No description available.

The metabolic and biochemical adaptations which set the endurance limit in skeletal muscle and are modified by physical training, and those which set the fatigue limits in conditions of chronic hypoxia, are not completely understood. Therefore, the purpose of this study was to measure the key metabolites involved in the control of oxidative and glycolytic metabolism, during the elevated metabolic demands of exercise, in subject groups which were separated by distinct differences in their training status or by their exposure to chronic hypobaric hypoxia. Since repeated measures of the key metabolites involved in energy metabolism (PCr, Pi, ATP) and intracellular pH (pHm) would be exceedingly difficult using the conventional muscle needle biopsy technique, ³¹P NMR was selected as an appropriate, noninvasive method for measuring these metabolites. Two separate exercise models were developed for use within a 1.0 m bore NMR machine. An electrical stimulation model using the rectus femoris muscle was developed and the factors which influenced reliability and reproducibility of the data were determined. In addition, a dynamic exercise model was developed in which the gastrocnemius muscle was exercised in a mechanical calf ergometer. The results of the experiments using the electrical stimulation model indicate that RF coil geometry, stimulation intensity and duty cycle, electrode placement, and subject tolerance require very close control for the model to be reliable. It is felt that this model is best suited for experiments which require a within-subject design and is ideally suited for experimental or therapeutic intervention studies. The calf ergometer was used to compare sedentary lowlanders, marathon and ultramarathon runners, power trained athletes, and Quechua Indians, native to altitudes of 4,200 m in the Andes, before and after deacclimation to sea level. It was found that the Andean natives did not possess a standard physiological phenotype with respect to aerobic and anaerobic capacities. In addition, given the Andean's very low anaerobic capacity and intermediate aerobic capacity, this group performed calf work equivalent to that of highly trained endurance and power athletes. Moreover, pHm, PCr, Pi, and ATP showed equivalent perturbation at fatigue and in recovery compared with the marathon runners but considerably less perturbation than was found in the power trained athletes who possess equivalent aerobic capacities but far greater anaerobic capacities. NMR derivable estimates of the phosphorylation potential in this study support the theory that closer coupling between ATP supply-ATP demand may be responsible for reduced kinetic and thermodynamic activation of mitochondrial metabolism seen in the Andean natives. / Science, Faculty of / Zoology, Department of / Graduate

Embryos from the annual killifish Austrofundulus limnaeus have a unique and unequalled ability among vertebrates to withstand extended periods of anoxia (maximum lethal time to 50% mortality of 65 days at 25°C). In addition, tolerance of anoxia is gained and subsequently lost during the normal development of this species. Thus, anoxia tolerant and anoxia sensitive individuals can be compared within the same species, making A. limnaeus an excellent model for studying the molecular changes associated with survival of oxygen deprivation in vertebrates. The aim of this project is to analyze the molecular changes associated with anoxia tolerance in the embryos of A. limnaeus. Understanding how the cells of these embryos become tolerant to anoxia will aid in identifying novel therapeutic targets to reduce cell death following periods of ischemia in heart, brain or other tissues. Three major analyses were used to investigate the molecular changes associated with anoxia tolerance in this species. The first was a cell cycle and cell cycle arrest analysis using flow cytometry along with an immunoblot analysis of both positive and negative regulators of cell cycle progression. The second was a cell death analysis utilizing caspase-3/7 activity as well as TUNEL staining. The third was an immunoblot analysis of three different post-translational modifers (ubiquitin, SUMO-1 and SUMO-2/3). The overall findings from this study indicate that the embryos of A. limnaeus do indeed experience some degree of cellular stress (i.e. increase in ubiquitinated proteins, increase in p53 expression, evidence of DNA damage from TUNEL staining and increases in caspase activity) in response to anoxic treatment, even in their most protective state of diapause II. However, despite these observations, the whole organisms are still able to recover from anoxia and do not succumb to death. The overall low levels of TUNEL-positive cells and caspase activity relative to the positive controls indicates that the damage accrued in response to anoxic treatment is minimal. It appears that embryos are able to either "sacrifice" a certain portion of cells or they are able to repair the damage required for resumed development following anoxia.

No description available.

