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Chronic Istaroxime Improves Cardiac Function and Heart Rate Variability in Cardiomyopathic Hamsters

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Abstract

Purpose

Istaroxime is a new luso-inotropic compound. It exerts inotropic action by reducing Na+/K+-ATPase activity, and simultaneously it stimulates sarcoplasmic reticulum Ca2+-ATPase function, thus also inducing lusitropic action. The aim of present study is to assess the effect of chronic istaroxime treatment on cardiac function and heart rate variability in Bio TO.2 Syrian hamster model of progressive heart failure.

Methods

Bio TO.2 hamsters were daily treated, from 12 to 28 weeks of age, with 30 mg/kg/day oral istaroxime. Age-matched Bio TO.2 and Bio F1B hamsters were treated with vehicle and used as diseased and healthy controls. At the end of treatment, hearts function and autonomic cardiac control were evaluated.

Results

Hearts from vehicle-treated Bio TO.2 when compared with hearts from Bio F1B showed higher heart/body weight ratio, and lower left ventricular systolic pressure (LVSP), positive and negative derivative of LV pressure (dP/dT), coronary flow rate (CFR). Hearts from istaroxime-treated when compared with those of vehicle-treated hamsters, showed the reduction of heart/body weight ratio, and the increase of LVSP, of both positive and negative dP/dT, and of CFR. Autonomic cardiac control, evaluated by HRV analysis, indicated in vehicle-treated Bio TO.2 hamsters, when compared to healthy, a shift towards increased sympathetic and decreased parasympathetic activities. Istaroxime-treatment preserved parasympathetic activity.

Conclusions

Chronic istaroxime improves cardiac function and heart rate variability in Bio TO.2 Syrian hamster model of progressive heart failure.

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Acknowledgements

We gratefully acknowledge the technical assistance from Giuseppina Magni and Augusta Bellucci

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Authors and Affiliations

  1. Research and Development, Pharmacology Department, Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., Via Pontina km 30.400, 00040, Pomezia, Rome, Italy

    Pietro Lo Giudice, Giovan Giuseppe Mattera & Franco Borsini

  2. University of Montpellier 1 and CNRS UMR5232, Montpellier, France

    Jean-Pierre Gagnol

Authors
  1. Pietro Lo Giudice
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  2. Giovan Giuseppe Mattera
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  3. Jean-Pierre Gagnol
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  4. Franco Borsini
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Correspondence to Pietro Lo Giudice.

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Lo Giudice, P., Mattera, G.G., Gagnol, JP. et al. Chronic Istaroxime Improves Cardiac Function and Heart Rate Variability in Cardiomyopathic Hamsters. Cardiovasc Drugs Ther 25, 133–138 (2011). https://doi.org/10.1007/s10557-011-6283-y

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  • DOI: https://doi.org/10.1007/s10557-011-6283-y

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