フレカイナイドの虚血心に及ぼす心筋保護効果

The effect of Flecainide on 2 hour occlusion-induced myocardial damages in dog

　フレカイナイドは，新しく開発された強力な抗不整脈薬であり^1），臨床的にも各種の不整脈に有効であるという報告が多くされている^2）。電気生理学的には，VaughanWilliamsの分類ではIc群に属し，Naチャンネルを抑制し，Vmaxを用量依存性に抑える反面，他のI群の薬剤と異なり，活動電位持続時間に影響を与えないとされている^3）。

　本剤はわが国では治験段階ではあるが，その半減期が比較的長いこと^4），その強力な抗不整脈のわりに毒性が低く^5），また，血行動態的にも，キシロカインと同様に陰性の変力作用および変時作用の影響は少なく^6），特に心機能の低下を伴うと予想される虚血時の不整脈にも使用しやすいなど，従来の抗不整脈剤に比較し使いやすい点より，本邦に導入されれば使用頻度が高くなると予想される。

This study was designed to clarify whether or not flecainide have cardioprotective effect on is-chemic myocardium. Nineteen dogs anesthetized and subjected to 2 h coronary occlusion, were di-vided into 2 groups. In the control group, physio-logical saline was infused, and in the flecainide group, 2 mg/kg of flecainide acetate and followed by 100 pg/kg/min continous infusion. To assess the cardioprotective effect, mitochondrial function and lysosomal enzyme activities were measured.Two hours after occlusion, mitochondria were pre-pared from both ischemic and non-ischemic areas in each group, and their function (respiratory control index, and the rate of oxygen consumption in state III respiration) were measured polarographically with succinate as substrate. Fractionation of myocardial tissue from both non-ischemic and ischemic areas was performed according to the method of Weglicki et al, and the activities of lysosomal enzymes (N-acetyl-β-glucosaminidase, and β-glucuronidase) were measured. In the control group, mitochondrial dys-function and leakage of lysosomal enzymes induced by 2 h occlusion were observed. On the contrary, administration of flecainide maintained significantly mitochondrial function, and prevented significantly leakage of lysosomal enzymes. These results in-decated that flecainide had cardioprotective effect as well as antiarrhythmic effects in ischemic myo-cardium.