PubMed Health⌕ Search

Biomedical subjects

R J Roselli

Publications and source records attributed to R J Roselli.

At least 37 records · Page 2Linked to original sources
PubMed1989

Measurement of lung fluid volumes and albumin exclusion in sheep.

A radioactive tracer technique was used to determine interstitial diethylenetriaminepentaacetic acid (DTPA) and albumin distribution volume in sheep lungs. 125I- and/or 131I-labeled albumin were injected intravenously and allowed to equilibrate for 24 h. 99mTc-labeled DTPA and 51Cr-labeled erythrocytes were injected and allowed to equilibrate (2 h and 15 min, respectively) before a lethal dose of thiamylal sodium. Two biopsies (1-3 g) were taken from each lung and the remaining tissue was homogenized for wet-to-dry lung weight and volume calculations. Estimates of distribution volumes from whole lung homogenized samples were statistically smaller than biopsy samples for extravascular water, interstitial 99mTc-DTPA, and interstitial albumin. The mean fraction of the interstitium (Fe), which excludes albumin, was 0.68 +/- 0.04 for whole lung samples compared with 0.62 +/- 0.03 for biopsy samples. Hematocrit may explain the consistent difference. To make the Fe for biopsy samples match that for homogenized samples, a mean hematocrit, which was 82% of large vessel hematocrit, was required. Excluded volume fraction for exogenous sheep albumin was compared with that of exogenous human albumin in two sheep, and no difference was found at 24 h.

Albumins↗
PubMed1989

Analysis of noninvasive macromolecular transport measurements in the lung.

Several groups of investigators are measuring transcapillary protein flux in the lung using noninvasive methods. Results from these studies are reported using several different protein transport indexes, including pulmonary transvascular transfer coefficient, relative extravascular protein, pulmonary transcapillary escape rate, protein leak index, lung transferrin index, slope index, and lung-to-heart count ratios. The purpose of this study is to discover the relationships between these indexes by employing a two-compartment theory of protein transcapillary transport in the lung. We found that all the above indexes can be related to a single index, which we call the normalized slope index. This index is the time rate of change of radioactivity originating from protein in lung interstitium divided by radioactivity arising from protein in lung plasma, normalized by this ratio at time 0, and corrected for blood volume changes. In particular the normalized slope index is shown to be the same as pulmonary transcapillary escape rate under normal sampling conditions and is relatively unaffected by changes in interstitial volume. The response of the normalized slope index to changes in microvascular pressure and microvascular permeability is explored by applying a two-pore model of the microvascular barrier. Results indicate that the normalized slope index is relatively insensitive to changes in microvascular pressure but is greatly affected by changes in microvascular permeability (i.e., changes in large-pore size or number). Since all published leak indexes are related, we would encourage all investigators in the field to adopt a single leak index. We recommend that when a two-compartment model is applied to external detection data, the results be expressed as pulmonary transcapillary escape rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung↗
PubMed1988

Effect of progressive exercise on lung fluid balance in sheep.

The purpose of this study is to determine the roles of cardiac output and microvascular pressure on changes in lung fluid balance during exercise in awake sheep. We studied seven sheep during progressive treadmill exercise to exhaustion (10% grade), six sheep during prolonged constant-rate exercise for 45-60 min, and five sheep during hypoxia (fraction of inspired O2 = 0.12) and hypoxic exercise. We made continuous measurements of pulmonary arterial, left atrial, and systemic arterial pressures, lung lymph flow, and cardiac output. Exercise more than doubled cardiac output and increased pulmonary arterial pressures from 19.2 +/- 1 to 34.8 +/- 3.5 (SE) cmH2O. Lung lymph flow increased rapidly fivefold during progressive exercise and returned immediately to base-line levels when exercise was stopped. Lymph-to-plasma protein concentration ratios decreased slightly but steadily. Lymph flows correlated closely with changes in cardiac output and with calculated microvascular pressures. The drop in lymph-to-plasma protein ratio during exercise suggests that microvascular pressure rises during exercise, perhaps due to increased pulmonary venous pressure. Lymph flow and protein content were unaffected by hypoxia, and hypoxia did not alter the lymph changes seen during normoxic exercise. Lung lymph flow did not immediately return to base line after prolonged exercise, suggesting hydration of the lung interstitium.

