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K B Saunders

Publications and source records attributed to K B Saunders.

86 records · Page 5Linked to original sources
PubMedDate not supplied

Chemoreceptor drives and short sleep-wake cycles during hypoxia: a simulation study.

We used a Grodins-type mathematical model of the cardio-pulmonary system to investigate the cycling behaviour of the respiratory system during hypoxia in response to changes of state between waking and sleeping, namely a diminution of respiratory chemosensitivity during sleep. Shifts between waking and sleeping were triggered by various combinations of threshold values for PAO2. Mild or moderate hypoxia was simulated by values of inspired O2 concentration between 13% and 16% (normal 21%). In mild or moderate hypoxia, reductions of overall respiratory gain from about 2 to 0.8 l.min-1 mmHg-1 at sleep onset will produce falls in PAO2 likely to cause sleep-wake cycles with oscillations in PAO2. The higher the arousal threshold (in relation to steady-state PAO2 during sleep), the shorter and more stable the sleep-wake cycles. As the arousal threshold is raised, and as hypoxia is exacerbated from mild (FIO2 = 16%) to moderate (FIO2 = 13%), the sleep-wake cycle length tends to converge to a value around one minute. The level and determinants of the "back-to-sleep" threshold are hard to define from presently available experimental data, but the level is not important in determining the length of the sleep-wake cycle compared to the arousal threshold. Alinearities in chemoreceptor feedback were introduced first by incorporating "drive" thresholds, to simulate central or obstructive apnoea. This produced larger oscillations in respiratory variables, but no change in cycle length. Chemoreceptor thresholds for PCO2 at the level of 38-39 mmHg did produce shorter ventilation cycles, down to about 20 s in length, but these were not related in any simple way to the resulting sleep-wake cycles. The combination of sleep state changes and chemoreceptor feedback alinearities can produce short sleep-wake cycles despite the diminution in chemoreceptor gain occurring in sleep.

Chemoreceptor Cells↗
PubMedDate not supplied

An in vitro model for cell-cell interactions.

Heterotypic cell-cell interactions appear to be involved in the control of development and function in a wide variety of tissues. In the vasculature, endothelial cells and mural cells (smooth muscle cells or pericytes) make frequent contacts, suggesting a role for intercellular interactions in the regulation of vascular growth and function. We have previously grown endothelial cells and mural cells together in mixed cultures and found that heterocellular contact led to endothelial growth inhibition. However, this mixed culture system does not lend itself to the examination of the effects of contact on the phenotype of the individual cell types. We have therefore developed a co-culture system in which cells can be co-cultured across a porous membrane, permitting intercellular contact while maintaining pure cell populations. Co-culture of endothelial cells and smooth muscle cells across membranes with pore sizes of 0.02, 0.4, 0.6, and 0.8 microns maintained the two cell types as homogeneous populations, whereas smooth muscle cells migrated across the membrane through pores of 2.0 microns. Vascular cell co-culture across membranes with 0.8-microns pores resulted in the inhibition of endothelial cell proliferation and the generation of conditioned media which inhibited endothelial cell growth The arrangement of the cells in this co-culture system mimics the in vivo orientation of vascular cells in which mural cells are separated from the abluminal surface of the endothelium by a fenestrated internal elastic lamina or basement membrane. Because this co-culture system maintains separable populations of cells in contact or close proximity allowing for biochemical and molecular analyses of pure populations, it should prove useful for the study of cell-cell interactions in a variety of systems.

Actins↗
PubMedDate not supplied

Effect on ventilation of carbon dioxide delivered in early inspiration in man.

Four subjects breathed an air-CO2 mixture, obtained by injecting pure CO2 0.4 l.min-1 into the inspiratory line of an open breathing circuit. The effects of injecting CO2 directly into the tubing (Fenn-Craig technique, FC), with a resulting large CO2 bolus in early inspiration, were compared with those of injecting into a mixing chamber (MC) and thus spreading the CO2 load more evenly over inspiration. Ensemble averaging of three experiments for MC and FC in each subject was used to clarify the relatively small changes in ventilation (V), about 5 l.min-1, and end-tidal PCO2 (PETCO2), about 5 mmHg, which were produced by the stimulus. Change in V and in PETCO2 were both systematically less for MC than FC, by about 1 l.min-1 and 0.5 to 1 mmHg respectively, suggesting that the CO2 load to the alveoli was larger for FC, with V then appropriately higher by the normal CO2 response. The increased CO2 load in FC could be accounted for by the lower proportion of CO2 left in the dead space, compared to MC. Thus, in man breathing air, no systematic effect on CO2 sensitivity was produced by an early inspiratory bolus of CO2.

Administration, Inhalation↗