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Biomedical subjects

C A Dawson

Publications and source records attributed to C A Dawson.

At least 109 records · Page 6Linked to original sources
PubMed1989

On the estimation of pulmonary capillary pressure from arterial occlusion.

We have attempted to evaluate some approaches for estimating pulmonary capillary pressure from the transient pressure data obtained from the tip of the Swanz-Ganz catheter after inflation of the balloon. To this end experiments were carried out in anesthetized dogs in which pulmonary vasoconstriction was induced by infusion of histamine, serotonin, or norepinephrine or by hypoxia. In a group of closed chest dogs, the time course for the fall in the catheter tip pressure toward the wedge pressure was different for the different vasoconstrictors. For example, during histamine infusion the fall in pressure was slow, whereas during serotonin infusion it was rapid. To evaluate the information in the decay curves, a group of dogs was studied with open thorax to permit the simultaneous occlusion of both the artery and vein of one lung lobe (double occlusion) as well as occlusion of the lobar artery alone (arterial occlusion). The pattern of response to the various vasoconstrictors observed with lobar arterial occlusion was similar in these animals to the closed chest animals. The equilibrium pressure after double occlusion (the double occlusion pressure), expressed as a fraction of the mean arterial-venous pressure difference before occlusion, was correlated with the mean decay time of the arterial pressure curve after arterial occlusion. We also found significant correlations between the double occlusion pressure and the estimates of capillary pressure based on model interpretations of the pressure decay curve after arterial occlusion. However, there was wide scatter in the individual comparisons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Evaluation of endothelial injury in the human lung.

The pulmonary endothelium plays a crucial role in the normal function of the lungs. Damage to the pulmonary endothelium is thought to be a primary event leading to deficits in pulmonary function in diverse forms of lung injury, but it is difficult to detect until these secondary deficits are manifest. Indicator dilution methods are practical for evaluation of endothelial function in patients. Interpretation of the information contained in the data is potentially complex, and specificity may be improved by using multiple indicators, each of which interacts with the endothelium in a different way. The general clinical utility of the methods is not yet established. However, encouraging experimental results, clinical studies, and improved technologies suggest that the methods have the potential to be of significant diagnostic and prognostic value.

Capillary Permeability↗
PubMed1989

First-pass uptake of verapamil, diazepam, and thiopental in the human lung.

The first-pass uptake of verapamil, diazepam, and thiopental in the human lung was determined using multiple-indicator dilution techniques. These three drugs represent lipid-soluble agents that differ in their ionic characteristics at physiological pH. Verapamil, a basic lipophilic amine, underwent significant uptake, with 50% of the drug accumulating in lung tissue during the first pass. With diazepam, a nonbasic lipophilic amine, there was 30% uptake during the first pass through the human lung--significantly less than that observed with verapamil. With thiopental, an acidic lipophilic barbiturate, only 14% of the injected drug accumulated in the lung during the first pass. Taken together, these data are consistent with observations from animal studies, which indicate that extensive pulmonary uptake is greater with basic amine drugs that are moderately to highly lipid-soluble. Also, the relatively high first-pass uptake of verapamil in the human lung suggests a quantitatively significant role of this nonrespiratory function of the lung in the early pharmacokinetics of intravenous verapamil.

Adult↗
PubMed1988

Distributions of vascular volume and compliance in the lung.

The ether- and dye-dilution methods were used to estimate the arterial, capillary, and venous volumes and compliances in isolated dog lung lobes. In the range of arterial pressure from approximately 7 to 14.5 Torr and venous pressure of 1.4 to 10.8 Torr, the total lobar blood volume ranged from approximately 2 to approximately 2.6 ml/kg body wt. About 19% of the lobar vascular volume was in the arteries, approximately 59% was in the capillaries, and approximately 22% was in the veins. The lobar vascular compliance was approximately 0.065 ml.Torr-1.kg body wt-1 with an arterial-capillary-venous distribution of approximately 30:49:21. These results suggest that the largest fractions of the intralobar blood volume and compliance are in the capillary bed. The segmental compliances along with outflow occlusion data were used to place lower and upper bounds on the arterial, capillary, and venous resistances. These bounds were 13.6 and 61.4% of the total vascular resistance for the arteries, 0 and 59.4% for the capillaries, and 5.5 and 64.9% for the veins, respectively. These bounds are rather broad, but they help to put the information content of the occlusion data under the conditions of these experiments into perspective.