Animals↗
PubMed1988

Effects of endotoxemia on the sheep lung microvascular membrane: a two-pore theory.

We analyzed the effects of Escherichia coli endotoxin infusion on pulmonary microvessels in sheep by using a two-pore mathematical model of the microvascular barrier. Five sheep were prepared with lung lymph fistulas and instrumented to measure pulmonary arterial and left atrial pressures. Multiple indicator-dilution curves (with 125I-labeled albumin, 51Cr-labeled erythrocytes, [14C]urea, and 3H2O) were measured at base line and during phases 1 and 2 of the endotoxin response. Alterations in the membrane integrity in response to endotoxin infusion were quantified by using a two-pore theory of the microvascular barrier that incorporated lymph, protein, pressure, and multiple indicator measurements. The modeling results showed a slight change in the size of the pores during phase 1 but a 56% decrease in the number of small pores and a twofold increase in the number of large pores with respect to base-line values. During phase 2 the large pore size increased by 40%, and the total number of pores returned to base-line values. The analysis showed that endotoxin effects on fluid and protein exchange in the lung cannot be explained by hemodynamic and surface area changes alone. An apparent increase in lung microvascular permeability occurs during phases 1 and 2 of the endotoxin reaction, with a substantial decrease in perfused microvascular surface area during phase 1.

Algorithms↗
PubMed1987

Computer analysis of proteins separated by polyacrylamide gradient pore gel electrophoresis.

A method for measuring lymph-to-plasma (L/P) protein concentration ratios obtained from protein fractions separated by polyacrylamide gradient gel electrophoresis is presented. A curve-fitting technique is used to decompose lymph and plasma electropherograms containing multiple components into individual components, eliminating protein-protein overlap regions. This allows the concentration of each component in the mixture to be measured accurately, yielding more precise estimates of L/P ratios. This technique consists of three phases. Individual electropherograms are constructed for proteins of various sizes by taking a weighted average of measured electropherograms obtained from the two protein standards closest in size to the protein of interest. Using these generated standard curves, the multicomponent lymph and plasma curves are decomposed into the least number of equally spaced components that yield a good fit. A linear least-squares method is used to do this. Each protein fraction is multiplied by the total measured protein concentration to provide a concentration for each component. Finally, L/P concentration ratios of protein fractions with visible peaks were computed by applying an averaging technique to the equally spaced protein fractions. Plots of sheep lung L/P ratio versus protein size obtained in this manner were compared to L/P ratios obtained using a method of analysis which does not correct for protein overlap. The corrected L/P ratios showed less scatter than the uncorrected curves. Lung lymph data analyzed with the correction method indicated an increased lung microvascular permeability for large proteins following endotoxin infusion, whereas the uncorrected curves were too noisy to support this concept.

Animals↗
PubMed1987

Models of lung transvascular fluid and protein transport.

Transport theory has been applied to lymph flow (QL), protein lymph to plasma concentration ratios (L/P), and permeability surface area for urea (PSu) in unanesthetized sheep. Three models of the plasma-interstitial barrier have been used: a single pathway fiber matrix model, a continuous cylindrical-pore model with log normal distribution of filtration coefficients, and a cylindrical two-pore model. The fiber matrix model was unable to match measured PSu, QL, and L/P. The continuous-pore model was capable of describing the data, but the fitted median pore size was inconsistent with a continuum theory. The two-pore model described steady-state data and was used in additional model applications. We explored the 90% confidence limits for the fitted structural parameters of the two-pore theory. We found that many sets of model parameters were capable of fitting the available experimental data. We therefore sought combinations of parameters that might characterize the microvascular barrier under baseline and altered permeability situations. One combination that looks promising is the ratio of large-pore to small-pore radius raised to the sixth power and multiplied by the large-pore frequency. This value remains relatively constant following elevations in microvascular pressure, saline infusions, and plasma infusions but increases dramatically after endotoxin infusion.

Animals↗
PubMed1987

Comparison of labeled propanediol and urea as markers of lung vascular injury.

