1 v. (various pagings) ; / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Faculty of Medicine, 1972

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This study examined the effects of lung expansion and changes in temperature on fluid movement by the lungs in the initial period after birth. In addition, experiments with amiloride support the belief that fluid reabsorption acts via a sodium transport mechanism. Lungs from fetal guinea pigs (56-67 days of gestation) were supported in vitro for three hours, and lung liquid production rates were measured using a dye dilution technique. The average production rate in the first hour of untreated preparations was 1.30 ±0.22 ml/kg body weight per hour, and this did not change significantly during the remainder of the experiment (n=30). This rate is comparable to secretion rates previously reported from chronically catheterized sheep. In 36 further preparations, the lungs were transferred from 37°C to fresh Krebs-Hanseleit saline at one of the following temperatures, for one hour (an ABA design): (a) 29°C; (b) 32°C; (c) 34°C; (d) 35°C; (e) 36°C; (f) 39°C. In all cases, the temperature change resulted in an immediate and significant fall in secretion. All lungs showed a tendency towards recovery when returned to starting conditions, except those subjected to a temperature increase. Reductions of 2-3°C, those normally seen in the delivery room, had the greatest effect and caused not only a decrease in secretion, but promoted fluid reabsorption. Amiloride at 10⁻⁶M had no effect on control preparations, but completely blocked the reabsorption stimulated by a temperature drop of 2°C. Expansion of the lungs, which occurs naturally as a newborn attempts to take its first breaths, was also examined. Thirty fetal lungs were expanded by one of the following amounts: (a) 18%; (b) 31%; (c) 43%; (d) 50%; (e) 72%. All expansions resulted in a significant fall in secretion rate, with the effect being proportional to the degree of expansion. Amiloride at 10⁻⁶M again blocked the strong reabsorption occurring with 70% expansion. Further studies investigated the possibility that expansion causes reabsorption via the local release of a substance occurring in the lungs. When one set of lungs was expanded in the presence of a second, unexpanded set, both showed a significant decrease in secretion, suggesting that the expanded lung had released some factor which affected the otherwise untreated lung. However, studies with α- and β- adrenergic blockers showed that it is unlikely the expanded lung was liberating either adrenaline or nor-adrenaline. The results of this study show that two changes which are likely to occur in the period immediately after birth, namely a 2-3°C decrease in core temperature, and lung expansion, may be important in promoting the vital reabsorption of fluid. They suggest that expansion may release substances locally in the lungs which stimulate this reabsorption, and that the fluid is removed from the potential air spaces via sodium transport mechanisms. / Science, Faculty of / Zoology, Department of / Graduate

To investigate the relationship between pulmonary diffusion limitation, ventilation-perfusion (VA/Q) mismatch, pulmonary transit times (PTT) and pulmonary gas exchange during exercise, 10 highly trained male athletes (age=26.4±4.4 years, Height=185.5±5.3cms, Weight=78.2±8.6 kg, V 02max=5.15±0.521-min-1) under went exercise testing at rest (R) and 150W, 300W and maximal exercise (372±22W), corresponding to an oxygen consumption (V0₂) of 0.41±0.09, 2.16±0.17, 4.32±0.35 and 5.13±0.50 1-min-1respectively, while trace amounts of six inert gases were infused via a peripheral vein. Arterial blood samples, mixed expired gas samples and metabolic data were obtained. Observed alveolar arterial difference ([A-a]D0₂(0)was calculated according to the alveolar gas equation. Indices of VA/Q mismatch: LogSDi and Log SDa and predicted [A-a]D0₂([A-a]DO₂(p)) were derived from 50 compartment model analysis of retentions and excretions of the inert gases. Additional indices of '/A/I,) mismatch: DISPR*, DISPE and DISPR*_E and inert gas alveolar difference ([A-a]D, R(A-a)D and E(A-a)D) were obtained directly from the inert gas data. One to two weeks later, the subjects underwent first pass radionuclide angiography using a Siemens ZLC wide field of view gamma camera. Following in vitro labeling with 99mTechnecium, 5-10 ml of the subject's blood, containing 10-20 mCi of activity, were injected at rest. First pass and post-static data were obtained on an ADAC 3003 computer and cardiac output was calculated using the Stewart Hamilton equation. PTT was determined using deconvolution and centroid methods. Gated radionuclide angiography was then performed at rest, 150, and 300W. On a separate occasion, first pass cardiac outputs and pulmonary transit times were obtained at maximal exercise. Mean arterial partial pressure of 0₂ (Pa0₂) decreased significantly from rest to 150W , and from 150 to 300W to a low value of 86±9 torn, before increasing to near resting values at maximal exercise. [A-a]D0₂(3) increased across each exercise levels however only the increase from 150 to 300 W was significant. The overall and perfusion-related indices of VA/Q mismatch showed a significant increase with exercise, mainly as a result of increasing perfusion of areas of high VA/Q [A-a]D0₂(0 was greater than predicted, becoming significant during heavy exercise, indicating diffusion limitation. Cardiac output increased from 6.9±0.9 1-min-1 (R) to 25.2±2.5 1-min-1 at 300W and 33.3±3.7 1-min-1 at maximal exercise. End diastolic volume increased from R to heavy exercise (p < 0.001), accompanied by a decrease in end systolic volume (p =0.05). Stroke volume and ejection fraction also increased significantly from R to 300W (p <0.001). Deconvolution PTT decreased from 9.32±1.41 s at rest to 2.91±0.30 s during max exercise and was highly correlated with centroid PTT both at rest (r=0.99, p<0.001) and during maximal exercise (r=0.96, p<0.001). PTT during maximal exercise was significantly correlated with Pa0₂ (1=0.65, p<0.05) and [A-a]D0₂(0)_[A-a]D0₂(p) (r=-0.60, p<0.05). Calculated pulmonary blood volume increased during maximal exercise by 57% over resting values to over 25% of total blood volume and when corrected for body surface area correlated significantly with Pa0₂ (r=0.69, p<0.05). There was a significant correlation between (A-a)D, PTT, the ventilatory equivalent for CO₂ and Pa0₂ during maximal exercise (r=0.94, p<0.01) allowing prediction of over 80% of the variance in Pa0₂ between subjects. These data indicate that highly trained athletes develop VA/Q mismatch accompanied by diffusion limitation during maximal exercise. Observed decrease in Pa0₂2 during high intensity exercise is the result of a complex interaction between VA/Q mismatch, hypoventilation and diffusion limitation secondary to shortened pulmonary transit.

