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Biomedical subjects

D J Doolette

Publications and source records attributed to D J Doolette.

At least 19 recordsLinked to original sources
PubMed2005

Countercurrent compartmental models describe hind limb skeletal muscle helium kinetics at resting and low blood flows in sheep.

AIMS: This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood : tissue helium exchange in a predominantly skeletal muscle tissue bed in the sheep hind limb. 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. METHODS: Helium kinetics across skeletal muscle were determined during and after 20 min of helium inhalation, at separate resting and low steady-states of femoral vein blood flow in six sheep under isoflurane anaesthesia. Helium concentrations in arterial and femoral vein blood were determined using gas chromatographic analysis and femoral vein blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion-diffusion compartmental models of skeletal muscle were estimated by simultaneous fitting of the models to the femoral vein helium concentrations for both blood flow states. RESULTS: A model comprising two parallel perfusion-limited compartment models fitted the data well but required a 51-fold difference in relative compartment perfusion that did not seem physiologically plausible. Models that allowed a countercurrent diffusion exchange of helium between arterial and venous vessels outside of the tissue compartments provided better overall fit of the data and credible parameter estimates. CONCLUSIONS: These results suggest a role of arterial-venous diffusion in blood : tissue helium equilibration in skeletal muscle.

Administration, Inhalation↗
PubMed2003

Evaluation of decompression safety in an occupational diving group using self reported diving exposure and health status.

BACKGROUND: Many occupational diving groups have substantially different diving patterns to those for which decompression schedules are validated. AIMS: To evaluate tuna farm occupational diving practice against existing decompression models and describe a method for collecting and modelling self reported field decompression data. METHODS: Machine readable objective depth/time profiles were obtained from depth/time recorders worn by tuna farm occupational divers. Divers' health status was measured at the end of each working day using a self administered health survey that produces an interval diver health score (DHS) with possible values ranging from 0 to 30. Depth/time profiles were analysed according to existing decompression models. The contribution of diving exposure and between diver variability to DHS was evaluated using linear regression. RESULTS: The mean risk of decompression sickness was calculated as 0.005 (SD 0.003, n = 383). The mean DHS following diving was 3 (SD 2, n = 383) and following non-diving activities was 1 (SD 1, n = 41). After accounting for between diver variability in intercept, DHS was found to increase one unit for every 1% increase in the risk of decompression sickness. CONCLUSIONS: A method has been established for the collection and analysis of self reported objective decompression data from occupational diving groups that can potentially be used as the basis for development of purpose designed occupational diving decompression schedules.

Decompression↗
PubMed2003

Health outcome following multi-day occupational air diving.

Acclimatization to decompression stress has been reported in caisson workers and helium-oxygen divers; however the alternative notion that the risk of decompression sickness increases with successive days of diving is widespread. We examined 201 multi-day series of 2 to 29 diving days identified retrospectively in a database of occupational air dives for evidence of acclimatization or sensitization. Decompression related health status was measured using a self-administered diver health survey; resulting scores were analyzed by linear modelling. Daily diving consisted of 1-3 dives each to mean maximum depth of 17.2 (SD 3.9) meters seawater for a mean duration of 23 (SD 17) min. Daily diver health scores increased with calculated daily risk of decompression sickness but were not influenced by the order of dives in multi-day series. Poor health outcome indicated by treated decompression sickness and diver health scores > 8 occurred early in multi-day series. There was no evidence of sensitization to decompression stress whereas the timing of poor health outcomes suggests an element of acclimatization.

Analysis of Variance↗
PubMed2003

Measurement of fatigue following 18 msw dry chamber dives breathing air or enriched air nitrox.

