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Title: Heart rate variability used to assess changing autonomic functionin transmissible spongiform encephalopathies
Author: Glover, David
ISNI:       0000 0004 2708 3336
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2011
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The dorsal vagal nucleus (DMNX) and nucleus ambiguus (NA) are two anatomically distinct regions of the medulla oblongata of the brainstem involved with the control of the heart on a beat to beat basis. The vagus nerve has parasympathetic cell bodies located in the DMNX and NA. The presence of the disease associated prion (PrPD) in the DMNX and NA is used in the post mortem diagnosis of transmissible spongiform encephalopathies (TSEs) in animals. It has been shown that PrPD alters the neuronal discharge properties of infected tissue (Barrow, Holmgren et al.1999; Collinge, Whittington et al. 1994). I wished to investigate whether a change in heart rate variability (HRV) influenced by the presence of PrPD deposits in brainstem areas of animals and people incubating TSEs would be detectable. Recordings from control and infected sheep, cattle and humans, consisting of three hundred-second samples of electrocardiogram (ECG) were collected from species specific healthy controls and subjects incubating TSE disease. Data were digitised at a sampling frequency of 1kHz and were translated and analysed using standard software (CED Spike2 ; IBM SPSS). Artefacts and missed beats were corrected based upon screening by eye. ECG R-wave timings were obtained in order to determine variability in the R-R intervals. An instantaneous tachogram was constructed from which power spectra were calculated. Power spectral analysis along with simpler time domain estimates of HRV, such as RMSSD, were employed to investigate differences between control and infected animals. In addition R wave variability within each breath was utilized to examine the vagal control of the heart in relation to breathing and thus investigate a change in function of the specific neurological areas of the brainstem used as diagnostic criteria for such diseases. It was found there were significant differences (p<0.05) in the HRV of infected sheep, cattle and humans incubating TSE disease compared to control samples. Repeated non-invasive longitudinal tests may provide a means to screen animals and humans for the presence of disease associated prions and may give applications in the objective assessments of putative therapeutics in addition to identifying TSE disease at a preclinical stage.
Supervisor: Eisner, David Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: prion ; heart rate variability ; vCJD ; BSE ; scrapie