The purpose of these studies was a comparison of [14C]urea (U) and 1,3-[14C]propanediol (Pr) as measures of lung vascular permeability-surface area (PS) under base-line conditions and after lung injury caused by alloxan infusion in isolated perfused dog lungs. Indicator mixtures of 125I-albumin, 51Cr-red blood cells, 3HOH, and U or Pr were injected under base-line conditions, after 1.2 g of alloxan, and after an additional 0.8 g of alloxan. Indicator-dilution curves were analyzed from sampled outflow blood to provide PS, the square root of effective extravascular diffusivity multiplied by exchange surface area (D1/2S), and extravascular lung water (EVLW) from the tracer mean transit times (VW). Results show that alloxan increases PS and D1/2S for U, D1/2S for Pr, and VW and EVLW by desiccation. All indicator-dilution parameters correlate significantly with alloxan dose. Interpretation of Pr transport suggests that materials with lipid and hydrophilic pathways might be used in conjunction with U to minimize the effects of surface area changes and increase the sensitivity of these tracers to permeability alteration. In addition Pr may be a useful alternative to U as a marker of vascular damage.

Alloxan↗
PubMed1987

Venous occlusion measurement of pulmonary capillary pressure: effects of embolization.

The effects of pulmonary arterial embolization on calculated pulmonary capillary pressure as determined by the venous occlusion technique are examined using a simple pressure-flow model for the lung. It is predicted that pulmonary, arterial embolization can induce significant underestimation of pulmonary capillary pressure in flowing vessels. This underestimation is related to the percent of vessels embolized and the caliber of pulmonary arteries that are embolized (i.e., the size of the emboli). Experimental verification of these theoretical findings is necessary before the conclusions can be extended to the interpretation of venous occlusion experiments in the lung.

Blood Pressure↗
PubMed1986

Effects of inspiratory resistance loading on lung fluid balance in awake sheep.

Because pulmonary edema has been associated clinically with airway obstruction, we sought to determine whether decreased intrathoracic pressure, created by selective inspiratory obstruction, would affect lung fluid balance. We reasoned that if decreased intrathoracic pressure caused an increase in the transvascular hydrostatic pressure gradient, then lung lymph flow would increase and the lymph-to-plasma protein concentration ratio (L/P) would decrease. We performed experiments in six awake sheep with chronic lung lymph cannulas. After a base-line period, we added an inspiratory load (20 cmH2O) and allowed normal expiration at atmospheric pressure. Inspiratory loading was associated with a 12-cmH2O decrease in mean central airway pressure. Mean left atrial pressure fell 11 cmH2O, and mean pulmonary arterial pressure was unchanged; calculated microvascular pressure decreased 8 cmH2O. The changes that occurred in lung lymph were characteristic of those seen after other causes of increased transvascular hydrostatic gradient, such as increased intravascular pressure. Lung lymph flow increased twice base line, and L/P decreased. We conclude that inspiratory loading is associated with an increase in the pulmonary transvascular hydrostatic gradient, possibly by causing a greater fall in interstitial perimicrovascular pressure than in microvascular pressure.

Airway Obstruction↗
PubMed1986

Effects of hypoproteinemia on lung microvascular protein sieving and lung lymph flow.

Experiments were conducted on five chronically instrumented unanesthetized sheep to determine the effects of sustained hypoproteinemia on lung fluid balance. Plasma total protein concentration was decreased from a control value of 6.17 +/- 0.019 to 3.97 +/- 0.17 g/dl (mean +/- SE) by acute plasmapheresis and maintained at this level by chronic thoracic lymph duct drainage. We measured pulmonary arterial pressure, left atrial pressure, aortic pressure, central venous pressure, cardiac output, oncotic pressures of both plasma and lung lymph, lung lymph flow rate, and lung lymph-to-plasma ratio of total proteins and six protein fractions for both control base-line conditions and hypoproteinemia base-line conditions. Moreover, we estimated the average osmotic reflection coefficient for total proteins and the solvent drag reflection coefficients for the six protein fractions during hypoproteinemia. Hypoproteinemia caused significant decreases in lung lymph total protein concentration, lung lymph-to-plasma total protein concentration ratio, and oncotic pressures of plasma and lung lymph. There were no significant alterations in the vascular pressures, lung lymph flow rate, cardiac output, or oncotic pressure gradient. The osmotic reflection coefficient for total proteins was found to be 0.900 +/- 0.004 for hypoproteinemia conditions, which is equal to that found in a previous investigation for sheep with a normal plasma protein concentration. Our results suggest that hypoproteinemia does not alter the lung filtration coefficient nor the reflection coefficients for plasma proteins. Possible explanations for the reported increase in the lung filtration coefficient during hypoproteinemia by other investigators are also made.