Many divers report less fatigue following diving breathing oxygen rich N2-O2 mixtures compared with breathing air. In this double blinded, randomized controlled study 11 divers breathed either air or Enriched Air Nitrox 36% (oxygen 36%, nitrogen 64%) during an 18 msw (281 kPa(a)) dry chamber dive for a bottom time of 40 minutes. Two periods of exercise were performed during the dive. Divers were assessed before and after each dive using the Multidimensional Fatigue Inventory-20, a visual analogue scale, Digit Span Tests, Stroop Tests, and Divers Health Survey (DHS). Diving to 18m produced no measurable difference in fatigue, attention levels, ability to concentrate or DHS scores, following dives using either breathing gas.

Adult↗
PubMed2001

Diffusion-limited tissue equilibration and arteriovenous diffusion shunt describe skeletal muscle nitrous oxide kinetics at high and low blood flows in sheep.

This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood : tissue inert gas exchange in skeletal muscle. Nitrous oxide kinetics in a hind limb skeletal muscle bed were determined during and after 20 min of nitrous oxide inhalation, at separate low and high steady states of hind limb blood flow in five sheep under halothane anaesthesia. Nitrous oxide concentrations in arterial and femoral vein blood were determined using gas chromatographic analysis and femoral vein blood flow was monitored continuously. Parameters and model selection criteria of various perfusion- or diffusion-limited structural models of skeletal muscle were estimated by simultaneous fitting of the models to the mean observed femoral vein nitrous oxide concentration for both blood flow states. Purely perfusion-limited models fit the data poorly. Models that allowed a diffusion-limited exchange of nitrous oxide between a perfusion-limited tissue compartment and an unperfused deep compartment provided better overall fit of the data and credible parameter estimates. The data was best described by allowing, in addition to diffusion-limited tissue equilibration, counter current diffusion of nitrous oxide between arterial and venous blood. The level of tissue blood flow modifies the magnitudes of both these diffusion effects. These results suggest a dual role of diffusion in blood : tissue inert gas equilibration in skeletal muscle.

Algorithms↗
PubMed2001

Increased cerebral blood flow and cardiac output following cerebral arterial air embolism in sheep.

1. The effects of cerebral arterial gas embolism on cerebral blood flow and systemic cardiovascular parameters were assessed in anaesthetized sheep. 2. Six sheep received a 2.5 mL injection of air simultaneously into each common carotid artery over 5 s. Mean arterial blood pressure, heart rate, end-tidal carbon dioxide and an ultrasonic Doppler index of cerebral blood flow were monitored continuously. Cardiac output was determined by periodic thermodilution. 3. Intracarotid injection of air produced an immediate drop in mean cerebral blood flow. This drop was transient and mean cerebral blood flow subsequently increased to 151% before declining slowly to baseline. Coincident with the increased cerebral blood flow was a sustained increase in mean cardiac output to 161% of baseline. Mean arterial blood pressure, heart rate and end-tidal carbon dioxide were not significantly altered by the intracarotid injection of air. 4. The increased cardiac output is a pathological response to impact of arterial air bubbles on the brain, possibly the brainstem. The increased cerebral blood flow is probably the result of the increased cardiac output and dilation of cerebral resistance vessels caused by the passage of air bubbles.

Animals↗
PubMed2001

Positive reform of tuna farm diving in South Australia in response to government intervention.

OBJECTIVES: Much of the tuna harvested in South Australia since 1990 has involved "farming" techniques requiring the use of divers. From 1993 to 1995, 17 divers from this industry were treated for decompression illness (DCI). In response, the State Government introduced corrective strategies. A decrease in the number of divers presenting for treatment was subsequently recorded. Consequently, the hypothesis was tested that the government intervention resulted in a decrease in the incidence of DCI in the industry and an improved clinical outcome of divers with DCI. METHODS: The incidence of treated DCI in tuna farm divers was estimated from the number of divers with DCI treated and the number of dives undertaken extrapolated from a survey of the industry in 1997-8. General health was measured in the tuna farm diving population by a valid and reliable self assessment questionnaire. The outcome of the divers treated for DCI was analysed with a modified clinical severity scoring system. RESULTS: The apparent incidence of treated DCI has decreased in tuna farm divers since the government intervention. The evidence supports a truly decreased incidence rather than underreporting. The general health of the tuna farm divers was skewed towards the asymptomatic end of the range, although health scores indicative of DCI were reported after 1.7% of the dives that did not result in recognised DCI. The clinical outcome of the divers treated since the intervention has improved, possibly because of earlier recognition of the disease and hence less time spent diving while having DCI. CONCLUSIONS: The government intervention in the tuna industry in South Australia has resulted in a reduced incidence of DCI in the industry.

