Thesis (Ph. D.)--Murdoch University, 1984.

Greyhounds were trained to gallop at maximal running speed on a treadmill constructed for the purpose. This speed considerably exceeded maximal aerobic speed and was termed supramaximal. A mask was used to collect expired gases into bags during runs of 7.5 to 60 seconds and over the first 8-10 minutes of the recovery period. Respiratory parameters measured included VE, V02' VC02', R, fR', VT' ventilatory equivalent of °2 uptake and ventilatory equivalent of CO2 production. Respiration was found to be synchronised with the gallop stride, enabling both a high fR and VT. Mean VE reached 6 1.kg-1.min-1. Mean V02 reached 143ml.kg-l.min-l during the 30-45 second segment of running. Lactic acid draining into the blood stream displaced CO2 from the bicarbonate buffer system, so that R rose above 1.0. The highest value of R, 2.3 occurred in the second minute of recovery. The alactacid debt of the greyhound was found to be higher than that of man but was repaid much more rapidly because of the greyhound's superior oxygen transport system. The cardiovascular system was studied using electromagnetic and thermodilution flowmeters, and a heart rate telemeter. Changes in blood pressure caused changes in the relationship of the very elastic aortic root and the electromagnetic transducer cuff so that accurate calibration was not possible. Reliable values of cardiac output were obtained by thermodilution. Parameters measured included HR, cardiac output, SV and PCV taken before, during and for 1 hour after running. The minimum HR whilst sleeping was also obtained, and averaged 42 b min .-1 The HR was highest during runs of 30 seconds, 318 plus/minus18 b min -1. After running it fell sharply to below 160 in the second minute of recovery then rose to 200b.min-l 10 minutes after 30 and 45 second runs. HR was close to resting levels 1 hour after running. PCV after 30 seconds of running was 63.5 + 2.1% and had returned to resting values by 1 hour. Cardiac output during high speed runs was 914 + 209ml.kg-l.min-l while SV at 2.9 + 0.6ml. kg-l was increased 32% above resting SV. Acid-base balance of jugular venous blood was studied. Comparisons with arterial samples taken at the same time showed a useful relationship of arterial and jugular venous blood for lactate, base excess and pH. The time taken for blood lactate to reach its peak value varied with the intensity and the duration of the run. The jugular venous blood lactate level after 45 of running peaked at 181 plus or minus l5mg.dl-l (7 minutes after seconds running) , pH fell to 7.094 plus or minus 0.27, base excess to -23.4 plus or minus 2.7 mEq.l-l and PC02 to 23 + 2 mm Hg. All values had returned to resting level 1 hour after the run. Oxygen consumption during running, alactacid debt, lactate production and distance covered were used to calculate total energy cost and relative contributions of energy sources and energy cost.m -1. Anaerobic sources were the main contributors in the first 15 seconds but in the 15-30 second segment aerobic sources supplied 53% of the energy required and in the 30-45 second segment, 79%. The energy source contributions to30 seconds of running were aerobic 30%, alactacid debt 19% and lactic acid 51%. The energy cost.m-l at supramaximal speeds was higher than predicted by formulae derived from studies of dogs at submaximal speeds. The first 7.5 seconds of running cost almost as much as the next 22.5 seconds, indicating a high cost of acceleration. This is the first quantification of the energy cost of acceleration reported. Compared to man, the greyhound has a very high oxygen uptake during sprinting. Man's major deficiencies as a sprinter are a low maximal heart rate, small heart relative to body size and low PCV. Sprinting impedes respiration in man but aids it in the greyhound. Calculations indicate that when man runs at supramaximal speed, it costs more per metre than predicted by formulae derived at submaximal speeds and that the energy cost of acceleration is of the same order as in the greyhound although man attains a much lower peak speed.

Four Greyhound dogs and six horses were utilized to study the physiological mechanisms associated with the development of an exercise training-induced hypervolemia. The animals were used in two separate experiments and were trained for 14 days on a treadmill ergometer and the data were used to formulate conclusions regarding the physiological and practical implications related to the phenomenon. The data reported in this dissertation indicated that exercise training will cause an expansion of the plasma volume in the Greyhound dog (+27%, P < 0.05) and the horse (+29.1% P < 0.05). Physiologically the result is similar in man, the dog, and the horse, however, the mechanisms by which this adaptation is reached appears to differ in each of the species. In the dog, water intake (+33%, P < 0.05) appears to be the primary mechanism for the increase in fluid volume. In the horse, renal control mechanisms (24-hr urine output -24.5%, P < 0.05) appear to be the primary mechanism with those that control the retention of solutes other than sodium predominating over those that control the reabsorption of sodium and water. Based upon the literature, it appears that in man, renal mechanisms predominate the hypervolemic response and mechanisms which control the conservation of sodium appear to be most active in the defense of the tonicity and volume of the vascular compartment. These species differences are important to the understanding of the physiology behind the onset of the training-induced hypervolemia and they provide pertinent information upon which decisions regarding the choice of animal models for future research.

A new general method is developed for the optimization of HPLC ternary or pseudo-quaternary mobile phases which are represented by the trilinear coordinate system. This method can predict the global optimum of the mobile phase composition. The global optimum composition along each edge of the triangle and the corresponding selectivity factor of the worst-separated peak pair(s) are used in this method. This method is named the weighted pattern comparison optimization method (WPCO) and is applicable for both known and unknown samples. The WPCO method is simpler than those currently in use. The WPCO method was tested by using 68 literature data sets whose separation response surfaces are different. Results of the WPCO method agree with the results obtained by the minimum α plot method and by the grid search method, and do so with substantially fewer experimental measurements. Compared with the 5% (in eluent composition) step size grid-search procedure, the WPCO method using the same step size reduces the experimental work by 75%. For further reducing the experimental work, the original WPCO method is simplified. In an ordinary HPLC separation, the separation factor and resolution are approximately proportional to the logarithm of the selectivity factor. Based on this, the separation factor replaces the logarithm of selectivity factor in the original WPCO method. This further reduces the experimental work and avoids the error introduced in the measurement of the column dead volume. The simplified WPCO method has been tested in the normal-phase and reversed-phase chromatography separation cases. The simplified WPCO method has been tested by using 27 literature data sets whose separation response surfaces are different. Results of the simplified and original WPCO methods are nearly identical when the capacity factors of the solutes of the worst-separated peak pairs are greater than 5. When the capacity factors are less than 5, the simplified WPCO method is satisfactory in less complex, less critical applications. Two new metabolites of nefopam have been separated from greyhound urine. In the separation process, flash chromatography is used for cleaning up and preseparating the samples in a single step. Compared with other techniques, experimental work is reduced. The structure of one of the newly discovered metabolites is determined using MS and NMR. The most probable structure of the other metabolite is determined using MS. The main metabolic pathways at different doses in greyhounds are studied. / Graduation date: 1991