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Endothelin-B receptors and ventricular arrhythmogenesis in the rat model of acute myocardial infarction

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Abstract

The arrhythmogenic effects of endothelin-1 (ET-1) are mediated via ETA-receptors, but the role of ETB-receptors is unclear. We examined the pathophysiologic role of ETB-receptors on ventricular tachyarrhythmias (VT/VF) during myocardial infarction (MI). MI was induced by coronary ligation in two animal groups, namely in wild-type (n = 63) and in ETB-receptor-deficient (n = 61) rats. Using a telemetry recorder, VT/VF episodes were evaluated during phase I (the 1st hour) and phase II (2–24 h) post-MI, with and without prior β-blockade. Action potential duration at 90% repolarization (APD90) was measured from monophasic epicardial recordings and indices of sympathetic activation were assessed using fast-Fourier analysis of heart rate variability. Serum epinephrine and norepinephrine were measured with radioimmunoassay. MI size was similar in the two groups. There was a marked temporal variation in VT/VF duration; during phase I, it was higher (p = 0.0087) in ETB-deficient (1,519 ± 421 s) than in wild-type (190 ± 34 s) rats, but tended (p = 0.086) to be lower in ETB-deficient (4.2 ± 2.0 s) than in wild-type (27.7 ± 8.0 s) rats during phase II. Overall, the severity of VT/VF was greater in ETB-deficient rats, evidenced by higher (p = 0.0058) mortality (72.0% vs. 32.1%). There was a temporal variation in heart rate and in the ratio of low- to high-frequency spectra, being higher (<0.001) during phase I, but lower (p < 0.05) during phase II in ETB-deficient rats. Likewise, 1 h post-MI, serum epinephrine (p = 0.025) and norepinephrine (p < 0.0001) were higher in ETB-deficient (4.20 ± 0.54, 14.24 ± 1.39 ng/ml) than in wild-type (2.30 ± 0.59, 5.26 ± 0.67 ng/ml) rats, respectively. After β-blockade, VT/VF episodes and mortality were similar in the two groups. The ETB-receptor decreases sympathetic activation and arrhythmogenesis during the early phase of MI, but these effects diminish during evolving MI.

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Acknowledgments

Agapi Vilaeti, MD, and Eleftheria Karambela, RN, assisted during the experiments. Eleni Goga, MSc, offered invaluable help as a research coordinator. This work was supported by the Cardiovascular Research Institute, Ioannina and Athens, Greece.

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Authors and Affiliations

  1. Department of Cardiology, University of Ioannina, 1 Stavrou Niarxou Avenue, 45110, Ioannina, Greece

    Dimitrios L. Oikonomidis, Giannis G. Baltogiannis, Alexandros T. Tzallas, Maria G. Agelaki, Aikaterini J. Megalou & Theofilos M. Kolettis

  2. Engineering Informatics and Telecommunications, University of Western Macedonia, Kozani, Greece

    Dimitrios G. Tsalikakis

  3. Department of Computer Sciences, University of Ioannina, Ioannina, Greece

    Alexandros T. Tzallas

  4. Department of Nuclear Medicine, University of Ioannina, Ioannina, Greece

    Xanthi Xourgia & Andreas Fotopoulos

  5. ELPEN Research Laboratory, Pikermi, Athens, Greece

    Apostolos Papalois

  6. Department of Cardiology, Athens Red Cross Hospital, Athens, Greece

    Zenon S. Kyriakides

  7. Cardiovascular Research Institute, Ioannina, Greece

    Apostolos Papalois, Zenon S. Kyriakides & Theofilos M. Kolettis

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  1. Dimitrios L. Oikonomidis
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  2. Dimitrios G. Tsalikakis
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  11. Theofilos M. Kolettis
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Correspondence to Theofilos M. Kolettis.

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Oikonomidis, D.L., Tsalikakis, D.G., Baltogiannis, G.G. et al. Endothelin-B receptors and ventricular arrhythmogenesis in the rat model of acute myocardial infarction. Basic Res Cardiol 105, 235–245 (2010). https://doi.org/10.1007/s00395-009-0066-7

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  • DOI: https://doi.org/10.1007/s00395-009-0066-7

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