Biomedical subjects

David J Doolette

Publications and source records attributed to David J Doolette.

4 recordsLinked to original sources

PubMed2005

Perfusion-diffusion compartmental models describe cerebral helium kinetics at high and low cerebral blood flows in sheep.

This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood:tissue helium exchange in the brain. Helium has different physiochemical properties from previously studied gases, and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Helium kinetics across the cerebrum were determined during and after 15 min of helium inhalation, at separate low and high steady states of cerebral blood flow in seven sheep under isoflurane anaesthesia. Helium concentrations in arterial and sagittal sinus venous blood were determined using gas chromatographic analysis, and sagittal sinus blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion-diffusion compartmental models of the brain were estimated by simultaneous fitting of the models to the sagittal sinus helium concentrations for both blood flow states. Purely perfusion-limited models fitted the data poorly. Models that allowed a diffusion-limited exchange of helium between a perfusion-limited tissue compartment and an unperfused deep compartment provided better overall fit of the data and credible parameter estimates. Fit to the data was also improved by allowing countercurrent diffusion shunt of helium between arterial and venous blood. These results suggest a role of diffusion in blood:tissue helium equilibration in brain.

Animals↗

PubMed2003

Biophysical basis for inner ear decompression sickness.

Isolated inner ear decompression sickness (DCS) is recognized in deep diving involving breathing of helium-oxygen mixtures, particularly when breathing gas is switched to a nitrogen-rich mixture during decompression. The biophysical basis for this selective vulnerability of the inner ear to DCS has not been established. A compartmental model of inert gas kinetics in the human inner ear was constructed from anatomical and physiological parameters described in the literature and used to simulate inert gas tensions in the inner ear during deep dives and breathing-gas substitutions that have been reported to cause inner ear DCS. The model predicts considerable supersaturation, and therefore possible bubble formation, during the initial phase of a conventional decompression. Counterdiffusion of helium and nitrogen from the perilymph may produce supersaturation in the membranous labyrinth and endolymph after switching to a nitrogen-rich breathing mixture even without decompression. Conventional decompression algorithms may result in inadequate decompression for the inner ear for deep dives. Breathing-gas switches should be scheduled deep or shallow to avoid the period of maximum supersaturation resulting from decompression.

Adult↗

PubMedDate not supplied

A quantitative alternative to the hysteresis plot for measurement of drug transit time.

INTRODUCTION: Hysteresis plots can be used to examine pharmacokinetic data in which there is a transport delay between drug concentrations at two sites in the body (e.g., in blood entering and leaving an organ). However, the area enclosed by the hysteresis "loop" does not provide quantitative information about the magnitude of the delay. METHODS: A quick, graphical, and model independent alternative to the hysteresis plot (an "area fraction plot") was developed for a spreadsheet program on a personal computer. It has the advantage that the area enclosed by the "loop" is the mean transit time (MTT) of the transport delay. The method was based on plotting the cumulative area under the concentration-time curve as a fraction of the total area under curve for each site, and is a type of moment analysis. The method is described and was validated by application to simulated data sets. It was also applied to previously published data to calculate the MTT of lidocaine in the lungs and hindquarters of conscious, instrumented sheep. RESULTS: The validation process showed the area fraction plot was relatively insensitive to integration errors even with moderately noisy data sets. However, failing to analyse the data up to the time point where pseudo-equilibrium was re-established could result in potentially large underestimates of the transit time. The MTT of lidocaine (mean+/-S.E.M.) in the lungs of five sheep was rapid (0.61+/-0.15 min), and 14.2+/-3.1% of the lidocaine was retained in the lungs. The values were in good agreement with values obtained via structural modelling of the same data. The MTT of lidocaine in the hindquarters was 10.6+/-0.9 min, and the retention was 25.2+/-3.1%. DISCUSSION: The method can be used in the same situations as a hysteresis plot, but provides additional quantitative information about the transport delay causing the hysteresis.

Animals↗

PubMedDate not supplied

Brain pharmacokinetics of lignocaine before and following intravenous perfluorocarbon emulsion infusion in sheep.

1. Perfluorocarbon emulsions have potential medical applications, particularly as temporary oxygen carriers and are likely to be coadministered with other intravenous drugs. It is possible that perfluorocarbon emulsions may alter the disposition of other drugs in the body. 2. In the present study, we examined the brain pharmacokinetics of a 5 min infusion of 100 mg lignocaine in three chronically instrumented sheep before and after the administration of a new investigational perflurocarbon emulsion (Oxygent; Alliance Pharmaceutical, San Diego, CA, USA). 3. The rate constant for the blood : brain equilibration of lignocaine was larger after perflubron administration. This change could not be attributed to a change in brain blood flow and, therefore, may be the result of a change in the free fraction of lignocaine in the blood.

Animals↗