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The persistent sodium current blocker riluzole is antiarrhythmic and anti-ischaemic in a pig model of acute myocardial infarction.

Weiss SM, Saint DA - PLoS ONE (2010)

Bottom Line: QRS and QTc did not change appreciably in any group Riluzole reduced the degree of histopathological tissue damage across the infarct zone considerably more than did lidocaine.At the doses used, riluzole was at least as effective as lidocaine at reducing the number of episodes of ischaemic VT or VF in pigs, and much more effective at reducing the number of PVCs.We propose that this is related to the ability of riluzole to block cardiac persistent sodium current.

View Article: PubMed Central - PubMed

Affiliation: Australian National University, Canberra, Australia.

ABSTRACT

Background: The potential of the cardiac persistent sodium current as a target for protection of the myocardium from ischaemia and reperfusion injury is gaining increasing interest. We have investigated the anti-ischaemic and antiarrhythmic effects of riluzole, a selective INaP blocker, in an open chest pig model of infarction.

Methods and principal findings: The left anterior descending coronary artery (LAD) was ligated in 27 anesthetised pigs (landrace or large white, either sex, 20-35 kg) which had received riluzole (8 mg/kg IP; n = 6), lidocaine (2.5-12 mg/kg bolus plus 0.05-0.24 mg/kg/min; n = 11) or vehicle (n = 10) 50 min prior. Arrhythmias could be delineated into phase 1a (0 to 20 min), phase 1b (20 to 50 min) and phase 2 (from 50 min to termination at 180 min) and were classified as premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) (spontaneously reverting within 15 s) or sustained VT or VF (ie. requiring cardioversion at 15 s). Riluzole reduced the average number of all arrhythmias in Phase 2 (PVCs from 484+/-119 to 32+/-13; non sustained arrhythmias from 8.9+/-4.4 to 0.7+/-0.5; sustained arrhythmias from 3.9+/-2.2 to 0.5+/-0.4); lidocaine reduced the average number of non-sustained and sustained arrhythmias (to 0.4+/-0.3 and 0.4+/-0.3 respectively) but not PVCs (to 390+/-234). Riluzole and lidocaine reduced the average number of sustained arrhythmias in phase 1b (from 1.8+/-0.4 to 0.17+/-0.13 (p<0.02) and to 0.55+/-0.26 (p = ns) respectively). Neither lidocaine or riluzole changed the ECG intervals: there was no statistical significance between groups at time zero (just before ligation) for any ECG measure. During the course of the 3 hour period of the ischaemia R-R, and P-R intervals shortened slightly in control and riluzole groups (not significantly different from each other) but not in the lidocaine group (significantly different from control). QRS and QTc did not change appreciably in any group Riluzole reduced the degree of histopathological tissue damage across the infarct zone considerably more than did lidocaine.

Conclusions: At the doses used, riluzole was at least as effective as lidocaine at reducing the number of episodes of ischaemic VT or VF in pigs, and much more effective at reducing the number of PVCs. We propose that this is related to the ability of riluzole to block cardiac persistent sodium current.

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Related in: MedlinePlus

Time course of ECG intervals.Plots of R-R, P-R, QRS and QTc intervals during the experiment. Data are shown for 30, 60, 90, 120, 150 and 180 min after ligation (points are displaced for clarity). Symbols show mean +/− SEM. Control  =  filled circles, riluzole  =  filled squares, lidocaine  =  filled triangles.
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pone-0014103-g004: Time course of ECG intervals.Plots of R-R, P-R, QRS and QTc intervals during the experiment. Data are shown for 30, 60, 90, 120, 150 and 180 min after ligation (points are displaced for clarity). Symbols show mean +/− SEM. Control  =  filled circles, riluzole  =  filled squares, lidocaine  =  filled triangles.

Mentions: ECG intervals were not significantly different between the groups after drug administration and before ligation. During the course of the 3 hour period of ischaemia R-R intervals shortened slightly in control and riluzole treated animals (p <0.001) but this was not seen in the lidocaine treated animals. Similar results were seen with P-R interval; a slight shortening in control and riluzole treated animals which was not seen in the lidocaine group QRS and QTc did not change appreciably during the course of the 3 hour ischaemia in any group. (figure 4)


The persistent sodium current blocker riluzole is antiarrhythmic and anti-ischaemic in a pig model of acute myocardial infarction.

