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Biomedical subjects

C A Dawson

Publications and source records attributed to C A Dawson.

At least 127 records · Page 7Linked to original sources
PubMed1986

Cat lung hemodynamics: comparison of experimental results and model predictions.

Commonly, attempts have been made to learn about the structure and function of the pulmonary vascular bed from measurements of arterial and venous pressures and blood flow rate under steady-state conditions (e.g., from pressure vs. flow data) or dynamic conditions (e.g., from vascular occlusion data). Zhuang et al. (J. Appl. Physiol. 55: 1341-1348, 1983) have presented a detailed model of steady-state cat lung hemodynamics based on direct measurements of anatomical and elasticity data. This model provides an opportunity to better understand the information content of the hemodynamic data. Therefore, in the present study we carried out a series of steady-state and dynamic experiments on isolated cat lungs. We then compared the results with those predicted by the model. We found that the model provided a good fit to the steady-state data. However, to fit the dynamic data, some modifications were necessary to account for the viscous behavior of the vessel walls and to move the first moment of the distribution of vascular resistance toward the arterial end of the vascular bed relative to that of the distribution of vascular compliance. Due to the sensitivity of the vascular resistance to small changes in vessel diameters and branching ratio, the modifications in morphometry represent small changes in morphometric data and are probably within the range of uncertainty in such data. The modifications had little effect on the steady-state model simulations but substantially improved the dynamic model simulations, suggesting that the dynamic data are quite sensitive to small changes in the relative distributions of vessel diameters and elasticity.

Animals↗
PubMed1985

Limits on the continuous distribution of pulmonary vascular resistance versus compliance from outflow occlusion.

Rapid occlusion of the venous outflow from a lung lobe perfused with constant flow causes the arterial and venous pressure to increase with time. Pressure values obtained by linear extrapolation of the nearly linear portions of the resulting arterial and venous pressure versus time curves back to the instant of occlusion provide data which can be used to place limits on the actual unknown distribution of resistance versus compliance. This has been proven deductively for the case of compartmental models having a small number of resistances and compliances. For compartmental models having a large number of resistances and compliances approaching a continuous distribution, an inductive approach was used in which a large number of simulations indicated that the actual continuous distribution is confined by the experimental data to the same limits as those for the small number of resistances and compliances.

Animals↗
PubMed1985

A probability matrix for the identification of vibrios.

A probability matrix for computer-assisted identification of vibrios has been constructed, based on the API 20E system. Data were gathered from 173 strains representing 31 taxa of vibrios and related organisms, from a variety of sources. The matrix was tested internally by four statistical programs. Program OVERMAT tested the separation and program MOSTTYP the discretion and homogeneity of the taxa. Most of the taxa were satisfactory but a few were less so; reasons for this are discussed. Program CHARSEP and program DIACHAR tested the separation and diagnostic values, respectively, of the characters used. The overall test error was 4.5%. The matrix was assessed externally by its performance in the identification of vibrio-like strains isolated from freshwater. Of 243 wild strains, 79.4% were identified with ten taxa, with a Willcox score of greater than or equal to 0.99.

Computers↗
PubMed1985

Misuse and interlaboratory test reproducibility of API 20E system.

One hundred strains were referred to us for identification because they apparently could not be identified satisfactorily with the API 20E system (appareils et procédés d'identification). The inability to identify 31 strains was due primarily to failure to follow the manufacturer's instructions. Twenty six further strains were found to have been correctly identified by the sender's own API 20E results, so that only the remaining 43 strains definitely fell into the category for which our identification service was intended. Eighteen of the 43 strains not identified by the sender were identified by us using the API 20E system, and several possible reasons are given to explain the differences in these results. The remaining 25 strains either could not be identified by us on the API 20E system or, in the case of 13, they could not be identified by our conventional system and therefore no comparison could be made. The average interlaboratory probability of errors for the API 20E tests was 6.1%.

Bacteriological Techniques↗
PubMed1985

Influence of pulmonary embolism on absorption of inhaled iodide-125.

