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

Abstract

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.

Cardiomyopathy development protection after myocardial infarction in rats: Successful competition for major dihydropyridines’ common metabolite against captopril

“…Since it was clarified, M-2 is also a common metabolite present in degradation pathways of many widely used dihydropyridines (including nifedipine), outcomes of our investigations with this agent supply new outlook not only on the effects of M-2 itself, but on this whole group of drugs as well [ 31 – 34 ]. Our former research with M-2 conducted on various experimental in vivo and ex vivo rat models established its beneficial effects on mortality [ 31 , 34 ], ischemia- and reperfusion-induced lethal arrhythmias [ 31 , 33 – 34 ] as well as hemodynamic parameters (e.g. blood pressure or coronary flow) [ 33 – 34 ].…”

“…Our former research with M-2 conducted on various experimental in vivo and ex vivo rat models established its beneficial effects on mortality [ 31 , 34 ], ischemia- and reperfusion-induced lethal arrhythmias [ 31 , 33 – 34 ] as well as hemodynamic parameters (e.g. blood pressure or coronary flow) [ 33 – 34 ].…”

Dihydropyridines’ metabolites-induced early apoptosis after myocardial infarction in rats; new outlook on preclinical study with M-2 and M-3

“…The biochemical findings in blood at 4th day after myocardial infarction showed that only the M-3 pretreatment reduced significantly GOT concentration in comparison to control as well as it strongly reduced CK values in comparison to M-2 and DMSO groups ( p < 0.05). Although some beneficial effects of the tested compounds were present, in view of our previous experiments with these agents [ 34 , 35 , 38 , 57 ] it could be concluded that the model used in present study is not suitable to quantify their optimal cardioprotective effects.…”

“…In general, the balance between programmed cell death and regeneration processes in all kinds of tissues seems to be crucial aspect in determination of myocardium recovery after infarction. In the light of the histological results presented above, M-2 shows itself as more attractive agent for oral pretreatment in early stages of ischemia by non-stable individuals suggested elsewhere [ 57 ] due to its more specific action in stimulation resorptive processes in granulation tissue as well as in arteriolar walls. Furthermore, this working hypothesis enlarge our outcomes from previous study where M-2 positively influenced on post-infarction heart remodeling.…”