Animals↗
PubMed1988

Distributions of vascular pressure and resistance in the lung.

The low-viscosity bolus method was used to determine the longitudinal distributions of vascular resistance and intravascular pressure with respect to cumulative vascular volume from the lobar artery to the lobar vein in isolated dog lung lobes near functional residual capacity under zone 3 conditions. We found that the resistance distribution had two modes, a larger one upstream and a smaller one downstream from a local minimum. Over the range of vascular pressures studied the total vascular resistance decreased and the vascular volume increased with increasing vascular pressure. However, the shape of the normalized resistance distribution was independent of vascular pressure. Comparisons of the resistance distributions with the distributions of arterial, capillary, and venous volumes suggest that the modes represent regions of relatively high resistance proximal and distal to the capillary bed. These results are consistent with the concept that within the lobar vascular bed the highest resistance per unit blood volume is in the smallest arteries and veins, as suggested by morphometric data from other sources.

Animals↗
PubMed1987

Kinetics of uptake and metabolism by endothelial cell from indicator dilution data.

Certain substrates are rapidly taken up and/or metabolized by pulmonary endothelial cells in a saturable process. When such a substrate and a reference indicator are included in a bolus which is injected into the blood flowing into the lung, the extraction ratio, E(t), curves measured in the pulmonary venous outflow are asymmetric with respect to the reference indicator curve. If a sufficient quantity of substrate is included in the bolus, the extraction curves are concave upward. The shapes of the E(t) curves contain information regarding the chemical-physical processes which govern the fate of the substrate during its single passage through the lung. To interpret the shapes, computer simulations are used to illustrate separately the effects of the uptake of substrate into the cell, the returning flux of the substrate from the cell, the saturation phenomena of the extraction process, and the perfusion heterogeneity of the capillaries. Lastly, a simple analytical method for estimating the organ kinetic parameters of the extraction process is presented.

Animals↗
PubMed1987

Kinetics of serotonin uptake in the intact lung.

The pulmonary endothelium is capable of removing and metabolizing serotonin (5HT) carried in the venous blood. Thus the lungs can influence the arterial concentrations of 5HT. In addition, there is evidence that changes in the lung uptake of 5HT might portend more serious endothelial damage wherein the barrier function of the endothelium is compromised. This has been a stimulus for finding methods for evaluating these endothelial functions. These methods must be able to distinguish changes in whole organ function which result from changes in perfusion (e.g., cardiac output, redistribution of flow, etc.) from those resulting from changes in the function of the endothelial cells. When a bolus containing radio-labeled 5HT and an unmetabolizable indicator which is confined to the vascular space is injected into the pulmonary artery, the pulmonary venous or systemic arterial concentration curves contain information about both the convective transport and endothelial cell process involved. Some of this information can be interpreted quantitatively using a simple mathematical model.

Animals↗
PubMed1987

First pass uptake of fentanyl, meperidine, and morphine in the human lung.

The first pass uptake of fentanyl, meperidine, and morphine in human lung was studied in patients using a double indicator dilution technique. A bolus containing one of the drugs and indocyanine green dye (ICG) was rapidly injected into the central venous catheter of patients prior to anesthesia for surgery. Sequential arterial blood samples were collected at 1-s intervals for 45 s after injection. The total amount of drug taken up by the lung during the first pass and the instantaneous extraction of drug at each time point during the first pass were calculated from the differences in the arterial blood concentration versus time curves of the nondiffusible indicator (ICG) and the drug. The total uptake (mean +/- SE) during the first pass through the human lung for fentanyl and meperidine was 75.2 +/- 3.2% and 64.7 +/- 7.8% of the injected dose, respectively. The pulmonary uptake of morphine was very small, with 96.5 +/- 7.1% of the injected dose recovered in arterial blood after the first pass through the lung. The arterial blood concentration of drug and dye versus time showed a slight delay of the fentanyl and meperidine peaks compared to ICG. It was also observed that greater than 90% of these drugs were extracted from the blood in the early part of the first pass, but the extraction decreased with time during the first pass through the lung. These findings indicate that some of the drug taken up by the lung can diffuse back out into the blood.2+off