Weiss SM, Saint DA - PLoS ONE (2010)

Time course of ECG intervals.Plots of R-R, P-R, QRS and QTc intervals during the experiment. Data are shown for 30, 60, 90, 120, 150 and 180 min after ligation (points are displaced for clarity). Symbols show mean +/− SEM. Control  =  filled circles, riluzole  =  filled squares, lidocaine  =  filled triangles.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2991348&req=5

pone-0014103-g004: Time course of ECG intervals.Plots of R-R, P-R, QRS and QTc intervals during the experiment. Data are shown for 30, 60, 90, 120, 150 and 180 min after ligation (points are displaced for clarity). Symbols show mean +/− SEM. Control  =  filled circles, riluzole  =  filled squares, lidocaine  =  filled triangles.
Mentions: ECG intervals were not significantly different between the groups after drug administration and before ligation. During the course of the 3 hour period of ischaemia R-R intervals shortened slightly in control and riluzole treated animals (p <0.001) but this was not seen in the lidocaine treated animals. Similar results were seen with P-R interval; a slight shortening in control and riluzole treated animals which was not seen in the lidocaine group QRS and QTc did not change appreciably during the course of the 3 hour ischaemia in any group. (figure 4)

Bottom Line: QRS and QTc did not change appreciably in any group Riluzole reduced the degree of histopathological tissue damage across the infarct zone considerably more than did lidocaine.At the doses used, riluzole was at least as effective as lidocaine at reducing the number of episodes of ischaemic VT or VF in pigs, and much more effective at reducing the number of PVCs.We propose that this is related to the ability of riluzole to block cardiac persistent sodium current.

View Article: PubMed Central - PubMed

Affiliation: Australian National University, Canberra, Australia.

ABSTRACT

Background: The potential of the cardiac persistent sodium current as a target for protection of the myocardium from ischaemia and reperfusion injury is gaining increasing interest. We have investigated the anti-ischaemic and antiarrhythmic effects of riluzole, a selective INaP blocker, in an open chest pig model of infarction.

Methods and principal findings: The left anterior descending coronary artery (LAD) was ligated in 27 anesthetised pigs (landrace or large white, either sex, 20-35 kg) which had received riluzole (8 mg/kg IP; n = 6), lidocaine (2.5-12 mg/kg bolus plus 0.05-0.24 mg/kg/min; n = 11) or vehicle (n = 10) 50 min prior. Arrhythmias could be delineated into phase 1a (0 to 20 min), phase 1b (20 to 50 min) and phase 2 (from 50 min to termination at 180 min) and were classified as premature ventricular contractions (PVCs), non-sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) (spontaneously reverting within 15 s) or sustained VT or VF (ie. requiring cardioversion at 15 s). Riluzole reduced the average number of all arrhythmias in Phase 2 (PVCs from 484+/-119 to 32+/-13; non sustained arrhythmias from 8.9+/-4.4 to 0.7+/-0.5; sustained arrhythmias from 3.9+/-2.2 to 0.5+/-0.4); lidocaine reduced the average number of non-sustained and sustained arrhythmias (to 0.4+/-0.3 and 0.4+/-0.3 respectively) but not PVCs (to 390+/-234). Riluzole and lidocaine reduced the average number of sustained arrhythmias in phase 1b (from 1.8+/-0.4 to 0.17+/-0.13 (p<0.02) and to 0.55+/-0.26 (p = ns) respectively). Neither lidocaine or riluzole changed the ECG intervals: there was no statistical significance between groups at time zero (just before ligation) for any ECG measure. During the course of the 3 hour period of the ischaemia R-R, and P-R intervals shortened slightly in control and riluzole groups (not significantly different from each other) but not in the lidocaine group (significantly different from control). QRS and QTc did not change appreciably in any group Riluzole reduced the degree of histopathological tissue damage across the infarct zone considerably more than did lidocaine.

Conclusions: At the doses used, riluzole was at least as effective as lidocaine at reducing the number of episodes of ischaemic VT or VF in pigs, and much more effective at reducing the number of PVCs. We propose that this is related to the ability of riluzole to block cardiac persistent sodium current.

Show MeSH
Related in: MedlinePlus