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Biomedical subjects

C A Dawson

Publications and source records attributed to C A Dawson.

At least 91 records · Page 5Linked to original sources
PubMed1992

Distensibility of small veins of the dog lung.

To determine the distensibility of the intrapulmonary veins (250-2,900 microns diam) of the dog lung, we obtained X-ray angiograms from isolated lung lobes over a vascular pressure range of approximately 0-30 Torr. Over this pressure range the diameter vs. pressure curves tended to flatten out at the high pressures. In the pressure range of 0-19 Torr, we characterized the vessel distensibility by alpha (the ratio of the slope, beta, of the graph of diameter vs. intravascular pressure to the intercept, Do). The average value of alpha was approximately 1.2%/Torr. There was a weak negative correlation (r = -0.32) between alpha and Do. Infusion of enough norepinephrine to produce approximately 50% increase in total lobar vascular resistance produced a decrease in Do and alpha of approximately 33 and 32%, respectively.

Angiography↗
PubMed1991

A hemodynamic model representation of the dog lung.

The published morphometric data from human, cat, and dog lungs suggest that the power-law relationships between the numbers (Na and Nv) and diameters (Da and Dv) of arteries and veins and between the lengths (La and Lv) and diameters of the arteries and veins could be used as scaling rules for assigning dimensions and numbers to the intrapulmonary vessels of the arterial and venous trees of the dog lung. These rules, along with the dimensions of the extrapulmonary arteries and capillary sheet and the distensibility coefficients of the vessels obtained from the literature, were used to construct a steady-state hemodynamic model of the dog lung vascular bed. The model can be characterized approximately by 15 orders of arteries with Na approximately 2.07 Da-2.58 and 13 orders of veins with Nv approximately 2.53 Dv-2.61. For the intrapulmonary vessels (orders 1-12), La approximately 4.85 Da1.01, and Lv approximately 6.02 Da1.07. The average ratio of the numbers of vessels in consecutive orders is approximately 3.2 for the arteries and veins. These arterial and venous trees are connected by the capillary sheet with an undistended thickness of approximately 3.5 microns and an area of 33 m2. The average distensibility (% increase in diameter over the undistended diameter/Torr increase in transmural pressure) for the model arteries and veins is approximately 2.4%/Torr, and the distensibility of the capillary sheet (% increase in thickness over the undistended thickness/Torr increase in transmural pressure) is approximately 3.6%/Torr. The calculated arterial-capillary-venous volumes and compliances of the model agree well with experimental estimates of these variables in dogs. In addition, the model appears consistent with certain aspects of the pressure-flow relationships measured in dog lungs. The model appears to be a useful summary of some of the available data on pulmonary morphometry and vessel properties. It is anticipated that the model will provide the basis for dynamic modeling of the dog lung in the future.

Animals↗
PubMed1991

Effect of vasoconstriction on longitudinal distribution of pulmonary vascular pressure and volume.

We used an improved version of the low-viscosity bolus method to evaluate longitudinal (arterial-to-venous) differences in the sensitivity of the dog lung lobe vasculature to selected vasoconstrictor stimuli, including hypoxia, and serotonin, histamine, and norepinephrine infusions. This method revealed a bimodal distribution of local vascular resistance vs. cumulative vascular volume under the zone 3 conditions studied. Our interpretation of the two modes of relatively high resistance is that they correspond to high resistance per unit volume segments of the arteries and veins upstream and downstream from the relatively low resistance per unit volume capillary bed. Thus an increase in the height of the upstream and downstream modes of the resistance distribution suggests constriction in small arteries and veins, respectively. Horizontal displacement of the modes along the cumulative volume axis suggests changes in the distribution of volume among the arteries, veins, and capillary bed. By use of these criteria, the results are consistent with the concept that each of the vasoconstrictor stimuli studied had a different longitudinal response pattern. Hypoxia constricted mainly small arteries, whereas serotonin constricted small and large arteries. Histamine constricted large and small veins, and norepinephrine constricted large and small veins and arteries.

Animals↗
PubMed1991

Localization of the sites of pulmonary vasomotion by use of arterial and venous occlusion.