Adult↗
PubMed2001

The physiological kinetics of nitrogen and the prevention of decompression sickness.

Decompression sickness (DCS) is a potentially crippling disease caused by intracorporeal bubble formation during or after decompression from a compressed gas underwater dive. Bubbles most commonly evolve from dissolved inert gas accumulated during the exposure to increased ambient pressure. Most diving is performed breathing air, and the inert gas of interest is nitrogen. Divers use algorithms based on nitrogen kinetic models to plan the duration and degree of exposure to increased ambient pressure and to control their ascent rate. However, even correct execution of dives planned using such algorithms often results in bubble formation and may result in DCS. This reflects the importance of idiosyncratic host factors that are difficult to model, and deficiencies in current nitrogen kinetic models. Models describing the exchange of nitrogen between tissues and blood may be based on distributed capillary units or lumped compartments, either of which may be perfusion- or diffusion-limited. However, such simplistic models are usually poor predictors of experimental nitrogen kinetics at the organ or tissue level, probably because they fail to account for factors such as heterogeneity in both tissue composition and blood perfusion and non-capillary exchange mechanisms. The modelling of safe decompression procedures is further complicated by incomplete understanding of the processes that determine bubble formation. Moreover, any formation of bubbles during decompression alters subsequent nitrogen kinetics. Although these factors mandate complex resolutions to account for the interaction between dissolved nitrogen kinetics and bubble formation and growth, most decompression schedules are based on relatively simple perfusion-limited lumped compartment models of blood: tissue nitrogen exchange. Not surprisingly, all models inevitably require empirical adjustment based on outcomes in the field. Improvements in the predictive power of decompression calculations are being achieved using probabilistic bubble models, but divers will always be subject to the possibility of developing DCS despite adherence to prescribed limits.

Algorithms↗
PubMed2001

Ocular tear film bubble counts after recreational compressed air diving.

Other authors have demonstrated an increase in tear film bubble counts following dry, compressed air dives. We examined the lower tear film meniscus for the presence of bubbles in 42 divers after compressed air dives on a single day and in 11 divers undergoing repetitive, multi-day diving exposures over 5 days. After diving, bubble counts increased significantly (P < 0.01) from predive values. From a predive median (inter-quartile range) of 0 (0-0.33) bubbles/eye, single-day divers reached a maximum bubble count at 48 h after diving of 1 (0-2.25) bubbles/eye. Similarly, from a predive count of 0.33 (0-1) bubbles/eye, multi-day divers had increased bubble counts from 24 h following their first dive until 24 h following their final dive when counts were 1.67 (0.92-3.08) bubbles/eye. Bubble counts were not significantly correlated with inert gas load, body mass index, age, or diving experience. We confirm that tear film bubble counts are raised after wet compressed air diving as previously described following dry diving.

Adult↗
PubMed2000

In vivo manipulation and continuous measurement of muscle blood flow with venous effluent sampling.

