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

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 (Mg(2+)), 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 Mg(2+) 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). Mg(2+) 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 Mg(2+) may contribute to HHcy-induced conduction abnormalities.

• Authors: Chirag V Soni, Suresh C Tyagi, Nathan D Todnem, Srikanth Givvimani, Sathnur B Pushpakumar, Juan Villafane, Claudio Maldonado
• Journal: Cell biochemistry and biophysics (Cell Biochem Biophys) Vol. 74 Issue 1 Pg. 59-65 (Mar 2016) ISSN: 1559-0283 [Electronic] United States
• PMID: 26972302 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cystathionine beta-Synthase
• Magnesium

Topics

• Action Potentials
• Animals
• Cystathionine beta-Synthase (genetics, metabolism)
• Hyperhomocysteinemia (metabolism, physiopathology)
• Magnesium (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Refractory Period, Electrophysiological
• Sinoatrial Node (metabolism, physiopathology)