In this study, we present a new approach for using the pressure vs. time data obtained after various vascular occlusion maneuvers in pump-perfused lungs to gain insight into the longitudinal distribution of vascular resistance with respect to vascular compliance. Occlusion data were obtained from isolated dog lung lobes under normal control conditions, during hypoxia, and during histamine or serotonin infusion. The data used in the analysis include the slope of the arterial pressure curve and the zero time intercept of the extrapolated venous pressure curve after venous occlusion, the equilibrium pressure after simultaneous occlusion of both the arterial inflow and venous outflow, and the area bounded by equilibrium pressure and the arterial pressure curve after arterial occlusion. We analyzed these data by use of a compartmental model in which the vascular bed is represented by three parallel compliances separated by two series resistances, and each of the three compliances and the two resistances can be identified. To interpret the model parameters, we view the large arteries and veins as mainly compliance vessels and the small arteries and veins as mainly resistance vessels. The capillary bed is viewed as having a high compliance, and any capillary resistance is included in the two series resistances. With this view in mind, the results are consistent with the major response to serotonin infusion being constriction of large and small arteries (a decrease in arterial compliance and an increase in arterial resistance), the major response to histamine infusion being constriction of small and large veins (an increase in venous resistance and a decrease in venous compliance), and the major response to hypoxia being constriction of the small arteries (an increase in arterial resistance). The results suggest that this approach may have utility for evaluation of the sites of action of pulmonary vasomotor stimuli.

Animals↗
PubMed1991

Effect of atelectasis and surface tension on pulmonary vascular compliance.

The effects of atelectasis and surface tension on the vascular volume and compliance in an isolated perfused dog lung lobe were studied using vascular occlusion and indicator-dilution methods. Measurements were made during atelectasis and again after the lobes were inflated with either a gas mixture (air) or 0.9% saline. Inflation with air resulted in a 20% increase in vascular volume (P less than 0.02), whereas saline inflation had no effect on vascular volume. Inflation with either air or saline increased static vascular compliance by approximately 58% (P less than 0.001) and dynamic vascular compliance by approximately 85% (P less than 0.001). The larger dynamic compliance in the inflated lobes appears to have been mainly due to a larger microvascular compliance. The results suggest that atelectasis can result in a stiffer pulmonary capillary bed. This effect appears to be due primarily to the reconfiguration of the lung tissue structure, because replacing the air with an incompressible fluid did not have the same effect.

Animals↗
PubMed1991

Perfusate cytochrome c reduction in isolated rabbit lungs.

The reduction of ferricytochrome c within the perfusate in isolated lung perfusion systems has been demonstrated previously. We carried out the present study 1) to determine what reducing agents might be responsible for this reduction and 2) to determine whether the cytochrome c (cyto c) reduction within the recirculating perfusion system can be accounted for by relatively stable reducing agents released into the perfusate or whether some of the reduction is dependent on short-lived agents and/or proximity to the source of the agents within the lungs. Experiments were carried out with the use of isolated rabbit lungs perfused for 1 h in a recirculating system. In one group of experiments, ferricytochrome c was included in the recirculating perfusion system. In another group, the cyto c was added to produce the same concentration in samples after they were removed from a cyto c-free recirculating system. The recirculating cyto c was reduced at a rate of approximately 1.76 mumol/h, and approximately 22% was inhibitable by superoxide dismutase. Most of the rest could be inhibited by ascorbate oxidase within the recirculating perfusate. When the ferricytochrome c was added to the samples removed from the cyto c-free perfusion system, virtually the entire cyto c reducing capacity was inhibitable by ascorbate oxidase. Although reduced glutathione did accumulate in the recirculating perfusate, the quantity was not sufficient to have an important role in the cyto c reduction. We conclude that most of the cyto c reducing capacity within the lung perfusate could be accounted for by ascorbate released from the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Distensibility of small arteries of the dog lung.

