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

Katarzyna A Mitrega,Tadeusz F Krzeminski,Maurycy Porc,Anindita Das

doi:10.1371/journal.pone.0089477

Katarzyna A Mitrega, Tadeusz F Krzeminski + Show 2 more

Open Access

https://doi.org/10.1371/journal.pone.0089477

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Journal: PLoS ONE	Publication Date: Feb 28, 2014
Citations: 29	License type: CC BY 4.0

Affiliation: Medical University of Silesia

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.

Highlights

We previously established that furnidipine (FUR) and oxy dihydropyridines prevent rats mortality by strong reduction of the lethal arrhythmias in reperfusion
In previous study conducted by us, we noted that FUR and NIF given orally and i.v. had comparable anti-arrhythmic effects [6]
The anti-arrhythmic action of NIF after its i.v. administration was confirmed in experiments conducted by others [26,27]

Summary

Introduction

We previously established that furnidipine (FUR) and oxy dihydropyridines prevent rats mortality by strong reduction of the lethal arrhythmias in reperfusion. 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. 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. Only M-3 significantly decreased the duration of ventricular tachycardia but had no influence on their incidence. 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 caused the most beneficial effects.

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Conclusion