Mitrega Katarzyna A, Porc Maurycy, Krzeminski Tadeusz F
Chair and Department of Pharmacology, Medical University of Silesia, Katowice, Poland.
PLoS One. 2014 Feb 28;9(2):e89477. doi: 10.1371/journal.pone.0089477. eCollection 2014.
We previously established that furnidipine (FUR) and oxy dihydropyridines prevent rats mortality by strong reduction of the lethal arrhythmias in reperfusion. Therefore we decided to study the influence of three main metabolites (M-2, M-3, M-8) of FUR on ischemia-and reperfusion- induced arrhythmias and hemodynamic parameters in rat model to examine their independent activity. The metabolites (M-2, M-3, M-8) were given orally 20 mg/kg (24 and 1 h before ischemia). Mortality was significantly diminished in M-2 and M-3 treated groups with M-3 preventing animal mortality entirely. All three examined substances significantly reduced the duration and incidence of ventricular fibrillation (VF) with M-3, once again, completely preventing VF. Moreover, only M-3 significantly decreased the duration of ventricular tachycardia but had no influence on their incidence. Through the occlusion and reperfusion periods, M-2 and M-3 were markedly less hypotensive than M-8 and did not influence on heart rate. We conclude that two tested metabolites of FUR, M-3 and M-2 exhibited the most pronounced anti-arrhythmic effect being at the same time the most normotensive and therefore caused the most beneficial effects.
我们之前已经证实，福尼地平（FUR）和氧化二氢吡啶可通过大幅减少再灌注时的致死性心律失常来防止大鼠死亡。因此，我们决定研究FUR的三种主要代谢物（M-2、M-3、M-8）对大鼠模型中缺血和再灌注诱导的心律失常及血流动力学参数的影响，以检验它们的独立活性。代谢物（M-2、M-3、M-8）以20mg/kg的剂量口服给药（在缺血前24小时和1小时）。M-2和M-3治疗组的死亡率显著降低，其中M-3完全防止了动物死亡。所有三种受试物质均显著缩短了室颤（VF）的持续时间并降低了其发生率，M-3再次完全防止了VF。此外，只有M-3显著缩短了室性心动过速的持续时间，但对其发生率没有影响。在闭塞和再灌注期间，M-2和M-3的降压作用明显小于M-8，且对心率没有影响。我们得出结论，FUR的两种受试代谢物M-3和M-2表现出最显著的抗心律失常作用，同时也是最具血压正常化作用的，因此产生了最有益的效果。