To obtain in situ measurements of the distensibility of small (100- to 1,000-microns-diam) pulmonary arterial vessels of the dog lung, X-ray angiograms were obtained from isolated lung lobes with the vascular pressure adjusted to various levels. The in situ diameter-pressure relationships were compared with the diameter-pressure relationships for small arteries that were dissected free from the lungs and cannulated with small glass pipettes for the measurement of diameter and transmural pressure. The diameter-vascular or diameter-transmural pressure curves from both in situ and cannulated vessels were sufficiently linear in the pressure range studied (0-30 Torr) that they could be characterized by linear regression to obtain estimates of D0, the diameter at zero vascular pressure, and beta, the change in diameter (micron) per Torr change in pressure. The vessel distensibility coefficient (alpha) was defined as alpha = beta/D0. The mean values of alpha were approximately 2.0 +/- 0.8%/Torr (SD) for the in situ vessels and 1.7 +/- 0.6%/Torr for the cannulated vessels, with no statistically significant difference between the two methods. The influence of vasoconstriction elicited by serotonin was evaluated in the in situ vessels. Serotonin-induced vasoconstriction caused a decrease in D0 and little change in alpha.

Animals↗
PubMed1991

An algorithm for angiographic estimation of blood vessel diameter.

This study was carried out in an attempt to develop an objective and robust method for measuring changes in the diameters of small blood vessels from X-ray angiographic images. Recognizing potential problems with edge detection methods applied to cylindrical vessels in which the contrast diminishes as the boundary is approached, we have attempted to utilize the X-ray absorbance data across the entire cross section of the vessel. Then, assuming a cylindrical geometry, the absorbance data are fit to the cylindrical absorbance function by use of nonlinear regression analysis. The method was tested and calibrated using glass tubes filled with various concentrations of contrast medium. The diameters of small pulmonary arteries were estimated by applying the method of angiograms obtained from an isolated dog lung lobe. The structure of the residuals obtained after the fitting procedure was analyzed to test the appropriateness of the model for use with images of vessels. The results suggest that this approach will have utility for systematically quantifying vessel dimensions.

Algorithms↗
PubMed1991

Tolerance of the isolated perfused lung to hyperthermia.

With the use of in vivo isolated lung perfusion for targeting antitumor therapy in the treatment of lung cancer, tolerance of normal lung tissue to the tumoricidal conditions becomes the limiting factor. This study was performed to determine the short-term tolerance of the lung to hyperthermia. Isolated dog lung lobes were perfused with autologous blood or an artificial salt solution at constant flow. Measurements of lung weight, extravascular water, vascular volume, serotonin uptake, urea permeability surface area product, perfusion pressure, and lung compliance were made with the temperature at about 37 degrees C. The temperature was then set at between 37 degrees and 45 degrees C, and at the end of the subsequent 2 hours the measurements were repeated. When the temperature was less than about 44.4 degrees C, hyperthermia had no detectable influence on the measured variables. Thus on the time frame consistent with in vivo perfusion therapy the normal lung appears to tolerate a fairly severe hyperthermia.

Animals↗
PubMed1990

Lung angiotensin-converting enzyme kinetics from indicator-dilution and constant-infusion methods.

We compared the results of three methods used to evaluate the kinetics of benzoyl-phenylalanyl-alanyl-proline (BPAP) hydrolysis by angiotensin-converting enzyme in the isolated rabbit lung. In method A, the arteriovenous concentration differences at each of four rates of BPAP infusion were used to determine the effect of concentration on the rate of BPAP hydrolysis. In methods B1 and B2, trace doses of [3H]BPAP were injected during each constant infusion of unlabeled BPAP so that the venous [3H]BPAP concentration could be used to estimate the venous BPAP concentration and the rate of hydrolysis at each background concentration. In method C, three boluses containing different amounts of unlabeled BPAP as well as tracer [3H]BPAP were injected such that each bolus resulted in a range of concentrations and hydrolysis rates that could be estimated from the venous concentrations of [3H]BPAP. Each method provided the data needed to calculate the maximum uptake rate (Vmax) and Km, the concentration at half Vmax, assuming that the hydrolysis can be represented by the Michaelis-Menten equation. However, the mathematical model underlying each method involved different assumptions about the effects of heterogeneity of capillary transit times and bolus dispersion. The mean values of Vmax were 180, 216, 217, and 200 nmol/s and for Km 7.8, 10.4, 8.6, and 10.0 microM for methods A, B1, B2, and C, respectively. The differences between methods were not statistically significant. These results suggest that theoretical differences between the methods did not have a quantitatively important impact relative to other factors contributing random errors to each of the methods. The choice between methods can therefore be made on practical grounds.

Animals↗
PubMed1990

Distribution of pulmonary capillary transit times in recruited networks.

