The spleen has been shown to contract in apneic situations in humans as well as in other diving mammals, expelling its stored red blood cell content into circulation. This natural blood boosting may increase the circulating hemoglobin concentration (Hb) by up to 10%, which would enhance the oxygen carrying capacity and likely increase performance. However, the triggers of this response in humans have not been fully clarified. Study I was therefore focused on the effect of hypoxia as a trigger of spleen contraction. It was found that 20 min of normobaric hypoxic breathing evoked a substantial reduction in spleen volume showing that hypoxia is an important trigger for spleen contraction. Knowing the role of hypoxia, Study II compared two different hypoxic situations – a 2 min apnea and 20 min normobaric hypoxic breathing – which resulted in the same level of arterial hemoglobin desaturation. Apnea evoked a twice as great spleen volume reduction, implying that variables other than hypoxia were likely involved in triggering spleen contraction. This may be hypercapnia which is present during apnea but not during normobaric hypoxic breathing. Study III therefore investigated the effects of breathing gas mixtures containing different proportions of CO2 prior to maximal apneas. Pre-breathing mixtures with higher percentages of CO2 resulted in greater spleen contraction, thus demonstrating hypercapnia's likely role as a trigger in addition to hypoxia. Study IV explored whether an all-or-nothing threshold stimulus for triggering spleen contraction existed, or if contraction was graded in relation to the magnitude of triggering stimuli. Exercise was therefore performed in an already hypoxic state during normobaria. Rest in hypoxia produced a moderate spleen volume reduction, with an enhanced spleen contraction resulting after hypoxic exercise, with a concomitant increase in Hb. This implies that spleen contraction is a graded response related to the magnitude of the stimuli. This could be beneficial in environments with varying oxygen content or work loads. Study V examined the possibility that spleen contraction is part of the acclimatization to altitude, during an expedition to summit Mt Everest. The long-term high altitude exposure, combined with physical work on the mountain, had no effects on resting spleen volume but resulted in a stronger spleen contraction, when provoked by apnea or exercise. This indicates that acclimatization to altitude may enhance the contractile capacity of the spleen, which may be beneficial for the climber. From these studies I concluded that hypoxia is an important trigger for spleen contraction but that hypercapnia also contributes in apneic situations. The spleen contraction likely provides a graded expulsion of erythrocytes in response to these stimuli, causing a temporary increase in gas storage capacity that may facilitate activities such as freediving and climbing. The storage of erythrocytes during rest serves to reduce blood viscosity, which would also be beneficial for the climber or diver. The human spleen contraction appears to become stronger with acclimatization, with beneficial effects at altitude. Such an upgraded response could be beneficial both in sports and diseases involving hypoxia.

Studies were undertaken to determine the cardiac and ventilatory responses of restrained and unrestrained rainbow trout (Salmo gairdneri) to changes in inspired oxygen and carbon dioxide tensions. The role of blood oxygen carrying capacity in the control of ventilation was investigated, as well as the location and innervation of oxygen receptors activated by hypoxia. Ventilation volume (Vg) was measured directly in restrained fish using a ventilation chamber that separated inspired from expired water, the latter being collected in a graduated cylinder. In receptor localization experiments a wooden tongue depressor held vertically in the buccal cavity in the median plane divided water flows to the gills on each side of the fish. Thus, one set of gills could be irrigated with hyperoxic water to maintain arterial oxygen tension, while hypoxic water was passed over the other set of gills. Blood samples were obtained from cannulae implanted in both the dorsal aorta and right common cardinal vein. Vg increased in hypercapnea (inspired CO₂ tension (PICO₂) 0.5-2.0 kPa) due to increased "stroke volume (frequency remained constant), with higher levels of Vg recorded at higher C0₂ tensions. In fish exposed to PICO₂ levels of 0.5 and 0.9 kPa, raising the inspired oxygen tension (PIO₂) to 60.4 kPa eliminated the ventilatory response to hypercapnea. Hyperoxia had little or no effect on ventilatory responses to (PICO₂) levels of 1.5 and 2.0 kPa. Ventilation volume was inversely related to blood oxygen content (CaO₂) in trout. CaO₂ decreased and Vg increased during hypercapnea (PICO₂ 0.8 kPa), hypoxia (PIO₂12.4 kPa) and anaemia (haematocrit reduced from 22.3% to 14.3%), while CaO₂ increased and Vg decreased during hyperoxic hypercapnea (PIO₂ 60.4 kPa, PICO₂ 0.8 kPa). Increased Vg during hypercapnea is attributed to hypoxaemia produced by Bohr and Root off-shifts which result from increased blood CO₂ tension and reduced blood pH. Oxygen uptake remained constant during all experimental trials, indicating that the manoeuvre of increasing Vg is effective in relieving adverse effects of hypoxaemia. The significance of elevated Vg as a short-term adaptation to hypoxaemia is discussed, Heart rate decreased and ventilation increased in unrestrained fish exposed to gradual hypoxia (PIO₂ decreased from 20 kPa to 4 kPa) at 7°C and 16°C. The initial heart rate of fish acclimated to 16°C was higher than that of the 7°C group, but at the lowest level of PIO₂, heart rates of both groups dropped to the same level. Thus, the cardiac chronotropic response to hypoxia in trout is temperature independent. Receptors causing hypoxic bradycardia are located in the dorsal region of the first gill arch. Hypoxic bradycardia was eliminated by removing the first gill arch, or by sectioning the branches of cranial nerves IX and X innervating the arch. Blood flow through the arch does not appear to be necessary for this response, since ligation of the arch at its ventral insertion on the body wall did not affect hypoxic bradycardia. The pseudobranch has no role in cardiac control since interrupting the flow of blood through, and deafferentation of, the pseudobranch had no effect on the cardiac response to hypoxia. The biological significance of hypoxic bradycardia, and ventilatory-circulatory interaction during hypoxia, are discussed. Ventilatory responses to hypercapnea and hypoxia were unchanged after bilateral section of the nerves to the first gill arch. Receptors in the first gill arch thus have no role in control of ventilation during either hypercapnea or hypoxia. Possible locations for receptors responsible for control of ventilation are discussed. / Science, Faculty of / Zoology, Department of / Graduate