Aged↗
PubMed1987

Evaluation of Mast-ID 15 system for identifying Enterobacteriaceae, some Vibrionaceae, and Acinetobacter.

Six hundred and twenty one strains (555 Enterobacteriaceae, 46 Vibrionaceae, and 20 Acinetobacter) were examined in the Mast system. The results were consulted in the code book supplied by the manufacturer and those not listed were processed through the manufacturer's full database held on an Apricot microcomputer in our laboratory. The proportion of strains correctly identified was 88%, with 9% not identified, and 3% incorrectly identified.

Acinetobacter↗
PubMed1987

Effects of gas composition and pH on kinetics of lung angiotensin-converting enzyme.

Given the pH dependence of enzymes in general and the potential importance of a blood and alveolar gas composition dependency on the interpretation of changes in the hydrolysis of angiotensin-converting enzyme (ACE) substrates by pulmonary endothelial ACE, we examined the influence of Pco2 and Po2 on the hydrolysis of a synthetic ACE substrate (benzoyl-phenylalanyl-alanyl-proline, BPAP) on passage through isolated rabbit lungs. Perfusate pH values of about 7.1, 7.4, and 7.9 were obtained by ventilating the lungs with gas containing different CO2 concentrations and Po2 values of approximately 110 and approximately 10 Torr were obtained by varying the concentration of O2 in the ventilating gas mixture. In the range studied neither acidosis nor alkalosis produced any significant changes in BPAP hydrolysis or in the kinetic parameters, Vmax and Km, for the hydrolysis process. On the other hand, a reduction in BPAP hydrolysis was detected when the Po2 was reduced from 110 to 10 Torr. The Vmax for BPAP hydrolysis by the lung was inversely correlated with the magnitude of the hypoxic vasoconstriction that occurred, suggesting that the reduced BPAP hydrolysis with hypoxia was due to the loss of perfused surface area due to the vasoconstriction. The results suggest that correlations between Pco2 and/or pH and whole-lung ACE activity that might occur in diseased lungs do not imply causalty. The hemodynamic consequences of changing Po2 (i.e., hypoxic vasoconstriction) may alter whole-organ ACE activity in the sense of changing the perfused surface area (i.e., the amount of ACE in contact with flowing perfusate).

Animals↗
PubMed1987

Pulmonary arterial transit times.

To begin to characterize the pulmonary arterial transport function we rapidly injected a bolus containing a radiopaque dye and a fluorescence dye into the right atrium of anesthetized dogs. The concentrations of the dye indicators were measured in the main pulmonary artery (fluoroscopically) and in a subpleural pulmonary arteriole (by fluorescence microscopy). The resulting concentration vs. time curves were subjected to numerical deconvolution and moment analysis to determine how the bolus was dispersed as it traveled through the arteriole stream tube from the main pulmonary artery to the arteriole. The mean transit time and standard deviation of the transport function from the main pulmonary artery to the arterioles studied averaged 1.94 and 1.23 s, respectively, and the relative dispersion (ratio of standard deviation to mean transit time) was approximately 64%. This relative dispersion is at least as large as those reported for the whole dog lung, indicating that relative to their respective mean transit times the dispersion upstream from the arterioles is comparable to that taking place in capillaries and/or veins. The standard deviations of the transport functions were proportional to their mean transit times. Thus the relative dispersion from the main pulmonary artery to the various arterioles studied was fairly consistent. However, there were variations in mean transit time even between closely adjacent arterioles, suggesting that variations in mean transit times between arteriole stream tubes also contribute to the dispersion in the pulmonary arterial tree.

