Modulation by the n-6 to n-3 PUFA ratio of cardiac phospholipids of the anti-arrhythmic effects of lidocaine

Comunication orale : Demaison L.Comunication orale : Demaison L.; Background: Enrichment of cardiac phospholipids with eicosapentaenoic acid (EPA) is known to be cardioprotective during ischemia/reperfusion. This study aimed at studying the effect of dietary EPA-rich fish oil on the occurrence of severe reperfusion arrhythmias, at determining if the anti-arrhythmic lidocaine modulates that effect and at trying to evaluate the mechanism of these treatments. Materials and Methods: Rats were fed two diets differing in their PUFA composition for 8 weeks. The first one contained 10% of sunflower seed oil (SSO) and the second one 5% of fish oil (FO) plus 5% of SSO. The hearts were then perfused according to the working mode with a perfusion medium containing or not lidocaine (5µM) and their activity was stabilized for 15 min. Thereafter, they were subjected to local ischemia by ligation of the left anterior descending coronary artery for 20 min and reperfusion for 30 min. The coronary, aortic flows and severe arrhythmias (tachycardia and fibrillation) were monitored throughout perfusion. After the perfusion, mitochondria were extracted from the non-ischemic and ischemic zones and their respiration was evaluated. Results: The FO-rich diet triggered enrichment in n-3 PUFA of cardiac phospholipids. EPA, DPA and DHA were increased at the expense of AA and highest n-6 PUFAs. In the perfused hearts, pre-ischemic cardiac function was similar in the 4 subgroups. Ischemia reduced partially the coronary (-42% as soon as the 5th min of ischemia) and aortic (-64% at the end of ischemia) flows. The main disorders happened after ischemia with the occurrence of severe arrhythmias. Their severity was strongly increased in the FO group compared to the SSO group. Interestingly, lidocaine treatment suppressed completely their occurrence in the FO group without modifying them in the SSO group. Our data also show that the effects of lidocaine and PUFAs on reperfusion arrhythmias can be explained by changes in mitochondrial calcium retention capacities (mcrc). Conclusions: The pro-arrhythmic effect of n-3 PUFAs observed in our experimental conditions seems to be due to lower mcrc and maybe occurrence of calcium spikes. Lidocaine had the opposite effect. N-6 PUFA-rich hearts were resistant to lidocaine, since they had already reached their maximal mcrc in the absenc²e of the drug.