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Hyperhomocysteinemia Alters Sinoatrial and Atrioventricular Nodal Function: Role of Magnesium in Attenuating These Effects

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Abstract

Patients with hyperhomocysteinemia (HHcy), or elevated plasma homocysteine (Hcy), are at higher risk of developing arrhythmias and sudden cardiac death; however, the mechanisms are unknown. In this study, the effects of HHcy on sinus node function, atrioventricular conduction, and ventricular vulnerability were investigated by electrophysiological (EP) analysis, and the role of magnesium (Mg2+), an endogenous N-methyl-d-aspartate (NMDA) receptor antagonist, in attenuating EP changes due to HHcy was explored. Wild-type mice (WT) and mice receiving Hcy in the drinking water for 12 weeks (DW) were subjected to electrocardiographic and EP studies. DW compared to WT had significantly shorter RR, PR, QT, and HV intervals, corrected sinus node recovery times (CSNRT), Wenckebach periodicity (WP), atrioventricular nodal effective refractory periods (AVNERP), and right ventricular effective refractory periods (RVERP). To examine the role of Mg2+ in mitigating conduction changes in HHcy, WT, DW, and heterozygous cystathionine-β-synthase knockout mice (CBS +/−) were subjected to repeat EP studies before and after administration of low-dose magnesium sulfate (20 mg/kg). Mg2+ had no effect on EP variables in WT, but significantly slowed CSNRT, WP, and AVNERP in DW, as well as WP and AVNERP in CBS +/−. These findings suggest that ionic channels modulated by Mg2+ may contribute to HHcy-induced conduction abnormalities.

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Acknowledgments

This work was supported in part by National Institutes of Health Grants HL-88012, HL-74185, and HL-71010.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, 40202, USA

    Chirag V. Soni, Suresh C. Tyagi, Nathan D. Todnem, Srikanth Givvimani, Sathnur B. Pushpakumar & Claudio Maldonado

  2. Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA

    Claudio Maldonado

  3. Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY, 40506, USA

    Juan Villafane

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  1. Chirag V. Soni
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  2. Suresh C. Tyagi
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  3. Nathan D. Todnem
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  4. Srikanth Givvimani
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  7. Claudio Maldonado
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Correspondence to Chirag V. Soni.

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Soni, C.V., Tyagi, S.C., Todnem, N.D. et al. Hyperhomocysteinemia Alters Sinoatrial and Atrioventricular Nodal Function: Role of Magnesium in Attenuating These Effects. Cell Biochem Biophys 74, 59–65 (2016). https://doi.org/10.1007/s12013-015-0711-8

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  • DOI: https://doi.org/10.1007/s12013-015-0711-8

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