To evaluate the influence of embolus size on the absorption of 125I- deposited on the bronchoalveolar surface, we exposed isolated perfused rabbit lungs to an aerosol containing 125I- for 5 min. We monitored the blood radioactivity for the subsequent 2 h. Several groups of lungs were studied, including those in which blood flow was varied and those in which enough glass beads ranging in size from 58 to 548 micron were injected into the pulmonary artery to approximately double the vascular resistance. The results indicated that under control conditions approximately 94% of the 125I- deposited on the intrapulmonary bronchoalveolar surface was able to reach the pulmonary circulation during the 2-h perfusion period, and the bronchoalveolar surface was sufficiently perfused so that absorption was limited by the rate of diffusion into the blood rather than the rate of blood flow. In the absence of embolization, the initial absorption rate was approximately 10.4%/min regardless of the total flow rate. The 58-micron beads reduced the rate to approximately 7.5%/min, whereas the beads greater than or equal to 194 micron in diameter reduced the rate to approximately 4.5%/min. Thus the effect of the embolization on the absorption rate was directly related to the bead diameter, even though the number of beads injected was adjusted to produce about the same increase in vascular resistance.

Absorption↗
PubMed1985

Lung damage and pulmonary uptake of serotonin in intact dogs.

We examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of [3H]serotonin and the extravascular volume accessible to [14C]antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.

Animals↗
PubMed1985

Hypoxia-induced activation in small isolated pulmonary arteries from the cat.

Effects of hypoxia on force development and membrane potential were studied in isolated small (less than 300 microns diam) and large (greater than 500 microns diam) pulmonary arteries from cats. There was a consistent and reproducible hypoxic constrictor response in small pulmonary arteries that began at PO2 values between 350 and 300 Torr and reached a maximum at PO2 between 50 and 30 Torr. In the small artery smooth muscle cell the membrane potential, which was -51 +/- 1.4 mV at a PO2 of 400 Torr, was depolarized to -37 +/- 2 mV at a PO2 of 50 Torr. In contrast, larger arteries did not exhibit significant hypoxic constriction or depolarization upon exposure to low PO2. Constriction in small arteries was not blocked by phentolamine. Treatment with a low dose of indomethacin (10(-9) M) augmented the response; however, a larger dose of indomethacin (10(-3) M) blocked the constriction to hypoxia but not to 30 mM KCl. Depolarization during hypoxia was not blocked by ouabain. Results of this study suggest that the hypoxic response of these isolated small pulmonary vessels may be like that seen in the intact lung. Furthermore, these data suggest that hypoxic vasoconstriction may be mediated by electrical events occurring at the pulmonary arterial muscle cell membrane either directly or via mediators released from the vessel wall.

Animals↗
PubMed1985

Isolated total lung perfusion as a means to deliver organ-specific chemotherapy: long-term studies in animals.

The objectives of this study were to develop a surgical procedure that would allow for bilateral isolated lung perfusion in vivo as a means of delivering organ-specific chemotherapy and to evaluate the influence of the procedure on certain pulmonary physiologic parameters. The sterile surgical procedure that was carried out in dogs involved the setting up of two separate perfusion circuits. Once standard systemic cardiopulmonary bypass was established, a second circuit was devised to perfuse the lungs by placing an inflow cannula into the main pulmonary artery and collecting venous effluent in the left atrium. Cross-contamination between perfusion circuits was determined in acute studies with labeled plasma protein or red blood cells and was found to be in an acceptable range if the aorta was cross-clamped and the heart arrested. Only about 0.4 ml/min of pulmonary perfusate leaked into the systemic circulation, indicating that systemic toxicity should not be a major concern when chemotherapy agents are added to the pulmonary perfusate. Chronic studies demonstrated that hemodynamic parameters, lung water, pulmonary endothelial serotonin extraction, and histologic findings all showed minimal changes after 50 minutes of isolated lung perfusion. Five days after perfusion, lung dynamic compliance and peak serotonin extraction showed significant decreases. However, all of the measured parameters had returned toward baseline levels by the end of the 8-week postoperative study period. The procedure offers significant advantages over the previously described single lung perfusion and may provide a method of delivering immediate high-concentration adjuvant chemotherapy to coincide with resection of primary or metastatic lung tumors.

Animals↗
PubMed1984

A model of the vascular resistance and compliance distribution in a lung lobe.

The arterial and venous pressure curves obtained after occluding the venous outflow from a dog lung lobe perfused with constant flow contain information about the intralobar longitudinal distribution of vascular resistance (R) and compliance (C). To utilize this information, a lumped model consisting of four parallel C's separated by three serial R's was used. Solutions of the governing differential equations yield a nonlinear system of four algebraic equations in the seven unknowns and the measured data. Three of the equations form a linear subsystem in which the unknowns are the three R's and the coefficients are functions of the four C's. This is an underdetermined system, but when nonnegativity and boundedness constraints are adjoined, the solution set falls within a narrow band of distributions of cumulative R relative to cumulative C. The shape of this band changes when data are obtained from lobes influenced by various vasoactive stimuli revealing the changes in the longitudinal distribution of the vascular resistance relative to the vascular compliance.