1. An acute in vivo hindlimb skeletal muscle preparation was developed in anaesthetized sheep in order to facilitate studies of the effects of altered blood flow states on drug kinetics in skeletal muscle. 2. A continuous index of blood flow was recorded via ultrasonic Doppler probes on the femoral artery and vein. Skeletal muscle effluent blood was sampled via a catheter in the femoral vein proximal to the probe. Low- and high-blood flow states were achieved by direct femoral artery infusion of adrenaline (0.002-0.006 mg/min) or magnesium (0.4-1 mmol/min), which produced mean (+/-SD) stable flow states of 25+/-12 and 185+/-56% (both n = 5) of baseline, respectively. The correlation coefficients between arterial and venous Doppler frequency shifts in five sheep during and after adrenaline infusion were 0.96 (indicating these vessels probably supplied and drained common tissue). 3. The venous Doppler frequency shifts were calibrated against timed collections of the femoral vein outflow to provide estimates of the low and normal blood flow states (mean flows of 2.8+/-1.7 and 9.3+/-5.7mL/100 g per min; both n = 3) and against an indirect Kety-Schmidt method during low- and high-blood flow states (mean flows of 2.2+/-1.3 and 18.2+/-7.0 mL/100 g per min; both n = 5). There was a generally good agreement between the two methods. 4. The tissue was neither hypoxic nor acidotic in the low- or high-flow states and altering the flow produced no change in muscle oxygen consumption, suggesting the flow changes were largely due to changes in resistance vessel tone. 5. Postmortem femoral artery dye injection and dissection of stained tissues showed the artery supplied 657+/-96 g (n = 5) of skeletal muscle and 42+/-20 g (n = 5) of other tissues. 6. It is concluded that the method is suitable for sampling predominantly muscle effluent blood at low- or high-blood flow states according to experimental requirements.

Animals↗
PubMed2000

The effect of altered cerebral blood flow on the cerebral kinetics of thiopental and propofol in sheep.

BACKGROUND: Thiopental and propofol are highly lipid-soluble, and their entry into the brain often is assumed to be limited by cerebral blood flow rather than by a diffusion barrier. However, there is little direct experimental evidence for this assumption. METHODS: The cerebral kinetics of thiopental and propofol were examined over a range of cerebral blood flows using five and six chronically instrumented sheep, respectively. Using anesthesia (2.0% halothane), three steady state levels of cerebral blood flow (low, medium, and high) were achieved in random order by altering arterial carbon dioxide tension. For each flow state, 250 mg thiopental or 100 mg propofol was infused intravenously over 2 min. To quantify cerebral kinetics, arterial and sagittal sinus blood was sampled rapidly for 20 min from the start of the infusion, and 1.5 h was allowed between consecutive infusions. Various models of cerebral kinetics were examined for their ability to account for the data. RESULTS: The mean baseline cerebral blood flows for the "high" flow state were over threefold greater than those for the low. For the high-flow state the normalized arteriovenous concentration difference across the brain was smaller than for the low-flow state, for both drugs. The data were better described by a model with partial membrane limitation than those with only flow limitation or dispersion. CONCLUSIONS: The cerebral kinetics of thiopental and propofol after bolus injection were dependent on cerebral blood flow, despite partial diffusion limitation. Higher flows produce higher peak cerebral concentrations.

Anesthetics, Intravenous↗
PubMed1999

Agreement between ultrasonic Doppler venous outflow and Kety and Schmidt estimates of cerebral blood flow.

1. The present study compares the indirect Fick nitrous oxide equilibration method of Kety and Schmidt for cerebral blood flow (CBF) estimation with a direct ultrasonic Doppler index of venous outflow. 2. Cerebral blood flow was determined simultaneously by the direct measurement of sagittal sinus blood velocity and the indirect Kety and Schmidt method in five anaesthetized sheep during high and low steady states of CBF. High- and low-flow states were achieved by altering ventilation to produce hypercarbia and hypocarbia, respectively. 3. Four different sets of calculations were used to make the Kety and Schmidt estimations: arterial-venous nitrous oxide concentration differences during uptake or elution of the indicator and with or without extrapolation of arterial-venous differences to infinity. 4. During 15 min nitrous oxide administration, apparent blood:tissue equilibration of nitrous oxide was rapid in some data sets and slow in others. 5. There were no significant differences in CBF estimates between any of the four Kety and Schmidt calculations or the direct ultrasonic Doppler venous outflow method; however, CBF estimates based on nitrous oxide uptake correlated more strongly with the direct method than estimates based on nitrous oxide elution. 6. In the high-flow state, CBF estimates based on nitrous oxide uptake, but not those based on elution, distinguished between rapid and slow blood:tissue equilibration of nitrous oxide. 7. This provides validation of the Doppler sheep brain venous outflow method against the widely used Kety and Schmidt method.

