Respirent gases

The required data generally are obtained by administering a measured dose of the candidate compound -- often isotopically labelled -- to the rat or mouse either by injection or per os. The animal is housed in a glass metabolism "cage" where it receives food, water, and clean air, and its urine, feces, and respired gases are collected and examined for the parent chemical and its metabolites. Eventual postmortem tissue analysis and calculation of material balance complete the measurements necessary to satisfy the above purposes of metabolism and pharmacokinetic experiments. While in vitro biochemical studies are important adjuncts, it is also apparent that only experiments with intact, healthy, living animals will suffice to meet EPA criteria. 

Metabolite collection. Whereas the separation and collection of urine, feces, and respired gases is a simple matter with rodents, the quantitative isolation of microgram amounts of complex metabolites from large volumes of aqueous medium — especially seawater — has posed a major hurdle to studies in aquatic organisms. 

Table I. Excretion of radioactivity via respiration gases, urine, and feces by rats treated with a single oral dose of C-phosfolan.

All biochemical reactions are enzyme-mediated. The rate of an enzyme reaction depends on the substrate concentration at the location of the enzyme and thereby on the diffusion rate of a substrate to the enzyme. It is therefore important to permanently obtain an intimate contact between a cell or enzyme and substrate molecules. Additionally, the product generated in the bioreactor has to be extracted because it may under certain conditions inhibit its own production. In some processes there may also be even a prepurification in the bioreactor itself. If living micro-organisms have to be applied, it is necessary to provide sufficient nutrition and respiration gases in case of aerobic fermentation. All other reaction parameters such as temperature, pH-value and reaction time have to be controlled precisely. In many cases (generally with modem processes) the maintenance of microbiological integrity (sterile process) is absolutely mandatory for a successful fermentation. 

The analysis of the gas mixture can be carried out in the mainstream or in the sidestream. Figure 23-3 presents two examples of a circle system of an anesthesia machine with the location of the respiratory gas sensors at the Y-piece for direct measurements in the mainstream of the breathing system, or connected by a thin capillary tube or hose in the sidestream distant from the patient. (A circle system is part of the ventilation system in anesthesia machines dedicated to so-called semi-closed or closed anesthesia, which reuses the exhaled respiration gases after removing COj by an absorber.)... 

Various conventional medical applications for infrared gas analyzers have been described in the literature continuous analysis of COj in respired air (Domhorst et a/., 1953) alveolar CO2 measurement (Collier et al., 1955) measurement of CO2 in respired gas mixtures (Cullen et al., 1956) measurement of CO2 in respired gases containing cyclopropane and ether (Linde and Lurie, 1959) and application to anesthesia and respiratory physiology (Powell, 1965). 

Parris et al- -, have described a procedure utilizing a commercial atomic absorption spectrophotometer with a heated graphite tube furnace atomizer linked to a gas chromatograph for the determination of trimethylarsine in respirant gases produced in microbiological reactions. The overall GC-AA system used by these workers is illustrated in Figure 188. 

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