| Cardioprotective effects of an active metabolite of furnidipine in 2 models of isolated heart and on in vivo ischemia–induced and reperfusion-induced arrhythmias in rats. | |
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MedLine Citation:
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PMID: 21052014 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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Tadeusz F Krzemiński; Katarzyna Mitrega; Benoy Varghese; Damian Hudziak; Maurycy Porc; Agnieszka Kedzia; Andrzej W Sielańczyk; Anna Jabłecka; Marek Jasiński |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 57 ISSN: 1533-4023 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-05-02 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 183-93 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Cardiovascular Research Division, Medical University of Silesia, ul. Jordana 19, 41-808 Zabrze, Poland. tadkrzem@ka.onet.pl |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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