Animals↗
PubMed1984

Influence of plasma protein on the inhibitory effects of indocyanine green and bromcresol green on pulmonary prostaglandin E1 extraction.

The purpose of this study was to examine the influence of plasma protein on the inhibitory effects of the anionic dyes indocyanine green and bromcresol green on prostaglandin E1 (PGE1) uptake by the lungs. Dog lung lobes were isolated and perfused with either autologous plasma or Krebs-Ringer bicarbonate solution (KRB) containing no protein but with dextran used as a colloid. PGE1 uptake was determined by injecting a bolus, containing radiolabelled PGE1 into the lobar artery and then analysing ethanolic extracts of the venous effluent for radioactivity in PGE1 and PGE1 metabolites by thin layer chromatography and scintillation counting. When the lobes were perfused with KRB, bromcresol green at an average initial concentration of 28.5 microM, reduced PGE1 by an average of 56%. When the lobes were perfused with plasma, similar concentrations of bromcresol green reduced the uptake by less than 2%. A similar result was obtained with indocyanine green, which at an average initial concentration of 17.5 microM reduced uptake by about 70% when the lobes were perfused with KRB, but when the lobes were perfused with plasma similar concentrations of the dye reduced uptake by less than 3.5%. The results suggest that plasma protein binding interferes with the inhibitory effects of these dyes on PGE1 uptake in the lungs.

Alprostadil↗
PubMed1984

Influence of embolism and imipramine on kinetics of serotonin uptake by dog lung.

We previously presented a model from which the kinetic parameters Km and Vmax for serotonin uptake by the lung can be obtained from multiple indicator-dilution data. The purpose of the present study was to determine whether experimentally induced changes in lung endothelial function would be revealed in the kinetic parameters calculated using the model. In experiments using isolated dog lung lobes, embolization with 550-microns glass beads was used to reduce the vascular volume and perfused surface area. Imipramine was used to inhibit the serotonin uptake mechanism. In addition, we studied the influence of the vasodilator papaverine, which in previous studies had been used to block the serotonin-induced vasoconstriction. Embolization, imipramine, and papaverine all significantly reduced percentage uptake of serotonin. The kinetic analysis revealed a significant decrease in the maximum serotonin uptake rate (Vmax) with all three experimental manipulations. In addition, imipramine significantly increased Km. The results indicate that the kinetic parameters obtained from the model do respond to transport inhibition and changes in endothelial surface area, further supporting their usefulness as indexes of endothelial function.

Animals↗
PubMed1984

Lung serotonin uptake kinetics from indicator-dilution and constant-infusion methods.

The kinetics of the pulmonary endothelial uptake of serotonin (5-HT) were evaluated in isolated dog lung lobes using three methods. In method A serotonin was infused at various constant rates to provide a range of capillary concentrations that included Km. The arterial and venous concentrations measured by high-performance liquid chromatography were then used to determine the effect of concentration on the rate of 5-HT uptake. In method B trace doses of 5-[3H]HT and a reference indicator (indocyanine green dye) were injected during each constant infusion of unlabeled 5-HT to provide a measure of unidirectional 5-HT uptake at each background concentration. In method C boluses containing different amounts of unlabeled 5-HT, along with the 5-[3H]HT and the dye, were injected such that each bolus resulted in a range of concentrations and provided a measure of the unidirectional uptake at each concentration. Each method provided the data needed to calculate the maximum uptake rate (Vmax) and the concentration at Vmax/2 (Km), assuming that the uptake kinetics can be represented by the Michaelis-Menten equation. However, the mathematical model underlying each method involved different assumptions about the returning flux of the 5-HT which entered the endothelial cell and the heterogeneity of vascular transit times. The results obtained, considered in light of the different assumptions involved, indicate that all three methods can provide reasonable estimates of the mass transfer kinetic constants if the constant infusions of 5-HT are of short duration and/or the boluses are adequately dispersed prior to reaching the capillary bed.

Animals↗
PubMed1984

Kinetics of serotonin uptake by the dog lung is pH independent in the physiological range.