No description available.

To investigate the relationship between pulmonary diffusion limitation, ventilation-perfusion (VA/Q) mismatch, pulmonary transit times (PTT) and pulmonary gas exchange during exercise, 10 highly trained male athletes (age=26.4±4.4 years, Height=185.5±5.3cms, Weight=78.2±8.6 kg, V 02max=5.15±0.521-min-1) under went exercise testing at rest (R) and 150W, 300W and maximal exercise (372±22W), corresponding to an oxygen consumption (V0₂) of 0.41±0.09, 2.16±0.17, 4.32±0.35 and 5.13±0.50 1-min-1respectively, while trace amounts of six inert gases were infused via a peripheral vein. Arterial blood samples, mixed expired gas samples and metabolic data were obtained. Observed alveolar arterial difference ([A-a]D0₂(0)was calculated according to the alveolar gas equation. Indices of VA/Q mismatch: LogSDi and Log SDa and predicted [A-a]D0₂([A-a]DO₂(p)) were derived from 50 compartment model analysis of retentions and excretions of the inert gases. Additional indices of '/A/I,) mismatch: DISPR*, DISPE and DISPR*_E and inert gas alveolar difference ([A-a]D, R(A-a)D and E(A-a)D) were obtained directly from the inert gas data. One to two weeks later, the subjects underwent first pass radionuclide angiography using a Siemens ZLC wide field of view gamma camera. Following in vitro labeling with 99mTechnecium, 5-10 ml of the subject's blood, containing 10-20 mCi of activity, were injected at rest. First pass and post-static data were obtained on an ADAC 3003 computer and cardiac output was calculated using the Stewart Hamilton equation. PTT was determined using deconvolution and centroid methods. Gated radionuclide angiography was then performed at rest, 150, and 300W. On a separate occasion, first pass cardiac outputs and pulmonary transit times were obtained at maximal exercise. Mean arterial partial pressure of 0₂ (Pa0₂) decreased significantly from rest to 150W , and from 150 to 300W to a low value of 86±9 torn, before increasing to near resting values at maximal exercise. [A-a]D0₂(3) increased across each exercise levels however only the increase from 150 to 300 W was significant. The overall and perfusion-related indices of VA/Q mismatch showed a significant increase with exercise, mainly as a result of increasing perfusion of areas of high VA/Q [A-a]D0₂(0 was greater than predicted, becoming significant during heavy exercise, indicating diffusion limitation. Cardiac output increased from 6.9±0.9 1-min-1 (R) to 25.2±2.5 1-min-1 at 300W and 33.3±3.7 1-min-1 at maximal exercise. End diastolic volume increased from R to heavy exercise (p < 0.001), accompanied by a decrease in end systolic volume (p =0.05). Stroke volume and ejection fraction also increased significantly from R to 300W (p <0.001). Deconvolution PTT decreased from 9.32±1.41 s at rest to 2.91±0.30 s during max exercise and was highly correlated with centroid PTT both at rest (r=0.99, p<0.001) and during maximal exercise (r=0.96, p<0.001). PTT during maximal exercise was significantly correlated with Pa0₂ (1=0.65, p<0.05) and [A-a]D0₂(0)_[A-a]D0₂(p) (r=-0.60, p<0.05). Calculated pulmonary blood volume increased during maximal exercise by 57% over resting values to over 25% of total blood volume and when corrected for body surface area correlated significantly with Pa0₂ (r=0.69, p<0.05). There was a significant correlation between (A-a)D, PTT, the ventilatory equivalent for CO₂ and Pa0₂ during maximal exercise (r=0.94, p<0.01) allowing prediction of over 80% of the variance in Pa0₂ between subjects. These data indicate that highly trained athletes develop VA/Q mismatch accompanied by diffusion limitation during maximal exercise. Observed decrease in Pa0₂2 during high intensity exercise is the result of a complex interaction between VA/Q mismatch, hypoventilation and diffusion limitation secondary to shortened pulmonary transit. / Graduate and Postdoctoral Studies / Graduate