Animals↗
PubMed1986

Effect of perfusate hematocrit on urea permeability-surface area in isolated dog lung.

Seven dog lower left lung lobes were statically inflated and perfused at a constant rate for each lobe with a perfusate in which the hematocrit was altered over a wide range. The permeability-surface area of urea was calculated from multiple indicator dilution curves using two separate injectates for each hematocrit level. One injectate contained only 125I-albumin as the vascular reference tracer and the other contained both 51Cr-erythrocytes and 125I-albumin as the vascular reference tracers; both contained [14C]urea as the permeating tracer. The results strongly indicate that the phenomenon of "erythrocyte trapping" of urea does not affect the calculation of urea permeability-surface area product provided the appropriate albumin-erythrocyte composite reference tracer is utilized in its calculation.

Animals↗
PubMed1985

Comparison between pore model predictions and sheep lung fluid and protein transport.

The multiple pore model of T. R. Harris and R. J. Roselli (1981, J. Appl. Physiol: Respir. Environ. Exercise Physiol. 50, 1-14), was used to simulate lung lymph flow and protein transport at various levels of microvascular pressure. Response of the three-pore structure determined in that study was found to be in excellent agreement with the experimental sheep lung lymph measurements of R. E. Parker, R. J. Roselli, T. R. Harris, and K. L. Brigham (1981, Circ. Res. 49, 1164-1172). Optimal one- and two-pore model structures were also determined and their responses compared with the experimental data. The two-pore model behavior was found to be very similar to that of the three-pore model but a homoporous model which reproduced the experimental findings could not be found. All simulations required interstitial fluid pressure to increase as microvascular pressure was elevated. True filtration-independent conditions could only be simulated when lung vascular pressures were raised to physiologically unrealistic values.

Animals↗
PubMed1985

Effects of prolonged elevated microvascular pressure on lung fluid balance in sheep.

Experiments were conducted in seven chronically instrumented unanesthetized sheep to estimate the osmotic reflection coefficient (sigma d) for total proteins and the solvent-drag reflection coefficients (sigma f) for six endogenous protein fractions. We measured the lymph-to-plasma ratio of total proteins (CL/CP) and six protein fractions during base-line conditions and after left atrial pressure elevations of 24-26 h per elevation. We also monitored pulmonary arterial pressure, left atrial pressure, systemic arterial pressure, and lung lymph flow at the various levels of pulmonary microvascular pressure. Our results indicate the CL/CP may require up to 24 h to reach a true steady state. It was found that sigma d is at least 0.89 for total proteins and sigma f is at least 0.84, 0.87, 0.86, 0.92, 0.95, and 0.96 for protein fractions with effective molecular radii of 36, 39.5, 44, 66, 105, and 123 A, respectively. In addition, the sigma f values for various protein fractions obtained from this investigation are compared with the predicted values of various mathematical models of the lung microcirculation.

Animals↗
PubMed1984

A model of unsteady-state transvascular fluid and protein transport in the lung.

Models of steady-state fluid and solute transport in the microcirculation are used primarily to characterize filtration and permeability properties of the transport barrier. Important transient relationships, such as the rate of fluid accumulation in the tissue, cannot be predicted with steady-state models. In this paper we present three simple models of unsteady-state fluid and protein exchange between blood plasma and interstitial fluid. The first treats the interstitium as a homogeneous well-mixed compliant compartment, the second includes an interstitial gel, and the third allows for both gel and free fluid in the interstitium. Because we are primarily interested in lung transvascular exchange we used the multiple-pore model and pore sizes described by Harris and Roselli (J. Appl. Physiol.: Respirat . Environ. Exercise Physiol. 50: 1-14, 1981) to characterize the microvascular barrier. However, the unsteady-state transport theory presented here should apply to other organ systems and can be used with different conceptual models of the blood-lymph barrier. For a step increase in microvascular pressure we found good agreement between theoretical and experimental lymph flow and lymph concentrations in the sheep lung when the following parameter ranges were used: base-line interstitial volume, 150-190 ml; interstitial compliance, 7-10 ml/Torr; initial interstitial fluid pressure, -1 Torr; pressure in initial lymphatics, -5 to -6 Torr; and conductivity of the interstitium and lymphatic barrier, 4.25 X 10(-4) ml X s-1 X Torr-1. Based on these values the model predicts 50% of the total change in interstitial water volume occurs in the first 45 min after a step change in microvascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Analysis of lung multiple indicator data with an effective diffusivity model of capillary exchange.

