William J. Dorson

Instrumentation and Control Techniques for Dynamic Response Experiments in Living Tissue

The development of Polarographic micro oxygen electrodes with tips less than 10μ has allowed the study of cellular and tissue oxygen levels in response to dynamic changes. Several investigators have recorded the in vivo behavior of pO2 in the cerebral cortex tissue when arterial pO2 was made to vary by a step change in the respired O2 concentration. Of particular note are the reports by Bicher (1) in the cat cerebral cortex and Metzger in the cortex of rats (2). A transient overshoot in tissue pO2 was observed during recovery from a one-minute induced hypoxia. This behavior is not predicted directly from first order models with constant metabolism (3). Subsequent analysis ascribed this behavior to delayed brain blood flow transients (4), but instantaneous flow rates were not recorded during the cited experiments.

Dynamic Hypoxic Hypoxemia in Brain Tissue: Experimental and Theoretical Methodologies

An experimental system was assembled to study feline cerebral cortex cellular and extracellular pO2 response to rapid changes in carotid artery oxygen levels. The system has been described in prior articles in this series and elsewhere (Bogue and Dorson, 1973; Dorson and Bogue, 1973; Dorson and Bogue, 1976; Bogue, 1974). Changes in carotid artery oxygen level could be accomplished either by varying the ventilatory gas composition or by a carotid-jugular computer controlled exchange method. The latter technique involved cannulation of both internal carotid arteries and jugular veins. All other perfusion routes were supressed by compression. Relatively open flow was allowed in both directions with exchange between venous and arterial blood on an equal volume flow basis. This system resulted in the most rapid possible input change while maintaining close to normal physiological function. Many different types of changes were investigated, and this report will concentrate on oscillatory inputs caused by both the ventilation gas and blood exchange methods. No difference in response was noted up to the upper frequency limit of the ventilation method of 0.1 Hz while the exchange method was capable of 1.0 Hz oscillations.

Controlling factors in hemofiltration

Abstract Ultrafiltration of bovine plasma and blood (hemofiltration) was performed in a dual-parallelmembrane test device over a wide range of hematocrits (0–85%), plasma protein concentrations (3–20 gm%), channel heights (0.022–0.073 cm) and flow rates. The plasma ultrafiltration data was used to determine film theory equation constants by regression techniques similar to that which had been done by others in the past. The ratios of hemofiltration to plasma ultrafiltration rates were then correlated by an independent analytical function of hematocrit, total protein concentration, and the superficial wall shear rate. The filtration flux ratio has a Fricke equation limit at low shear rates which would be below unity while a maximum filtration flux ratio greater than one was observed (and correlated) at high shear rates with hematocrits below 42%. The form of the hemofiltration correlation was also applied to previously published augmentation data in a pure shear field without plasma proteins. The design ramifications of the correlation include the determination of when addition augmentation methods are needed. The combination of both plasma ultrafiltration and hemofiltration correlations show how each variable affects and controls hemofiltration. The correlations are for small percentages of the incoming flow being filtered. For large flow fractions being filtered the correlations would have to be integrated along the axial length combined with mass balances. The hemofiltration equations can yield slightly lower fluxes at the lowest channel heights and slightly higher fluxes for the larger channel heights, presumably due to the Fahraeus—Lindqvist effect. The channel heights and shear rates utilized included conditions where this effect should be considerable as well as conditions where it should not be present. The regression techniques were applied to all the data.

Response of feline brain tissue to oscillating arterial pO2.

An experimental system has been developed to investigate the transient response of tissue and cellular pO2 to dynamic changes in perfusion. The in-vivo tissue transients resulting from short episodes of respirator-induced hypoxia were followed in the cerebral cortex of cats while simultaneously measuring tissue pO2, total arterial pO2 and flow rate, venous pO2, and cell action-potential. The system was capable of producing, recording, and correlating oscillations induced by either respirator variations or a computer controlled exchange of venous and arterial blood.