Introduction: Respiratory tract symptoms (RTS), common in athletes during heavy training and after events, result in impaired readiness for events and race times. Since the 1980’s exercise immunologists have investigated the aetiological factors surrounding the development of exercise induced RTS in order to develop effective preventative strategies. A number of theories have been put forward and explored, such as increased susceptibility to infection, ‘run-away’ inflammatory response and reactivation of prior viral infection. It has been suggested that the mechanisms producing exercise induced inflammation could potentiate allergic responses in sensitized individuals and recently allergic response has been proposed as a potential contributor to exercise induced RTS. Certainly allergic reactions can produce a range of respiratory symptoms; however the relationship between allergic sensitization, allergic reaction and the incidence of post-exercise RTS has not been well defined. Objectives: The primary objective of this study was to document the incidence of RTS for two weeks before and two weeks after a three-day trail run and relate these to the general systemic and salivary immunological profile as well as atopic status of the participants. The secondary objective was to validate the use of the Phadiatop® assay as a predictor of allergy-associated post-race RTS in trail runners. Study Design and Methods: The study formed part of a larger, descriptive field study examining the physiological responses of trail runners during the Three Cranes Challenge, a multi-day 95 km event divided into three stages, in Karkloof, KwaZulu-Natal. Outcome measures examined included self- reported RTS over a 31 day period (pre, during and post race), as well as pre-race Phadiatop® status, salivary IgA (sIgA) concentrations and changes in concentrations of serum IgE (sIgE), cortisol, high sensitivity C-Reactive Protein (hs-CRP) and differential leukocyte counts. The haematological and salivary parameters were obtained at 8 time points before, during and after the event. A convenience sample of 22 individuals was used and two separate analyses were conducted on the data. The inclusion criteria of the first analysis were met by 14 participants. In this analysis, the incidence of RTS was related to each participant’s general immunological profile. Sixteen of the subjects met the inclusion criteria for the second analysis, in which their Phadiatop® status was related to their sIgE and blood eosinophil and basophil concentrations in order to establish the validity of the Phadiatop® assay in predicting the development of allergy–associated postexercise RTS in trail runners. Results: In the first analysis, 78.6 % (n=11) of subjects met the criteria for positive diagnosis of upper respiratory symptoms (URS) during the two week post-race period. In four subjects (36.4 %), URS appeared to be of inflammatory origin, but these were not linked to systemic markers of an allergic response. Of the URS positive subjects, six (54.5 %) presented with markers of infection, three (27.3 %) with markers of a de novo infection and three (27.3%) with a profile suggestive of reactivation of previous infection. Of those presenting with markers of infection 66.7 % (n=4) had concomitantly elevated levels of IgE suggestive of allergic response. There was, however, no evidence of isolated allergic reaction independent of other causes amongst the symptomatic subjects. In the second analysis, 75% (n=12) of runners presented with post-race RTS and seven of these were Phadiatop® positive. In four of the Phadiatop® positive RTS subjects, symptoms appeared to be of allergic origin. Although total IgE concentrations were significantly higher (p< 0.01) in Phadiatop® positive group, there was no significant difference between the eosinophil and basophil concentrations or post-race RTS of the positive and negative groups (p>0.05). Of the four subjects who did not develop RTS, three were Phadiatop® positive. Conclusion: Respiratory tract symptoms in trail runners have a multi-factorial aetiology. A link between concurrent markers of an allergic response and infection is common in symptomatic trail runners. The Phadiatop® assay does not accurately predict the incidence of allergic postexercise RTS in trail runners. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Westville, 2012.

The presence of cholesterol is critical in defining a dynamic lateral structure in pulmonary <p>surfactant membranes, including the segregation of fluid-ordered and fluid-disordered phases. <p>However, an excess of cholesterol has been associated with impaired surface activity both in <p>surfactant models and in surfactant from injured lungs. It has also been reported that surfactant <p>protein SP-C interacts with cholesterol in lipid/protein interfacial films. In the present study, we <p>have analyzed the effect of SP-C on the thermodynamic properties of phospholipid membranes <p>containing cholesterol and on the ability of lipid/protein complexes containing surfactant <p>proteins and cholesterol to form and re-spread interfacial films capable of producing very low <p>surface tensions upon repetitive compression-expansion cycling. We have also analyzed the effect of cholesterol on the <p>structure, orientation and dynamic properties of SP-C embedded in physiologically relevant <p>model membranes. <p><p> / Doctorat en Sciences / info:eu-repo/semantics/nonPublished