Pentobarbital is the most suitable anesthetic offering stable hemodynamic values during arrhythmia studies. These hemodynamic values, which were similar to physiological values in awake rats, the long arrhythmia duration during reperfusion and approximately 50% mortality index are crucial parameters for evaluating antiarrhythmic drugs.

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Dihydropyridines are known not only to have antiarrhythmic effects but also to exert a significant cardiac depressive influence. We previously showed that M-2, an active and final metabolite of furnidipine, had cardioprotective effects without the marked cardiac depression seen with this dihydropyridine. We studied the influence of M-2 infusion (10(-7) M) on hemodynamics during low-flow and regional ischemia in the rat working heart. We examined the protection conferred by M-2 infusion (10(-7) M) against effects of veratridine-induced intracellular calcium overload in the Langendorff heart. Additionally, we performed an in vivo study to explore the effects of oral administration of M-2 at different times and doses, in the ischemia- and reperfusion-induced arrhythmias model. M-2 improved coronary flow during low-flow and regional ischemia while favorably maintaining aortic pressure parameters. M-2 provided outstanding protection against deleterious effects of calcium overloading by significantly preventing rise in left ventricular diastolic pressure and decrease in coronary flow. M-2 reduced mortality and incidence and duration of severe arrhythmias while exhibiting differential influence on blood pressure, which depended on dose and time of administration and could suggest its clinical indication. The results of our entire study establish a beneficial cardioprotective role of M-2, which exhibited pleiotropic effects on the ischemic heart by imparting protection in various ways. This combined with 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 cardioprotective drugs.

Safety and feasibility of CCB for AF in HF patients with CIED are comparable to subjects with structurally nor-mal heart; however, stable positioning of the balloon in the right inferior pulmonary vein may be more challenging. Although late recurrences are common, ablation reduces arrhythmia burden and leads to a long-term improvement of symptoms and echocardiographic indices.

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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 6-35 th 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.