Mathematical modeling of blood-gas kinetics for the volatile organic compounds isoprene and acetone / by Julian King

• VerfasserIn: King, Julian
• Place / Publishing House: 2010
• Year of Publication: 2010
• Language: English
• Classification: 33.07 - Spektroskopie; 42.10 - Theoretische Biologie; 31.80 - Angewandte Mathematik; 42.11 - Biomathematik. Biokybernetik; 35.13 - Reaktionskinetik
• Physical Description: VI, 184, 2 S.; Ill., graph. Darst.
• Notes: Enth. u.a. 5 Veröff. d. Verf. aus den Jahren 2009 - 2010

ger: Breath gas analysis is based on the compelling concept that the exhaled breath levels of endogenously produced volatile organic compounds (VOCs) can provide a direct, non-invasive window to the blood and hence, by inference, to the body. In this sense, breath VOCs are regarded as a comprehensive repository of valuable physiological and clinical information, that might be exploited in such diverse areas as diagnostics, therapeutic monitoring or general dynamic assessments of metabolic function, pharmacodynamics (e.g., in drug testing) and environmental exposure (e.g., in occupational health). Despite this enormous potential, the lack of standardized breath sampling regimes as well as the poor mechanistic understanding of VOC exhalation kinetics could cast a cloud over the widespread use of breath gas analysis in the biomedical sciences. In this context, a primary goal of the present thesis is to provide a better quantitative insight into the breath behavior of two prototypic VOCs, isoprene and acetone. A compartmental modeling framework is developed and validated by virtue of real-time breath measurements of these trace gases during distinct physiological states. In particular, the influence of various hemodynamic and ventilatory parameters on VOC concentrations in exhaled breath is investigated. This approach also complements previous steady state investigations in toxicology. From a phenomenological point of view, both acetone and isoprene concentrations in end-tidal breath are demonstrated to exhibit a reproducible non-steady state behavior during moderate workload challenges on a stationary bicycle. However, these dynamics depart drastically from what is expected on the basis of classical pulmonary inert gas elimination theory. More specifically, the start of exercise is accompanied by an abrupt increase in breath isoprene levels, usually by a factor of 3 to 4 compared with the steady state value during rest. This phase is followed by a gradual decline and the development of a new steady state after about 15 min of pedaling.<br />Acetone concentrations closely resemble the profile of alveolar ventilation, resulting in slightly increased, roughly stable levels during the individual workload segments. While for acetone the above-mentioned discrepancy can be explained by reference to gas exchange mechanisms in the conductive airways, a major part of breath isoprene variability during exercise conditions can be attributed to an increased fractional perfusion of potential storage and production sites, leading to higher levels of mixed venous blood concentrations at the onset of physical activity. In this context, various lines of supportive evidence for an extrahepatic tissue source of isoprene are presented. The results discussed within the framework of this thesis are a first step towards new guidelines for the breath gas analysis of isoprene as well as acetone and are expected to have general relevance for quantitatively examining the exhalation, storage, transport, and biotransformation processes associated with volatile organic compounds in vivo.