Thesis (MSc)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: Chapter 1 presents a general literature review on the acute isocapnic hypoxic ventilatory response (HVR). The main findings from Chapter 2 indicate that our modified breathing circuit effectively measured the HVR while maintaining isocapnia. The measured ventilatory variables changed significantly with repeated short-term exposure to hypoxia over a 30-minute period, and the within- and between-day variability did not differ significantly. Furthermore, the variability in the HVR response (as measured by the coefficient of variation, (CV» amounted to approximately 27% between tests in both parameters. Repeated measures are recommended in future determinations of the HVR. In Chapter 3 the main findings were that hypoxic sensitivity does not differ between Caucasian and Xhosa sea-level populations in South Africa, and that ventilatory components in both normoxia and hypoxia differed between these two populations. Two distinct patterns of breathing were evident: shallow, rapid breathing among Xhosa subjects, and deeper, slower breathing among Caucasians. Moreover, lower arterial oxygen saturation levels during hypoxia among Xhosa subjects suggest that these two patterns of breathing differ in the effectiveness with which they oxygenate the blood. Inter-individual variation in HVR within each population is of the same high magnitude as that reported in the literature (Beall et al., 1997), further supporting the use of repeated measures in future studies. As previously reported (Sahn et al., 1977, Reeves et al., 1993), in Chapter 3 I document a significant correlation between HVR and partial pressure of end-tidal CO2 (PETCO). Future studies of HVR should consider PETCO2 as a covariate, despite the fact that my analyses of covariance (ANCOV A) showed no inter-population differences in HVR. In Chapter 4 I report that regression analysis shows that the HVR of parents is not a predictor of that of their offspring. No significant heritability was evident for any of the additional key variables of hypoxic VE ,hypoxic Sa02, and the CV for HVR, but a priori analyses showed that I tested too few subjects to be able to demonstrate heritability (or the lack thereof) conclusively by means of regression analyses. Importantly, repeatability estimates within populations (86 %) revealed that despite its high variability, the HVR is highly repeatable, and therefore remains a useful comparative research tool for studies of human adaptation to hypoxia. / AFRIKAANSE OPSOMMING: Hoofstuk 1 gee 'n algemene literatuuroorsig van die akute isokapniese hipoksiese ventilatoriese reaksie (HVR). Die hoofbevindinge uit Hoofstuk 2 dui aan dat ons gemodifiseerde asemhalingsbaan HVR effektief meet terwyl isokapniese toestande gehantaaf word. Die ventilatoriese veranderlikes gemeet, het betekenisvol verskil met herhaalde korttermyn blootstelling aan hipoksie in a 30-minuut periode, en die binne- en tussen-daagse afwykbaarheid het nie betekenisvol verskil nie. Verder het die afwykbaarheid van die HVR reaksie (soos bepaal deur die koëffisiënt van variasie (KV)) ongeveer 27 % beloop tussen toetse van beide parameters. Herhaalde metings word vir toekomstige bepalings van die HVR voorgestel. In Hoofstuk 3 was die hoofbevindinge dat hipoksiese sensitiwiteit nie verskil tussen Kaukasiese- en Xhosa- seevlak populasies in Suid-Afrika nie, en dat ventilatoriese komponente in beide normoksie en hipoksie verskillend was tussen hierdie twee populasies. Twee definitiewe asemhalingspatrone was duidelik merkbaar: vlak, vinnige asemhaling in Xhosa proefpersone, en dieper, stadiger asemhaling in Kaukasiërs. Verder het laer arteriële suurstof versadigingsvlakke gedurende hipoksie in Xhosa proefpersone daarop gedui dat hierdie twee asemhalingspatrone moontlik verskil in hul effektiwiteit om die bloed met suurstof te verryk. Inter-individuele variasie in HVR binne elke populasie was van dieselfde groot omvang as wat in die literatuur gerapporteer word (Beall et al., 1997), wat die gebruik van herhaalde metings in toekomstige studies verder ondersteun. Soos voorheen gerapporteer (Sahn et al., 1977, Reeves et al., 1993), dokumenteer ek in Hoofstuk 3 'n merkbare korrelasie tussen HVR en parsiële druk van eind-tidale CO2 (PET CO2 ). Verdere HVR studies behoort PET CO2 as a kovariant te beskou, ten spyte van die feit dat my analise van kovariansie (ANCOV A) geen inter-populasie verskille in HVR getoon het nie. In Hoofstuk 4 rapporteer ek dat regressie analise bewys dat die HVR van ouers nie 'n voorspeller van dié van hul kinders is nie. Geen betekenisvolle oorerflikheid was duidelik vir enige van die addisionele sleutelveranderlikes van hipoksiese VE ,hipoksiese Sa02, of die KV van HVR nie, maar 'n vorige analise het getoon dat ek te min proefpersone getoets het om oorerflikheid (of die gebrek daaraan) m.b.v. regressie analises te kan demonstreer. Dit is belangrik dat intra-populasie herhaalbaarheidsskattings (86 %) getoon het dat ten spyte van sy hoë afwykbaarheid, die HVR hoogs herhaalbaar is, en daarom 'n nuttige vergelykende navorsingshulpmiddel is vir studies rakende menslike aanpassing by hipoksie.

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Obstetrics and Gynaecology / Master / Master of Philosophy

published_or_final_version / abstract / Physiology / Master / Master of Philosophy

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy