Previous work has shown that nitric oxide production alters the relative height of the dicrotic notch (RHDN) in the peripheral arterial pulse of rabbits (Weinberg et al., 2001) and people (Chowienczyk et al., 1999), most likely through an influence on wave reflection. Preliminary evidence in both species shows that administration of glucose also alters notch height or augmentation index (AI), putatively because glucose stimulates the release of insulin which in turn stimulates the release of nitric oxide. This phenomenon could form the basis of a simple, non-invasive test of endothelial function. The work described in this thesis was designed to assess further the effect of glucose on arterial wavespeed (as a measure of stiffness), wave reflection and waveform. In the first study, an MR scanner was used to obtain brachial artery diameters and blood flow rates through the cardiac cycle in healthy volunteers before and after oral administration of glucose. In preliminary trials, MR images were processed in MATLAB® using different image analysis techniques; normalised cross correlation (NCC), a well-established method, was chosen for the automated acquisition of diameter and velocity waveforms. Pulse wave behaviour was then analysed using the diameter-velocity form of Wave Intensity Analysis (WIA) method, recently developed by Feng and Khir (2010). The study failed to show the expected effects of glucose. Furthermore, the diameter distentions detected for the brachial artery during the cardiac cycle appeared unphysiologically high and the calculated wave speeds appeared unphysiologically low. There were three possible sources of error: (1) the image analysis technique used to determine diameter waveforms, (2) the derivation of the new diameter-velocity form of WIA, and (3) the sugar hypothesis itself. The rest of the thesis describes investigations of these potential problems. To check the NCC-based image analysis methods, they were used in a study of aortic MR data that had previously been analysed by other methods (Li et al., 2010). Similar to the brachial artery/sugar experiment, non-physiological wavespeed values and high diameter distenstions were obtained, presumably due to an inaccuracy of the NCC image analysis technnique. Additionally, the wave behaviour in different aortic locations did not agree with well-established properties, presumably due to errors in the new WIA method. An attempt was made to find a consistent relation between NCC-derived diameters and manually-derived diameters, in order to develop a method for correcting the NCC data. However, no consistent relationship was found. This study provided additional evidence that the NCC method used in conjunction with noisy MRI data is unreliable. To assess the sugar-vasodilatation hypothesis, volume waveforms in the finger and pressure waveforms in the radial artery were measured by, respectively, photoplethysmography (PPG) and applanation tonometry, before and after the administration of a glucose or control drink to healthy volunteers. The radial pressure waveforms were used to calculate central aortic pressure waveforms, using the generalised transfer function described by Karamanoglu et al. (1993). Al, RHDN and the relative height of the diastolic peak (RHDP) of these waveforms were analysed. Despite the small sample size, a significant result was obtained for PPG RHDN, and borderline trends were obtained for other indices. Overall, the results were interpreted as supporting the hypothesis. Finally, the reliability of using the new diameter-velocity method of WIA was compared with the original pressure-velocity method in a polyurethane model of the aorta and its major branches. Pressure, velocity and diameter along the aorta to the femoral artery, and along arm vessels, were measured in the model and wave behaviour in the brachial artery and aorta was examined using both forms of WIA. Additionally, the aorta of the model was wrapped with tape or cling film in order to alter its compliance, an effect that was expected in the real circulation after the administration of glucose. Effects of aortic stiffening on wavespeed and wave intensity were observed in the aorta and arm arteries. However, the diameter-velocity form of WIA gave results that disagreed strongly with theoretical predictions. There may therefore be practically insupportable assumption in its derivation. In conclusion, it appears that both the NCC-MRI method and the diameter-velocity theory used in the initial brachial artery study may be unreliable. Some evidence was obtained for the hypothesised effect of sugar using other techniques.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:574052 |
| Date | January 2013 |
| Creators | Sardarlou, Mehdiye |
| Contributors | Weinberg, Peter ; Caro, Colin |
| Publisher | Imperial College London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/10044/1/11202 |
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