Abstract
Rhythms characterise the physiology of all living things, and rhythmic patterns can be observed in almost all aspects of daily human life. Disruption of rhythms is linked to poor health and may be caused by disease, or desynchrony between activity, behaviour, and internal time cues. Since rhythms are individual and dynamic, single time point assessment provides limited information and is potentially misleading. On the other hand, capturing dynamic information is traditionally difficult and invasive. In this thesis I investigated how these difficulties could be overcome using a novel, prototype portable microdialysis sampling device, U-RHYTHM.
I have shown that U-RHYTHM is a safe, reliable method and well-tolerated by participants. In a series of small proof-of-principle studies using healthy volunteers, the U-RHYTHM device and abdominal subcutaneous microdialysis, diurnal and ultradian rhythms of 8 adrenal steroids were shown and validated against plasma, 7 of which have never previously been described in tissue. Next, using a targeted metabolomics approach, multiple tissue metabolites were found, showing daily- and food-driven rhythms. Finally, in ambulatory studies, the novel detection of tissue melatonin rhythms simultaneously with cortisol and cortisone was achieved and presented alongside rhythmic data from other non-invasive wearable devices. Across all studies, limitations on the technique related to the recovery of some lipophilic, hydrophobic compounds.
These studies show that U-RHYTHM can be used to investigate daily trends, ultradian details, and interactions between rhythmic processes. Data from U-RHYTHM studies could lead to new methods for diagnosis of endocrine and metabolic conditions, and to the increased understanding how lifestyle-related rhythm disruption leads to poor health outcomes. The unintrusive nature of the technique provides the flexibility to investigate in both free living and controlled conditions. Further work is needed to validate findings in a larger population.