Effects of Late Sodium Current Blockade on Ventricular Refibrillation in a Rabbit Model.

BACKGROUND

After defibrillation of initial ventricular fibrillation (VF), it is crucial to prevent refibrillation to ensure successful resuscitation outcomes. Inability of the late Na current to inactivate leads to intracellular Ca dysregulation and arrhythmias. Our aim was to determine the effects of ranolazine and GS-967, inhibitors of the late Na current, on ventricular refibrillation.

METHODS AND RESULTS

Long-duration VF was induced electrically in Langendorff-perfused rabbit hearts (n=22) and terminated with a defibrillator after 6 minutes. Fibrillating hearts were randomized into 3 groups: treatment with ranolazine, GS-967, or nontreated controls. In the treated groups, hearts were perfused with ranolazine or GS-967 at 2 minutes of VF. In control experiments, perfusion solution was supplemented with isotonic saline in lieu of a drug. Inducibility of refibrillation was assessed after initial long-duration VF by attempting to reinduce VF. Sustained refibrillation was successful in fewer ranolazine-treated (29.17%; =0.005) or GS-967-treated (45.83%, =0.035) hearts compared with that in nontreated control hearts (84.85%). In GS-967-treated hearts, significantly more spontaneous termination of initial long-duration VF was observed (66.67%; =0.01). Ca transient duration was reduced in ranolazine-treated hearts compared with that in controls (=0.05) and also Ca alternans (=0.03).

CONCLUSIONS

Late Na current inhibition during long-duration VF reduces the susceptibility to subsequent refibrillation, partially by mitigating dysregulation of intracellular Ca. These results suggest the potential therapeutic use of ranolazine and GS-967 and call for further testing in cardiac arrest models.