Subcutaneous nerve activity and mechanisms of sudden death in a rat model of chronic kidney disease

Ye Zhao, Xuening (Neal) Chen, Jonathan T. Shirazi, Changyu Shen, Shien-Fong Lin, Michael C. Fishbein, Sharon Moe, Peng-Sheng Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: The mechanisms of sudden death in chronic kidney disease (CKD) remain unclear. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
JournalHeart Rhythm
DOIs
StateAccepted/In press - 2016

Fingerprint

Sudden Death
Chronic Renal Insufficiency
Heart Rate
Chemical Sympathectomy
Atrioventricular Block
Bradycardia
Confidence Intervals
Oxidopamine
Neural Conduction
Ventricular Fibrillation
Ventricular Tachycardia
Cardiac Arrhythmias
Electrocardiography

Keywords

  • Atrioventricular block
  • Chronic kidney disease
  • Subcutaneous nerve activity
  • Sudden death

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Subcutaneous nerve activity and mechanisms of sudden death in a rat model of chronic kidney disease. / Zhao, Ye; Chen, Xuening (Neal); Shirazi, Jonathan T.; Shen, Changyu; Lin, Shien-Fong; Fishbein, Michael C.; Moe, Sharon; Chen, Peng-Sheng.

In: Heart Rhythm, 2016.

Research output: Contribution to journalArticle

@article{dd01d90a7ef14545813fb2c5364d9844,
title = "Subcutaneous nerve activity and mechanisms of sudden death in a rat model of chronic kidney disease",
abstract = "Background: The mechanisms of sudden death in chronic kidney disease (CKD) remain unclear. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.",
keywords = "Atrioventricular block, Chronic kidney disease, Subcutaneous nerve activity, Sudden death",
author = "Ye Zhao and Chen, {Xuening (Neal)} and Shirazi, {Jonathan T.} and Changyu Shen and Shien-Fong Lin and Fishbein, {Michael C.} and Sharon Moe and Peng-Sheng Chen",
year = "2016",
doi = "10.1016/j.hrthm.2015.12.040",
language = "English (US)",
journal = "Heart Rhythm",
issn = "1547-5271",
publisher = "Elsevier",

}

TY - JOUR

T1 - Subcutaneous nerve activity and mechanisms of sudden death in a rat model of chronic kidney disease

AU - Zhao, Ye

AU - Chen, Xuening (Neal)

AU - Shirazi, Jonathan T.

AU - Shen, Changyu

AU - Lin, Shien-Fong

AU - Fishbein, Michael C.

AU - Moe, Sharon

AU - Chen, Peng-Sheng

PY - 2016

Y1 - 2016

N2 - Background: The mechanisms of sudden death in chronic kidney disease (CKD) remain unclear. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

AB - Background: The mechanisms of sudden death in chronic kidney disease (CKD) remain unclear. Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

KW - Atrioventricular block

KW - Chronic kidney disease

KW - Subcutaneous nerve activity

KW - Sudden death

UR - http://www.scopus.com/inward/record.url?scp=84959462280&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959462280&partnerID=8YFLogxK

U2 - 10.1016/j.hrthm.2015.12.040

DO - 10.1016/j.hrthm.2015.12.040

M3 - Article

JO - Heart Rhythm

JF - Heart Rhythm

SN - 1547-5271

ER -