When pulmonary blood flow is elevated, hypoxemia can occur in the fastest-moving erythrocytes if their transit times through the capillaries fall below the minimum time for complete oxygenation. This desaturation is more likely to occur if the distribution of capillary transit times about the mean is large. Increasing cardiac output is known to decrease mean pulmonary capillary transit time, but the effect on the distribution of transit times has not been reported. We measured the mean and variance of transit times in single pulmonary capillary networks in the dependent lung of anesthetized dogs by in vivo videofluorescence microscopy of a fluorescein dye bolus passing from an arteriole to a venule. When cardiac output increased from 2.9 to 9.9 l/min, mean capillary transit time decreased from 2.0 to 0.8 s. Because transit time variance decreased proportionately (relative dispersion remained constant), increasing cardiac output did not alter the heterogeneity of local capillary transit times in the lower lung where the capillary bed was nearly fully recruited.

Animals↗
PubMed1989

Effect of propranolol on the first pass uptake of fentanyl in the human and rat lung.

The first pass uptake of fentanyl in the human lung was studied in two groups of patients using a double indicator dilution technique. A bolus containing fentanyl and indocyanine green dye (ICG) was rapidly injected into the central venous catheter of patients prior to anesthesia. Sequential arterial blood samples were collected at 1-s intervals for 45 s after injection. The total amount of fentanyl taken up by the lung during the first pass and the instantaneous extraction of fentanyl 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. In patients who had been receiving no other drugs prior to the experiment, the total first pass uptake (mean +/- SE) of fentanyl was 82.6% +/- 1.4% of the injected dose. In patients who had been receiving 30-120 mg/day of propranolol the total first pass uptake (mean +/- SE) of fentanyl decreased to 52.8% +/- 6.3% of the injected dose. In one patient on 120 mg of propranolol per day, first pass uptake of fentanyl was only 20.3% of the injected dose. Additional studies in a rat isolated perfused lung preparation coperfused with fentanyl and propranolol also demonstrated that one basic lipophilic amine (propranolol) could inhibit the pulmonary uptake of a second basic lipophilic amine (fentanyl). The high first pass uptake of fentanyl in the human lung limits the rate of entry of this drug into the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effect of transit time on metabolism of a pulmonary endothelial enzyme substrate.

Fractional hydrolysis (M) of the synthetic angiotensin-converting enzyme (ACE) substrate [3H]benzoyl-Phe-Ala-Pro (BPAP) on passage through the isolated dog lung lobe was found to be relatively independent of flow rate and transit time (t). The most commonly expressed explanation for this kind of observation is that recruitment of ACE-containing surface area occurs when flow is increased. To test this, as well as other hypotheses that might explain the behavior of this substrate, we compared M obtained after the first pass of a BPAP-containing bolus through isolated rabbit lungs with that obtained after two sequential passes through the lungs. In this way, we could double t with no change in flow or vascular pressure. We found that, when the second pass occurred within a few seconds of the first, M after both the first and second pass was only slightly larger than that after the first pass alone. If the time between passes was increased to a few minutes, M after the second pass was substantially increased. These results are contrary to the recruitment hypothesis and suggest that this substrate may exist in alternative forms that are in slow equilibrium relative to the capillary t. When albumin was present in the perfusate, an albumin-bound fraction appeared to be one such alternative form. However, experiments carried out using protein-free perfusate suggest the possibility that conformational variants of the substrate may also exist.

Animals↗
PubMed1989

Hydrolysis of a synthetic angiotensin-converting enzyme substrate in dog lungs.

The present study was carried out to begin to evaluate the saturable kinetics of the hydrolysis of a synthetic substrate, benzoyl-phenylalanyl-alanyl-proline (BPAP), for angiotensin-converting enzyme (ACE), by the pulmonary endothelium of the dog using a multiple indicator dilution method. In the experiments, isolated dog lung lobes were perfused with a salt solution containing 5% bovine serum albumin. Boluses containing [3H]BPAP, and various amounts of unlabeled BPAP were injected into the lobar artery, and timed samples of venous effluent were collected. The samples were analyzed to determine the fractional hydrolysis of the injected BPAP. The BPAP hydrolysis on passage through the lungs exhibited the saturable behavior and the relative insensitivity to changing flow rate previously described. Since we have described previously that BPAP behaves as if it exists in two forms, one of which is virtually unhydrolyzable on a single pass through the lungs, a model was formulated to include the influence of the unhydrolyzable form, as well as the saturable hydrolysis of the hydrolyzable form, on the fractional hydrolysis of the injected BPAP. This model provides a new method for estimating the kinetic parameters of BPAP hydrolysis by pulmonary endothelial ACE, and it explains the observation that the fractional BPAP hydrolysis does not vary with flow rate and transit time to the extent predicted by previous models.

