title: A novel quantitative method for diabetic cardiac autonomic neuropathy assessment in type 1 diabetic mice.
abstract: In this work, we used a sensitive and noninvasive computational method to assess diabetic cardiovascular autonomic neuropathy (DCAN) from pulse oximeter (photoplethysmographic; PPG) recordings from mice. The method, which could be easily applied to humans, is based on principal dynamic mode (PDM) analysis of heart rate variability (HRV). Unlike the power spectral density, PDM has been shown to be able to separately identify the activities of the parasympathetic and sympathetic nervous systems without pharmacological intervention. HRV parameters were measured by processing PPG signals from conscious 1.5- to 5-month-old C57/BL6 control mice and in Akita mice, a model of insulin-dependent type 1 diabetes, and compared with the gold-standard Western blot and immunohistochemical analyses. The PDM results indicate significant cardiac autonomic impairment in the diabetic mice in comparison to the controls. When tail-cuff PPG recordings were collected and analyzed starting from 1.5 months of age in both C57/Bl6 controls and Akita mice, onset of DCAN was seen at 3 months in the Akita mice, which persisted up to the termination of the recording at 5 months. Western blot and immunohistochemical analyses also showed a reduction in nerve density in Akita mice at 3 and 4 months as compared to the control mice, thus, corroborating our PDM data analysis of HRV records. Western blot analysis of autonomic nerve proteins corroborated the PPG-based HRV analysis via the PDM approach. In contrast, traditional HRV analysis (based on either the power spectral density or time-domain measures) failed to detect the nerve rarefaction.
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA kichon@wpi.edu.
authors.forename: Ki H
authors.initials: KH
authors.lastname: Chon
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: Bufan
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: Hugo F
authors.initials: HF
authors.lastname: Posada-Quintero
authors.affiliation: Department of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Kin L
authors.initials: KL
authors.lastname: Siu
authors.affiliation: Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
authors.forename: Marsha
authors.initials: M
authors.lastname: Rolle
authors.affiliation: Department of Physiology & Biophysics, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Brink
authors.affiliation: Department of Physiology & Biophysics, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Aija
authors.initials: A
authors.lastname: Birzgalis
authors.affiliation: Department of Physiology & Biophysics, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Leon C
authors.initials: LC
authors.lastname: Moore
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis* / Q000209:etiology; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003929:Diabetic Neuropathies / Q000175:diagnosis*; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010092:Oximetry / Q000379:methods*
keywords: autonomic nervous system; diabetic cardiac autonomic neuropathy; heart rate variability; photoplethysmogram; power spectral density; principal dynamic modes
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