Biomedical subjects

T A Bronikowski

Publications and source records attributed to T A Bronikowski.

At least 19 recordsLinked to original sources

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↗

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↗

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

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↗

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

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

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↗

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

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↗

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

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↗

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↗