreases in defibrillation energy. The mechanism of this effect is unknown, and may relate to modulation of the effect of defibrillatory shocks, or an alteration of the pattern of ventricular fibrillation (VF) by the drug.


RESULTS
Accordingly, the effect of barium chloride was examined, 1.1 mg/kg followed by 0.1 mg/kg/min intravenously, or saline control, on the pattern of unipolar electrograms using a 120 electrode array, during 73 episodes of VF (37 after saline, 36 after barium ). For each episode of VF, peak-dV/dt associated with local activations and mean activation-activation (ACT-ACT) intervals for the last 2 s of a 10 s episode of VF were measured for each electrode. 'Organization' in VF was measured by the variability in ACT-ACT intervals, their visually assessed pattern, and the relation between local activations on adjacent electrodes. Voltage gradients were measured at each of 40 epicardial sites for each defibrillation shock, delivered at voltages ranging from to 20% to 100% successful in defibrillation. At identical voltage shocks (400 V), mean voltage gradients before and after barium were similar: 18+/-9 and 19+/-1.2 V/cm, respectively. Mean peak -dV/dt for all activations was -8.7+/-0.5 V/s before and -7.7+/-2.8 V/s after barium, suggesting no apparent change in local conduction velocity. When the lowest voltage gradient at any site was less than 3.5 V/cm, defibrillation was successful 14% of the time (two of 14 ) during control, but 88% of the time (14 to 16) after barium infusion (P<0.01). Mean ACT-ACT intervals after barium for all episodes over all electrodes was 107.5+/-14.1 ms, significantly longer than 89.7 +/-3.9 ms after saline, indicating a 20% increase in the cycle length of fibrillation. During saline control, local epicardial electrogram patterns showed irregular, variable morphology electrograms and a mean lowest SD of ACT-ACT intervals over any electrode of 5.1+/-1.5 ms, compared with 1.2+/-0.7 ms after barium (P < 0.0001). Following barium, most unipolar epicardial electrograms showed regular, phasic activations that appear to reflect an organized, uniformly repetitive local activation pattern, suggesting spatially homogeneous and temporally regular activation wavefronts.


CONCLUSIONS
During VF after barium, despite an apparently disorganized surface electrocardiographic pattern, epicardial electrogram patterns are altered and reflect a more ¿ordered', homogeneous and regular local activation. This increased order may be in part responsible for the decreased defibrillation energy requirements observed after barium.
Dorian
P
P
Department of Medicine, University of Toronto, Ontario. dorianp@smh.toronto.on.ca
Penkoske
P A
PA
Witkowski
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FX
D000818:Animals; D001466:Barium Sulfate / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004554:Electric Countershock; D004562:Electrocardiography; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000628:therapy*
D001466:Barium Sulfate