Given the strong pH dependence of platelet serotonin uptake, the many similarities between platelet and pulmonary endothelial serotonin uptake and the potential importance of a pH dependence on the interpretation of changes in pulmonary endothelial serotonin uptake in diseased lungs, we examined the influence of pH on the kinetics of serotonin uptake in isolated dog lung lobes using a multiple indicator technique. A range of pH values from about 7.2 to 8.0 were obtained by ventilating the lobes with gas containing different concentrations of CO2. Over the pH range studied, no significant changes in serotonin uptake were observed, nor were significant changes detected in the kinetic parameters, Km and Vmax, for the uptake process. The lack of a significant pH effect represents a difference between platelet and lung endothelial serotonin uptake. It also indicates that correlations between PCO2 and serotonin uptake which might occur in diseased lungs do not imply causality.

Animals↗
PubMed1983

Model-free deconvolution techniques for estimating vascular transport functions.

In this paper we present two methods which can be used to numerically deconvolve indicator dilution curves to obtain vascular transport functions. In the first method, direct algebraic deconvolution is made stable and practical by the damped least squares method. The second method involves a time-shift of the output curve which is based on the first and second moments of the input and output curves. This method is stable, computationally simple and can provide reasonable estimates of the transport function.

Animals↗
PubMed1983

Influence of pulmonary vasoconstriction on lung water and perfusion heterogeneity.

To determine the influence of pulmonary vasoconstriction on lung tissue perfusion, we examined the effects of hypoxia, sympathetic nerve stimulation, and histamine on vascular resistance, blood, and extravascular volumes, weight, and the distribution of vascular transit times in dog left lower lung lobes perfused in situ. Hypoxia, sympathetic stimulation, and histamine increased pulmonary vascular resistance by 1.96, 1.42, and 2.02 times and increased the relative dispersion of the transit time distributions by 1.49, 1.30, and 1.71 times the control values, respectively. Hypoxia and sympathetic stimulation tended to decrease the blood volume accessible to indocyanine green dye and the lobe weight. On the other hand, histamine infusion, which also decreased the volume accessible to the dye, increased the lobe weight. Despite this increase in weight, histamine infusion resulted in a decrease in the extra-vascular volume accessible to 3HOH. These results indicate that these vasoconstrictor stimuli increased the heterogeneity of transit times through the lung lobe and decreased the flowing blood volume. In addition, histamine decreased the size of the perfused microvascular bed, indicating that pulmonary vasoconstriction can influence the local pattern of microvascular perfusion.

Animals↗
PubMed1983

A three-compartment model of the pulmonary vasculature: effects of vasoconstriction.

The venous occlusion experiments provide sufficient data to permit the vascular bed of a dog lung lobe to be mathematically modeled as three serial compartments, each containing a quantifiable resistance separated by equal parallel compliances. To determine how these compartments are related to the sites of vasomotion in the pulmonary vascular bed we investigated the effects of various pulmonary vasomotor stimuli. We found that serotonin, sympathetic nerve stimulation, hypoxia, and prostaglandin F2 alpha increased the pressure drop upstream (arterial) from the site of major lobar compliance. On the other hand, histamine, norepinephrine, epinephrine, and elevation of the cerebrospinal fluid pressure increased the pressure drop downstream (venous) from the site of major lobar compliance. These stimuli either did not affect the pressure drop across the middle compartment or increased it slightly. Thus we conclude that the middle compartment represents vessels located between the muscular arteries and veins including the capillary bed and possibly other small nonmuscular vessels. Further, the average preocclusion pressure in the middle compartment is a microvascular pressure that can be used to evaluate the impact of vasoconstriction on the lobar microcirculation.

Animals↗
PubMed1983

Chronic pulmonary inflammation modulates the fate of proteins administered by the respiratory tract. Organ distribution of radiolabeled proteins.

In a previous report we found that, following intrapulmonary administration of radiolabeled albumin, blood concentrations were higher in rabbits with BCG-induced chronic pulmonary inflammation (CPI) than in normal rabbits. The present study demonstrates that this increased blood concentration was not the result of decreased blood clearance by other organs, indicating that increased absorption through the respiratory tract occurred in the inflamed lungs. In addition, rabbits with BCG-induced CPI had larger hilar lymph nodes and larger concentrations of radioactivity in the hilar lymph nodes, suggesting that the pulmonary lymphatics are a route of increased absorption through inflamed lungs.

Animals↗