The actions of lidocaine were studied in 18 dogs, 4 days after ligation of the left anterior descending artery, by computerized mapping. Lidocaine only occasionally suppressed the induction of reentry. At fast heart rates, lidocaine actually facilitated the induction of reentry. The effects on conduction and refractoriness of normal and ischemic myocardium were measured using high-resolution techniques. Lidocaine promoted reentry by a rate-dependent increase in refractory gradient, resulting in additional block, and a selective decrease in conduction velocity in ischemic tissue, resulting in additional conduction delay. Lidocaine could prevent reentry through a rate-independent differential increase in refractory period gradient at the entrance to the common pathway of the circuit, causing block of the reentrant impulse. We conclude that the proarrhythmic effect of lidocaine is due to increased conduction delay and block while the antiarrhythmic effect is due to block of the reentrant impulse by prolonged refractoriness in the common pathway.
Al-Zakhari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Because flecainide caused no significant change in refractoriness in both normal and ischemic myocardia, there was no difference in the dimension of the potential reentrant pathway, that is, the continuous line of functional conduction block, around which the reentrant wave fronts circulate. Yet, flecainide resulted in significant rate-dependent slowing of conduction preferentially in ischemic myocardium. The additional slowing of conduction of the common reentrant wave front coupled with minimal changes in the length of the reentrant pathway allowed additional time for the wave front to reexcite normal myocardium on the proximal side of the arc of block. After flecainide, reentry could be induced in hearts in which reentry could not be induced during control. The same proarrhythmic mechanism explains the propensity of nonsustained figure-8 reentrant tachycardias to become sustained after flecainide.
The present study demonstrated that the combination of glucose and insulin is essential for the salutary effect of reducing [K+]o accumulation during ischemia and improving the associated intramyocardial conduction delay. It could be postulated that glucose in the presence of insulin increases the glycolytic flux, thereby providing adequate adenosine triphosphate for suppressing the cardiac adenosine triphosphate-sensitive potassium ion channels. The latter are, at least partially, responsible for the [K+]o rise in the early phase of ischemia. This study highlights the antiarrhythmic potential of interventions that modulate the metabolic consequences of ischemia.
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