Animals↗
PubMed1989

Kinetics of serotonin uptake in isolated rabbit lungs.

The single-pass, bolus-injection method was used to study the effect of serotonin (5-HT) concentration on the extraction of 5-HT by isolated perfused rabbit lungs. The extraction pattern suggested that an uptake model, which includes multiple parallel uptake processes, provided a better representation of the data than the simple Michaelis-Menten equation, which has commonly been used to fit the saturable uptake data in previous studies. In particular, the rabbit lung data could be fit with two such parallel pathways. Since the 5-HT uptake could virtually be completely blocked by imipramine, both pathways can be considered to be carrier-mediated processes. The high-affinity pathway was saturable within the range of concentrations studied, with a Km and Vmax of approximately 0.84 microM and 0.21 nmol.s-1.g wet lung wt-1. The Km for the low-affinity pathway was larger than concentrations for which accurate uptake measurements are practical in the perfused organ. Thus, for the low-affinity pathway, only Vmax/Km was identifiable. Vmax/Km values for the high- and low-affinity pathways were approximately 2.87 and 0.35 ml/s, respectively. The results suggest that it will be worthwhile to investigate the behavior of these uptake parameters in response to changes in lung physiology and endothelial function in future studies.

Animals↗
PubMed1989

Plasma protein binding and endothelial enzyme interactions in the lung.

The influence of plasma albumin binding of the synthetic angiotensin-converting enzyme (ACE) substrate [3H]benzoyl-phenylalanyl-alanyl-proline (BPAP) on BPAP hydrolysis by pulmonary endothelial ACE was studied in isolated rabbit lungs perfused with a salt solution containing either 5% bovine serum albumin (BSA) or 5% dextran. The single-pass indicator-dilution method was used to measure the fraction (M) of [3H]BPAP hydrolyzed. Lung M was greater with albumin-free perfusate than when BSA was present. M decreased as the time (ti) that the BPAP was in contact with the BSA before reaching the lung was increased, suggesting that some BSA binding sites for BPAP were not in equilibrium during bolus transit through the lungs. The M vs. ti data were correlated using a model incorporating both rapid and slow binding kinetics of BPAP and BSA. For the slow BPAP-BSA interaction, the dissociation rate constant was approximately 0.015 s-1, and the fraction of the BPAP bound to these slowly equilibrating sites at equilibrium was approximately 22%. The results indicate that transient plasma protein binding kinetics can affect lung BPAP hydrolysis.

Animals↗
PubMed1989

Influence of size of emboli on extravascular lung water.

We examined the influence of the size of emboli on the vascular volume (QL) and extravascular volume (Qev) accessible to 3HOH during a single pass through an isolated dog lung lobe using the double indicator-dilution method with 125I-human serum albumin as the vascular indicator. As successively more beads of a given diameter (58, 548, or 3,175 microns) were introduced into a lung lobe, a linear relationship between QL and Qev was obtained as they both decreased. The slope of the graph of QL vs. Qev with progressive embolism was directly proportional to the bead diameter. This suggested an approach for estimating the total vascular volume in vessels smaller than the diameter of the beads before embolization, referred to as Qm. If it is assumed that most of the transvascular diffusional exchange of 3HOH occurs in vessels smaller than the smallest beads (mainly capillaries) and that vessel obstruction does not change the ratio of Qev to the perfused capillary volume, the slope of the plot of QL vs. Qev is an estimate of the fraction, Qm/QL, of the total vascular volume in vessels smaller than the bead diameter. In the dog lung lobes studied, Qm/QL was approximately 0.64 for 58-microns vessels, 0.75 for 548-microns vessels, and 0.82 for 3,175-microns vessels. The results suggest that, with occlusion of vessels greater than or equal to 58 microns, 3HOH does not diffuse significantly into unperfused regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