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Heart Rate Variability used to assess changing autonomic functionin Transmissible Spongiform Encephalopathies.

Glover, David

[Thesis]. Manchester, UK: The University of Manchester; 2011.

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Abstract

The dorsal vagal nucleus (DMNX) and nucleus ambiguus (NA) are two anatomicallydistinct regions of the medulla oblongata of the brainstem involved with the control ofthe heart on a beat to beat basis. The vagus nerve has parasympathetic cell bodieslocated in the DMNX and NA. The presence of the disease associated prion (PrPD) inthe DMNX and NA is used in the post mortem diagnosis of transmissible spongiformencephalopathies (TSEs) in animals. It has been shown that PrPD alters theneuronal discharge properties of infected tissue (Barrow, Holmgren et al.1999;Collinge, Whittington et al. 1994). I wished to investigate whether a change inheart rate variability (HRV) influenced by the presence of PrPD deposits in brainstemareas of animals and people incubating TSEs would be detectable.Recordings from control and infected sheep, cattle and humans, consisting of threehundred-second samples of electrocardiogram (ECG) were collected from speciesspecific healthy controls and subjects incubating TSE disease. Data were digitised ata sampling frequency of 1kHz and were translated and analysed using standardsoftware (CED Spike2 ; IBM SPSS). Artefacts and missed beats were correctedbased upon screening by eye. ECG R-wave timings were obtained in order todetermine variability in the R-R intervals. An instantaneous tachogram wasconstructed from which power spectra were calculated.Power spectral analysis along with simpler time domain estimates of HRV, such asRMSSD, were employed to investigate differences between control and infectedanimals. In addition R wave variability within each breath was utilized to examine thevagal control of the heart in relation to breathing and thus investigate a change infunction of the specific neurological areas of the brainstem used as diagnostic criteriafor 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. Repeatednon-invasive longitudinal tests may provide a means to screen animals and humansfor the presence of disease associated prions and may give applications in theobjective assessments of putative therapeutics in addition to identifying TSE diseaseat a preclinical stage.ReferencesBarrow, P. A., Holmgren, C. D., Tapper, A. J., & Jefferys, J. G. 1999, "Intrinsic physiologicaland morphological properties of principal cells of the hippocampus and neocortex in hamstersinfected with scrapie", Neurobiol.Dis., vol. 6, no. 5, pp. 406-423.Collinge, J., Whittington, M. A., Sidle, K. C., Smith, C. J., Palmer, M. S., Clarke, A. R., &Jefferys, J. G. 1994, "Prion protein is necessary for normal synaptic function", Nature, vol.370, no. 6487, pp. 295-297.