title: 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.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, 40202, USA. cvsoni01@louisville.edu.
authors.forename: Chirag V
authors.initials: CV
authors.lastname: Soni
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Todnem
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Givvimani
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
authors.forename: Sathnur B
authors.initials: SB
authors.lastname: Pushpakumar
authors.affiliation: Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY, 40506, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Villafane
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, KY, 40202, USA.|Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Maldonado
mesh_terms: D000200:Action Potentials; D000818:Animals; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000378:metabolism / Q000503:physiopathology*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012032:Refractory Period, Electrophysiological; D012849:Sinoatrial Node / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D003541:Cystathionine beta-Synthase; D008274:Magnesium
keywords: Arrhythmia; Atrioventricular node; Cardiac N-methyl-D-aspartate receptor; Electrophysiological studies; Homocysteine; Sinoatrial node; Sudden cardiac death