Animals↗
PubMed1999

The relationship between the myocardial kinetics of meperidine and its effect on myocardial contractility: model-independent analysis and optimal regional model.

The myocardial kinetics of meperidine and the relationship between these kinetics and the effect of meperidine on myocardial contractility (maximum positive rate of change of left ventricular pressure) were examined by analysis of previously published data collected in sheep after the i.v. injection of 100 mg of meperidine over 1 s. There was significant hysteresis between reductions in myocardial contractility and the arterial concentrations of meperidine, but not the coronary sinus blood (effluent from the heart) or calculated myocardial concentrations. The peak reduction in contractility occurred after the peak arterial concentration, at the time of the peak myocardial concentration, but before the peak coronary sinus concentration, suggesting that the site of drug action in the heart was not in equilibrium with either arterial blood or effluent blood from the heart. The most appropriate form of a dynamic model (a linear model with a threshold) was determined, without the need to assume a kinetic model, by directly fitting the observed reductions in myocardial contractility to the calculated myocardial concentrations. To determine the optimal kinetic and combined kinetic-dynamic models, a variety of one-, two-, and three-compartment models of the myocardium were fitted to the coronary sinus concentrations by using hybrid modeling. These included "tank in series" models that accounted well for drug dispersion and "peripheral compartment" models that accounted well for deep distribution. The most appropriate model was a "compilation" model, which incorporated features of both these extremes and was a better fit to the observed data than either a traditional single flow-limited compartment or a traditional membrane-limited model.

Algorithms↗
PubMed1998

Diffusion-limited, but not perfusion-limited, compartmental models describe cerebral nitrous oxide kinetics at high and low cerebral blood flows.

This study aimed to evaluate the relative importance of diffusion-limited vs. perfusion-limited mechanisms in compartmental models of blood-tissue inert gas exchange in the brain. Nitrous oxide concentrations in arterial and brain efferent blood were determined using gas chromatographic analysis during and after 15 min of nitrous oxide inhalation, at separate low and high steady states of cerebral blood flow (CBF) in five sheep under halothane anesthesia. Parameters and model selection criteria of various perfusion- or diffusion-limited structural models of the brain were estimated by simultaneous fitting of the models to the mean observed brain effluent nitrous oxide concentration for both blood flow states. Perfusion-limited models returned precise, credible estimates of apparent brain volume but fit the low CBF data poorly. Diffusion-limited models provided better overall fit of the data, which was best described by exchange of nitrous oxide between a perfusion-limited brain compartment and an unperfused compartment. In individual animals, during the low CBF state, nitrous oxide kinetics displayed either fast, perfusion-limited behavior or slow, diffusion-limited behavior. This variability was exemplified in the different parameter estimates of the diffusion limited models fitted to the individual animal data sets. Results suggest that a diffusion limitation contributes to cerebral nitrous oxide kinetics.

Anesthetics, Inhalation↗
PubMed1997

Mechanism of adenosine accumulation in the hippocampal slice during energy deprivation.