Animals↗
PubMed1987

Alveolar vessel behavior in the zone 2 lung inferred from indicator-dilution data.

To gain insight into the changes occurring in alveolar vessels when alveolar pressure exceeds venous pressure at the downstream end of the alveolar vessels (zone 2), we compared the uptake of serotonin and the extravascular volume accessible to 3HOH (Qev) under zone 2 and 3 conditions in isolated dog lung lobes. We also examined the influence of occluding some of the small pulmonary arteries with 58- to 548-micron-diam beads on the serotonin uptake and Qev. We found that, with the bead embolization, both the serotonin uptake and the Qev were reduced, whereas the change from zone 3 to 2 reduced serotonin uptake but did not change Qev. A plausible explanation for these observations is that the beads occluded vessels that were relatively large compared with those in which significant transvascular 3HOH exchange and serotonin uptake take place. Perfusion ceased in the collection of capillaries normally served by the obstructed arteries. Thus the extravascular water and the serotonin uptake sites downstream from the obstructions were not accessible to the indicators during the short time interval of the indicator passage through the lung. On the other hand, the change from zone 3 to zone 2 resulted in the collapse of small individual capillary segments within the alveolar vessel bed. Since the serotonin does not readily diffuse from the vessels through the tissue, it could not reach the endothelial cells of the collapsed capillaries. However, since the distances for diffusion between collapsed capillaries and neighboring perfused capillaries were small, the more highly diffusible 3HOH had access to the same Qev under both zone 2 and 3 conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1986

A revised probability matrix for the identification of gram-negative, aerobic, rod-shaped, fermentative bacteria.

The results of the identification of 933 strains of Gram-negative, aerobic, rod-shaped, fermentative bacteria (Enterobacteriaceae, Pasteurellaceae, Vibrionaceae) by a probabilistic method, in a computer, are given. The identification rate on the matrix was 89.2%. Many of the strains were atypical and had caused difficulty in identification in medical diagnostic laboratories. The results are given for each taxon by genus and species.

Bacteria↗
PubMed1986

The identification of Bacteroides ureolyticus from patients with non-gonococcal urethritis by conventional biochemical tests and by DNA and protein analyses.

Twenty-seven strains of gram-negative anaerobic bacteria isolated from patients with non-gonococcal urethritis (NGU-associated strains) were compared with reference strains of Bacteroides ureolyticus and representatives of other species of Bacteroides and Fusobacterium. Conventional biochemical tests, electrophoretic (PAGE) protein profiles and DNA base compositions of 29.5 +/- 1.2 mol% G + C indicated striking similarities between the NGU-associated strains and B. ureolyticus. Three of the reference strains previously assigned to that species were atypical in some respects as was one of the strains from urethritis and one strain, NCTC 10939, was incorrectly classified as B. ureolyticus. Casein hydrolysis by B. ureolyticus was the principal test difference between the two sets of strains. DNA-DNA hybridisation results of greater than or equal to 72% at optimum temperature conditions provided further evidence of the close relationship between B. ureolyticus and the NGU-associated strains and we conclude that these organisms should be identified as B. ureolyticus. There was insufficient evidence for recognising subspecies or biotypes within this revised concept of B. ureolyticus although several types (PAGE-type I, 17 strains; type II, 6 strains; type III, 3 strains) were detected which might provide the basis for future studies of hospital strains. The DNA base composition and hybridisation data indicated that B. ureolyticus was not related to other species of Bacteroides or Fusobacterium.

Bacterial Proteins↗
PubMed1986

Effect of hypoxia and hypercapnia on ACE activity in the cerebral microcirculation of anesthetized dogs.

