title: Activation of N-methyl-d-aspartate receptors reduces heart rate variability and facilitates atrial fibrillation in rats.
abstract: OBJECTIVE
  The goal of this study was to assess the effects of N-methyl-d-aspartate (NMDA) receptors activation on heart rate variability (HRV) and susceptibility to atrial fibrillation (AF).
  
  
  RESULTS
  Rats were randomized for treatment with saline, NMDA (agonist of NMDA receptors), or NMDA plus MK-801 (antagonist of NMDA receptors) for 2 weeks. Heart rate variability was evaluated by using implantable electrocardiogram telemeters. Atrial fibrillation susceptibility was assessed with programmed stimulation in isolated hearts. Compared with the controls, the NMDA-treated rats displayed a decrease in the standard deviation of normal RR intervals, the standard deviation of the average RR intervals, the mean of the 5-min standard deviations of RR intervals, the root mean square of successive differences, and high frequency (HF); and an increase in low frequency (LF) and LF/HF (all P< 0.01). Additionally, the NMDA-treated rats showed prolonged activation latency and reduced effective refractory period (all P< 0.01). Importantly, AF was induced in all NMDA-treated rats. While atrial fibrosis developed, connexin40 downgraded and metalloproteinase 9 upgraded in the NMDA-treated rats (all P< 0.01). Most of the above alterations were mitigated by co-administering with MK-801.
  
  
  CONCLUSIONS
  These results indicate that NMDA receptors activation reduces HRV and enhances AF inducibility, with cardiac autonomic imbalance, atrial fibrosis, and degradation of gap junction protein identified as potential mechanistic contributors.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, Hubei 430060, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, Hubei 430060, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.|Montreal Heart Institute, University of Montreal, Montreal, QC, Canada.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, Hubei 430060, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, Hubei 430060, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, Hubei 430060, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, Hubei 430060, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang District, Wuhan, Hubei 430060, China.|Cardiovascular Research Institute, Wuhan University, Wuhan, China.|Masonic Medical Research Laboratory, 2150 Bleecker Street, Utica, NY 13501, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
mesh_terms: D000200:Action Potentials; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D017630:Connexins / Q000378:metabolism; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005355:Fibrosis; D006329:Heart Conduction System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity*; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000378:metabolism; D013997:Time Factors; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D020780:Matrix Metalloproteinase 9; D016202:N-Methylaspartate; D016194:Receptors, N-Methyl-D-Aspartate; D000097003:Gap Junction alpha-5 Protein; C572337:Mmp9 protein, rat
keywords: Atrial fibrillation; Heart rate variability; N-Methyl-d-aspartate receptors