The mechanism by which adenosine accumulates in the hippocampal slice during energy deprivation was investigated by examining the adenosine A1 receptor mediated depression of synaptically evoked field potentials in the CA1 area. Blocking of the mitochondrial electron transport chain with 200 microM sodium cyanide or mitochondrial uncoupling with 50 microM 2,4-dinitrophenol both produced a rapid depression of synaptic transmission that was antagonised by 1 microM 8-cyclopentyl-1, 3-dimethylxanthine, an adenosine A1 receptor antagonist. Cellular ATPase inhibition or elevation of cytosolic phosphocreatine failed to alter the 2,4-dinitrophenol induced depression of synaptic transmission. Attempts to block mitochondrial ATP synthesis with 3 microM oligomycin or 75 microM atractyloside did not cause depression of synaptic transmission. 100 microM iodotubercidin, an adenosine kinase inhibitor, alone produced a depression of synaptic transmission that was completely reversed by 1 microM 8-cyclopentyl-1,3-dimethylxanthine; however, a simultaneous or independent episode of hypoxia surmounted the adenosine A1 receptor antagonism and produced approximately 50% depression of synaptic transmission. Depression of synaptic transmission by hypoxia, cyanide or 2,4-dinitrophenol is a result of rapid adenosine accumulation and activation of extracellular adenosine A1 receptors. Although this early depression of synaptic transmission is a consequence of inhibition of normal mitochondrial function, it is not a result of depletion of cytosolic ATP, since attempts to preserve ATP did not maintain synaptic transmission during mitochondrial poisoning, and inhibitors of oxidative phosphorylation did not produce synaptic depression.

2,4-Dinitrophenol↗
PubMed1995

The (S)-enantiomer of 2-hydroxysaclofen is the active GABAB receptor antagonist in central and peripheral preparations.

In the guinea-pig isolated ileum, (RS)-(+/-)-baclofen induced a depression of cholinergic twitch contractions, reversibly and competitively antagonised by (S)-2-hydroxysaclofen (pA2 = 5.2 +/- 0.2), but not by (R)-2-hyroxysaclofen. The depression of excitatory field potentials by baclofen ( 5 mu M) in rat CA1 hippocampal slices was antagonised by (S)-2-hydroxysaclofen (100 mu m) (pA2 = 4.3), whilst in rat neocortex, (S)-2-hyroxysaclofen (50-500 mu M) antagonised the baclofen (10 mu M)-induced suppression of spontaneous discharges, the (R)-enantiomer being inactive. These results show that (S)-2-hydroxysaclofen is the active antagonist at central and peripheral GABAB receptors.

Animals↗
PubMed1995

Hyperexcitability in CA1 of the rat hippocampal slice following hypoxia or adenosine.

Participation of adenosine receptors in the depression of synaptic transmission during hypoxia, and the production of multiple populations spikes in the pyramidal neurons following hypoxia, has been investigated in the CA1 area of the rat hippocampal slice. A method is presented for analysing such hyperexcitability, using input/output curves of the second population spike. This method provides evidence that rebound hyperexcitability following hypoxia or prolonged adenosine-mediated inhibition results from an increase in excitability of the CA1 pyramidal neurons rather than from an increase in excitatory neurotransmitter release. Hypoxia-induced depression of the synaptic components of evoked field potentials was blocked in a concentration dependent manner by the selective A1 receptor antagonist 8-cyclopentyltheophylline (8-CPT), demonstrating extracellular accumulation of adenosine during hypoxia. Upon reoxygenation of slices following 30 min hypoxia, multiple population spikes were evoked by a single orthodromic stimulus in slices that exhibited only a single population spike prior to hypoxia. Such post-hypoxic hyperexcitability was not prevented by superfusion of slices with 8-CPT during hypoxia. Depression of synaptic transmission by 30 min superfusion of slices with 50 microM adenosine was also followed, upon washout, by the appearance of multiple population spikes. However, such hyperexcitability could not be produced by superfusion with adenosine analogues selective for A1 receptors, cyclopentyladenosine, selective for A2a receptors, 2-p-(2-carboxyethyl)phenetheylamino-5'-ethylcarboxamidoadenosine (CGS 21680), or active at A2a and A2b receptors, N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine, suggesting that adenosine receptors other than the A1, A2a or A2b subtypes are involved in its generation.

Adenosine↗