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Reverse chamber remodelling following adrenergic-induced advanced cardiac dilatation and pump dysfunction

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Abstract

As adrenergic-induced cardiac dilatation is associated with cardiomyocyte cell death, whether cessation of excessive adrenergic effects can achieve complete reverse chamber remodelling in established cardiac dilatation and pump dysfunction has been questioned. We assessed whether following the development of cardiac dilatation and pump dysfunction subsequent to 6 months of daily β-adrenergic receptor agonist administration (isoproterenol [ISO] at 0.01 mg/kg daily) to rats, withdrawal of ISO administration for a further 4 months (ISO + recovery) reverses the adverse effects on the heart. Chronic ISO administration and the withdrawal of ISO administration were associated with changes in cardiomyocyte apoptosis, but not myocardial necrosis (pathological score). After 6 months of ISO administration, left ventricular (LV) end diastolic and systolic diameters, and the volume intercept of the LV diastolic pressure–volume relationship (LV V 0), were markedly increased and LV endocardial fractional shortening (FSend), LV end systolic chamber (slope of the systolic pressure–volume relationship-Ees) and myocardial (slope of the systolic stress–strain relationship-En) contractility were substantially decreased. Chronic ISO administration produced a 2.5 times increase in LV V 0 (ISO = 0.40 ± 0.04 vs. saline = 0.16 ± 0.01, P < 0.001). Following a 6-month period of ISO administration and a subsequent withdrawal period for a further 4 months, LV chamber diameters, LV V 0 (ISO + recovery = 0.21 ± 0.02 vs. saline = 0.23 ± 0.02, P < 0.001), FSend, LV Ees and LV En were all noted to be similar to control rats. The proportion of ISO + recovery rats with LV chamber diameters, LV V 0, FSend, LV Ees and LV En values above or below the 95% confidence interval for the saline + recovery rats was similar to the proportion of saline + recovery rats above or below their own 95% confidence intervals. In conclusion, even in the presence of adrenergic-induced cardiomyocyte apoptosis, marked cardiac dilatation and pump dysfunction produced by chronic β-adrenergic receptor activation can be completely reversed by withdrawal of the excessive adrenergic stimulus.

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Acknowledgments

This work was supported by the University Research Council of the University of the Witwatersrand, and the South African National Research Foundation.

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Authors and Affiliations

  1. Cardiovascular Pathophysiology and Genomics Research Unit, Faculty of Health Sciences, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, Johannesburg, 2193, South Africa

    Hendrik L. Booysen, Gavin R. Norton & Angela J. Woodiwiss

  2. Department of Medicine, Faculty of Health Sciences, Hatter Cardiovascular Research Institute, University of Cape Town, Observatory, Cape Town, South Africa

    Lionel H. Opie

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  1. Hendrik L. Booysen
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  2. Gavin R. Norton
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  3. Lionel H. Opie
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Correspondence to Angela J. Woodiwiss.

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Booysen, H.L., Norton, G.R., Opie, L.H. et al. Reverse chamber remodelling following adrenergic-induced advanced cardiac dilatation and pump dysfunction. Basic Res Cardiol 107, 238 (2012). https://doi.org/10.1007/s00395-011-0238-0

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  • DOI: https://doi.org/10.1007/s00395-011-0238-0

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