Nonlinear Dynamics of Microcirculation and Energy Metabolism for the Prediction of Cardiovascular Risk

The peripheral skin microcirculation reflects the overall health status of the cardiovascular system and can be examined non-invasively by laser methods to assess early cardiovascular disease (CVD) risk factors, i.e. oxidative stress and endothelial dysfunction. Examples of methods used for this task are the laser Doppler flowmetry (LDF) and laser fluorescence spectroscopy (LFS), which respectively allow tracing blood flow and the amounts of the coenzyme NAD(P)H (nicotamide adenine dinucleotide) that is involved in the cellular production of ATP (adenosine triphosphate) energy. In this work, these methods were combined with iontophoresis and PORH (post-occlusive reactive hyperaemia) reactive tests to assess skin microvascular function and oxidative stress in mice and human subjects. The main focus of the research was exploring the nonlinear dynamics of skin LDF and NAD(P)H time series by processing the signals with the wavelet transform analysis. The study of nonlinear fluctuations of the microcirculation and cell energy metabolism allows detecting dynamic oscillators reflecting the activity of microvascular factors (i.e. endothelial cells, smooth muscle cells, sympathetic nerves) and specific patterns of mitochondrial or glycolytic ATP production. Monitoring these dynamic factors is powerful for the prediction of general vascular/metabolic health conditions, and can help the study of the mechanisms at the basis of the rhythmic fluctuations of micro-vessels diameter (vasomotion). In this thesis, the microvascular and metabolic dynamic biomarkers were characterised <i>in-vivo</i> in a mouse model affected by oxidative stress and a human cohort of smokers. Data comparison, respectively, with results from control mice and non-smokers, revealed significant differences suggesting the eligibility of these markers as predictors of risk associated with oxidative stress and smoke. Moreover, a relevant link between microvascular and metabolic oscillators was observed during vasomotion induced by α-adrenergic (in mice) or PORH (in humans) stimulations, suggesting a possible role of cellular Ca²⁺oscillations of metabolic origin as drivers of vasomotion which is a theory poorly explored in literature. As future perspective, further exploration of these promising nonlinear biomarkers is required in the presence of risk factors different from smoke or oxidative stress and during vasomotion induced by stimuli different from PORH or α-adrenergic reactive challenges, to obtain a full picture on the use of these factors as predictors of risk and their role in the regulation of vasomotion.

Name dc:type.qualificationname

Doctor of Philosophy

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

University of Dundee

Year dc:date.issued

2018

Author dc:creator

• Smirni, Salvatore

Advisors dc:contributor.advisor

• Khan, Faisel
• MacDonald, Michael

• Skin microcirculation
• Energy metabolism
• Nonlinear dynamics
• Continuous wavelet transform
• Vasomotion
• Metabolic oscillations
• Microvascular oscillations
• Attractors
• Cardiovascular disease risk
• Oxidative stress
• Endothelial Dysfunction
• Biomedical Optics
• Biophotonics
• Bioenergetics
• Nonlinear phenomena
• Biophysics
• Physiology
• Blood flow
• Fluorescence Spectroscopy
• Laser Doppler Flowmetry

Language dc:language

eng

Identifier

oai:discovery.dundee.ac.uk:studenttheses/c551cbef-6f00-48ef-b753-ad76ac93daf4

OAI identifier oai:identifier

oai:discovery.dundee.ac.uk:studenttheses/c551cbef-6f00-48ef-b753-ad76ac93daf4