Clinical & Experimental Cardiology
Open Access

Abstract

The Beneficial Effects of Post-myocardial Infarction, Long Oral Treatment with M-2 in Preventing the Development of Cardiomyopathy in Rats

Katarzyna A Mitręga, Jerzy K Nożyński, Maurycy Porc and Tadeusz F Krzemiński

We have previously shown that the furnidipines’ metabolite M-2 improved coronary flow during low-flow and regional ischemia in vitro. This resulted in reduced mortality and incidence, or duration, of severe arrhythmias in in vivo models.

The aim of this study was to establish the optimal period of oral treatment with M-2 for preventing or delaying the post-myocardial infarction (MI) cardiomyopathy development in rats.

The male Sprague-Dawley rats (n=120) were used to model the experimental MI in vivo and also to model physiological perfusion of the isolated rat heart. The MI was invoked by permanent left coronary artery occlusion. The surviving rats were treated with M2 (4 mg/kg daily) administered from 21^st-28^th, 21^st-35^th, 11-28^th, 11-35^th or from 6-35th day, post MI, for the routine estimation of morphological features of cardiomyopathy.

We summarized that the major vectors of the effects of treatment with M-2 were:

1) “Revitalisation” of the vessels and infarct scars.

2) Intensification of angiogenic events.

3) Inhibition of cardiomyopathic re-modeling of the myocardial tissue as a consequence of two mentioned above processes.

Rats treated with M-2 for the longest periods had complete protection from developing cardiomyopathy.

The early beginning and long treatment with M-2 was found the most effective for inhibiting the cardiomyopathic development. The good tolerance, long duration of action, low toxicity and relatively large therapeutic window, makes M-2, a promising candidate as a precursor for a new chemical class of cardio-protective drugs.