title: Subcutaneous nerve activity and mechanisms of sudden death in a rat model of chronic kidney disease.
abstract: The mechanisms of sudden death in chronic kidney disease (CKD) remain unclear.
  
  
  
  The purpose of this study was to test the hypotheses that subcutaneous nerve activity (SCNA) can be used to estimate sympathetic tone in ambulatory rats and that abrupt reduction of SCNA precedes the spontaneous arrhythmic death of Cy/+ rats.
  
  
  
  Radiotransmitters were implanted in ambulatory normal (N = 6) and Cy/+ (CKD; N = 6) rats to record electrocardiogram and SCNA. Two additional rats were studied before and after chemical sympathectomy with 6-hydroxydopamine.
  
  
  
  In normal rats, the baseline heart rate (HR) and SCNA were 351 ± 29 bpm and 5.12 ± 2.97 mV·s, respectively. SCNA abruptly increased HR by 4.31% (95% confidence interval 4.15%-4.47%). In comparison, the CKD rats had reduced baseline HR (336 ± 21 bpm, P < .01) and SCNA (4.27 ± 3.19 mV·s, P < .01). When SCNA was observed, HR increased by only 2.48% (confidence interval 2.29%-2.67%, P < .01). All Cy/+ rats died suddenly, preceded by sinus bradycardia, advanced (second- and third-degree) AV block (N = 6), and/or ventricular tachycardia or fibrillation (N = 3). Sudden death was preceded by a further reduction of SCNA (3.22 ± 2.86 mV·s, P < .01) and sinus bradycardia (243 ± 55 bpm, P < .01). Histologic studies in CKD rats showed myocardial calcification that involved the conduction system. Chemical sympathectomy resulted in progressive reduction of SCNA over 7 days.
  
  
  
  SCNA can be used to estimate sympathetic tone in ambulatory rats. CKD is associated with reduced HR response to SCNA and conduction system diseases. Abrupt reduction of sympathetic tone precedes AV block, ventricular arrhythmia, and sudden death of CKD rats.
authors.affiliation: Krannert Institute of Cardiology, Division of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiac Surgery, First Affiliated Hospital of China Medical University, Shengyang, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Neal X
authors.initials: NX
authors.lastname: Chen
authors.affiliation: Krannert Institute of Cardiology, Division of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Shirazi
authors.affiliation: Department of Biostatistics, Indiana University School of Medicine and the Fairbanks School of Public Health, Indianapolis, Indiana.
authors.forename: Changyu
authors.initials: C
authors.lastname: Shen
authors.affiliation: Krannert Institute of Cardiology, Division of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana; Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan.
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fishbein
authors.affiliation: Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, Indiana.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.affiliation: Krannert Institute of Cardiology, Division of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: chenpp@iu.edu.
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D016757:Death, Sudden, Cardiac / Q000209:etiology* / Q000517:prevention & control; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000379:methods; D006339:Heart Rate / Q000502:physiology; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000503:physiopathology; D013233:Stellate Ganglion / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*
keywords: Atrioventricular block; Chronic kidney disease; Subcutaneous nerve activity; Sudden death