In this study, we have compared an effective diffusivity model with several models previously used to describe lung microvascular exchange of small molecules (multiple indicator curves): the Crone integral extraction model, the Sangren-Sheppard model, and the Rowlett-Harris model. The parameters of each model were adjusted to achieve a best fit of multiple-tracer data from six isolated dog lung preparations perfused under zone III conditions at three flows and from five awake sheep before and after histamine infusion. The effective diffusivity model was the best at matching the data and the unique falling extraction pattern observed in the lung. When the isolated lung data was analyzed, the permeability-surface area products (PS) of three models were all significantly lower at lower flows. However, the effective diffusivity model parameter (D 1/2 S, an effective diffusivity-surface area product) was not significantly affected by flow reduction. Lung lymph flow and lymph-to-plasma protein ratios from the awake sheep indicated that PS and D 1/2 S should have increased, and except for the Sangren-Sheppard model, all models predicted significantly increased values. By use of sensitivity analysis, the parameters of the effective diffusivity model were found to be more independently determined than those of the Sangren-Sheppard model, but data collected at longer times were necessary to reliably identify the extravascular volume parameter (LS, diffusing distance-surface area product) of the effective diffusivity model. We conclude that the effective diffusivity model is a better descriptor of multiple tracer data from the lung, that its parameters are more reliably and independently determined, and that it more reliably describes the effects of flow and histamine infusion on capillary-tissue exchange.

Albumins↗
PubMed1983

Effects of coronary flow reduction on lung vascular tissue transport in sheep.

This study was performed to measure the effects of a sustained reduction in coronary flow on lung lymph flow and protein content. Ten halothane-anesthetized sheep with cannulated lymphatic vessels were provided with a carotid-to-left anterior descending coronary artery cannula containing an electromagnetic flowmeter. One group of five animals was observed at base line and after coronary flow was reduced to 38% of base line. A second group of five animals acted as controls and was observed at base line, for 111 min of increased left atrial pressure, and a second period of normal pressures. Sustained coronary flow reduction led to significant increases in pulmonary arterial pressure, left atrial pressure, lymph flow, total protein lymph-to-plasma concentration ratio (L/P), and protein lymph clearance (L/P X lymph flow). Analysis of the pressure, lymph, protein, and indicator data with a two-pore model of the microvascular barrier showed that the observations were consistent with the concept that coronary flow reduction decreased functioning lung capillary surface but increased the size of the large pore and the number of small pores relative to the number of larger pores. Control studies showed increases in lymph flow and decreases in L/P with increased pressure but no significant changes in any variable between the first and second period of normal pressures. We conclude that coronary flow reduction increases lung vascular-tissue transport by decreasing the resistance of the microvascular barrier to protein and fluid movement. However, increased pressure secondary to left ventricular dysfunction plays a role in the magnitude of this response.

Animals↗
PubMed1982

Effects of red cell exchange on calculated sheep lung vascular permeability to 14C-urea and 14C-thiourea.

We performed fourteen experiments on sheep to determine whether or not erythrocytes tracer transport alters the calculated value of capillary tracer permeability surface area. In each set of experiments 14C-urea or 14C-thiourea was equilibrated with: (1) a whole blood sample; (2) saline alone, and (3) packed erythrocytes alone. Aliquots of each of these samples were injected separately into the superior vena cava of sheep and multiple indicator data collected from the aorta. Lung urea or thiourea microvascular permeability surface area (PS) was calculated for each set of data using the integral extraction method. These results were compared to the predictions of a detailed theory of microvascular transport which included red cell effects. As predicted by the theory, only small differences were found between urea PS calculations based on pre-equilibrated blood or plasma injectates. When 14C-urea in the injectate was confined to red cells, the average PS calculation was approximately 60% of the average plasma-equilibrated value (also predicted by theory). This ratio was substantially lower (25%) when 14C-thiourea was used as an indicator, suggesting that the red cell membrane, rather than the microvascular barrier, limits thiourea exchange. We conclude that a finite red cel-plasma urea exchange rate does not significantly influence the calculation of lung vascular PS when the injected blood is equilibrated with urea prior to its introduction into the vascular system.

Animals↗