Angiotensin-converting enzyme (ACE) activity of the cerebral microcirculation of anesthetized dogs was measured from cerebral venous outflow curves after bolus injection of a synthetic ACE substrate, [3H]benzoyl-phenylalanyl-alanylproline ([3H]BPAP), into a common carotid artery. Cerebral BPAP metabolism was quantified by measuring the concentration of [3H]benzoyl-phenylalanine (the product of BPAP hydrolysis by ACE) in blood samples from the sagittal sinus after occlusion of the lateral sinuses with bone wax. Instantaneous BPAP metabolism in each sample increased as a function of time after injection, suggestive of perfusion heterogeneity, and averaged 59 +/- 4% (n = 8) over a single pass during normoxia and normocapnia. The ratio of Vmax (the maximal rate of cerebral BPAP metabolism) to Km (the concentration at Vmax/2), was calculated from instantaneous outflow curves using a model based on first-order kinetics. Increases in cerebral blood flow during either hypoxia or hypercapnia significantly reduced BPAP metabolism to 33 +/- 3 (n = 7) and 24 +/- 3% (n = 5), respectively; however, Vmax/Km of ACE activity (0.19 +/- 0.03 ml/s) was not affected by either condition. The lack of change in apparent kinetics of ACE activity (i.e., in Vmax/Km) during hypoxia or hypercapnia suggests that recruitment of cerebral capillaries was not a quantitatively significant factor in controlling BPAP metabolism with this degree of either hypoxia or hypercapnia.

Anesthesia↗
PubMed1986

Location and mechanisms of pulmonary vascular volume changes.

We examined the influence of changing outflow pressure, P out, on the vascular and extravascular volumes (QV and QEV, respectively, as measured by indicator dilution) and on the outflow occlusion pressures in isolated dog lung lobes perfused with constant flow. Changing P out had a substantial effect on QV, but not on QEV, whether P out was less than or greater than alveolar pressure, PA. Since QEV did not change with QV, recruitment of previously unperfused vessels did not appear to contribute substantially to the increases in QV when P out was increased. The rapid jump in P out immediately following outflow occlusion was virtually independent of the difference between PA and P out suggesting that the alveolar vessels were an important volume storage site when P out was low relative to PA. We conclude that, over a certain range of pressures, alveolar vessel volume can be controlled by venous pressure even when the change in venous pressure has little effect on arterial pressure (zone 2). Further, we conclude that in zone 3 and within the transition from zone 2 to zone 3 increases in the intralobar blood volume occurring within the alveolar vessels may not require recruitment in the sense of opening of previously unperfused vessels.

Animals↗
PubMed1986

Pulmonary vascular compliance and viscoelasticity.

When dog lung lobes were perfused at constant arterial inflow rate, occlusion of the venous outflow (VO) produced a rapid jump in venous pressure (Pv) followed by a slower rise in both arterial pressure (Pa) and Pv. During the slow rise Pa(t) and Pv(t) tended to converge and become concave upward as the volume of blood in the lungs increased. We compared the dynamic vascular volume vs. pressure curves obtained after VO with the static volume vs. pressure curves obtained by dye dilution. The slope of the static curve (the static compliance, Cst) was always larger than the slope of the dynamic curve (the dynamic compliance, Cdyn). In addition, the Cdyn decreased with increasing blood flow rate. When venous occlusion (VO) was followed after a short time interval by arterial occlusion (AO) such that the lobe was isovolumic, both Pa and Pv fell with time to a level that was below either pressure at the instant of AO. In an attempt to explain these observations a compartmental model was constructed in which the hemodynamic resistance and vascular compliance were volume dependent and the vessel walls were viscoelastic. These features of the model could account for the convergence and upward concavity of the Pa and Pv curves after VO and the pressure relaxation in the isovolumic state after AO, respectively. According to the model analysis, the difference between Cst and Cdyn and the flow dependence of Cdyn are due to wall viscosity and volume dependence of compliance, respectively. Model analysis also suggested ways of evaluating changes in the viscoelasticity of the lobar vascular bed. Hypoxic vasoconstriction that increased total vascular resistance also decreased Cst and Cdyn and appeared to increase the vessel wall viscosity.

Animals↗