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.