The 'exponential peeling' technique has been applied to minute ventilation and tidal volume transients occurring after the abrupt removal of 7,6 and 5% CO2 in inspired air. These transients, in many cases, were found to be composed of three exponential components, each contributing to the total ventilatory response and each having individual time responses. Gelfand and Lambertsen (1973) have attributed these components to the peripheral chemoreceptors as a group and to two central chemoreceptors. Statistical analysis to determine the constancy of the contribution of the three components over the the range of CO2 values studied showed that, although the values for each at the different stimulus levels were not significantly different, the great subject-to-subject variation in the data precluded a firm conclusion about the constancy of the components. Because of a number of considerations it was concluded that exponential peeling of respiratory transients following abrupt removal of CO2 inhalation is not a satisfactory way to approach the problem of the numbers, relative contributions and time responses of the various receptor groups comprising the respiratory controller.

No description available.

No description available.

M.S.

The present research examined respiratory responses of blue crabs to long term (4, 13, and 21 days) hypercapnic hypoxia in freshwater at 23 C. Hypoxic conditions (50-60 & 75-85 mmHg O2) were induced by allowing the crabs to consume their oxygen supply, resulting in a hypercapnic induced decrease in pH that remained through the exposure. Postbranchial hemolymph responses to hypoxia/hypercapnia in freshwater demonstrate decreases in PO2, increases in PCO2, and decreases in pH. Lactate levels decreased over time, but hemocyanin concentration was highly variable with no trends. PH, lactate, and hemocyanin observations also demonstrated high variability and a variety of different responses in individual crabs. There was no evidence of improving oxygen transport abilities. Despite varying responses high mortality rates were observed. The high mortality rate suggests blue crabs are not able to survive the multiple stress of hypoxia/hypercapnia along with the stress of living in freshwater. The mortality rates observed are much greater than previous blue crab hypoxic studies in saltwater. Elevated mortality may result from a failure of oxygen transport, acid-base balance or ion regulation.

Goldfish undergo an adaptive morphological change in their gills involving the reversible growth and loss of a mass of cells (interlamellar cell mass, ILCM) in between the lamellae depending on oxygen demand, which can be altered by the environment or metabolic demands of the individual. The ILCM contributes to decreased passive Na+ efflux across the gill. Active uptake is maintained by the re-distribution of the ionocytes expressing Na+-uptake relevant genes (NHEs and H+-ATPase) to the outer edge of the ILCM where they can establish contact with the external environment and/or lamellar epithelium. This adaptation is thought to be partly responsible for the extreme anoxia tolerance demonstrated by goldfish, which they experience on a seasonal basis living in a pond environment. Hypoxia and hypercapnia are frequently encountered in such freshwater environments and as such, the effect of the ILCM on the capacity for acid-base regulation was evaluated. Differences in the time course of acid excretion to the environment without effect on systemic pH regulation were likely the result of the ILCM.

Cerebral autoregulation is an intrinsic physiological response that maintains a constant cerebral blood flow (CBF) despite dynamic changes in the systemic blood pressure. Autoregulation is achieved through changes in the resistance of the small blood vessels in the brain through reflexive vasodilatation and vasoconstriction. Cerebrovascular reactivity (CVR) is a measure of this response. CVR is defined as a change in CBF in response to a given vasodilatory stimulus. CVR therefore potentially reflects the vasodilatory reserve capacity of the cerebral vasculature to maintain a constant cerebral blood flow. A decrease in CVR (which is interpreted as a reduction in the vasodilatory reserve capacity) in the vascular territory downstream of a larger stenosed supply artery correlates strongly with the risk of a hemodynamic stroke. As a result, the use of CVR studies to evaluate the state of the cerebral autoregulatory capacity has clinical utility. Application of CVR studies in the clinical scenario depends on a thorough understanding of the normal response. The goal of this thesis therefore was to map CVR throughout the brain in normal healthy individuals using Blood Oxygen Level Dependant functional Magnetic Resonance Imaging (BOLD MRI) as an index to CBF and precisely controlled changes in end-tidal partial pressure of carbon dioxide (PETCO2) as the global flow stimulus.

Cerebral autoregulation is an intrinsic physiological response that maintains a constant cerebral blood flow (CBF) despite dynamic changes in the systemic blood pressure. Autoregulation is achieved through changes in the resistance of the small blood vessels in the brain through reflexive vasodilatation and vasoconstriction. Cerebrovascular reactivity (CVR) is a measure of this response. CVR is defined as a change in CBF in response to a given vasodilatory stimulus. CVR therefore potentially reflects the vasodilatory reserve capacity of the cerebral vasculature to maintain a constant cerebral blood flow. A decrease in CVR (which is interpreted as a reduction in the vasodilatory reserve capacity) in the vascular territory downstream of a larger stenosed supply artery correlates strongly with the risk of a hemodynamic stroke. As a result, the use of CVR studies to evaluate the state of the cerebral autoregulatory capacity has clinical utility. Application of CVR studies in the clinical scenario depends on a thorough understanding of the normal response. The goal of this thesis therefore was to map CVR throughout the brain in normal healthy individuals using Blood Oxygen Level Dependant functional Magnetic Resonance Imaging (BOLD MRI) as an index to CBF and precisely controlled changes in end-tidal partial pressure of carbon dioxide (PETCO2) as the global flow stimulus.