Differential Effects of Furnidipines' Metabolites on Reperfusion-Induced Arrhythmias in Rats In Vivo

被引:2
作者
Mitrega, Katarzyna A. [1 ]
Porc, Maurycy [1 ]
Krzeminski, Tadeusz F. [1 ]
机构
[1] Med Univ Silesia, Chair & Dept Pharmacol, Katowice, Poland
来源
PLOS ONE | 2014年 / 9卷 / 02期
关键词
ISCHEMIA; CHANNEL; NIFEDIPINE; DERIVATIVES; MODEL;
D O I
10.1371/journal.pone.0089477
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:6
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