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Biomedical subjects

T R Harris

Publications and source records attributed to T R Harris.

At least 19 recordsLinked to original sources
PubMed1992

A fast track to IAIMS: the Vanderbilt University strategy.

In July 1991, Vanderbilt University Medical Center (VUMC) initiated a fast track approach to the implementation of an Integrated Academic Information Management System (IAIMS). The fast track approach has four elements: 1) an integrated organizational structure combining various operational information management units and the academic informatics program into a single entity to enhance efficiency; 2) technology transfer and network access to remote resources in preference to de novo development; 3) parallel IAIMS planning and infrastructure construction; 4) restriction of the scope of the initial IAIMS to permit a manageable implementation project. The fast track approach is intended to provide a truly functional IAIMS within a time period (7 years) associated with other major construction projects such as the building of a replacement hospital.

Integrated Advanced Information Management Systems↗
PubMed1991

Surface area-independent assessment of lung microvascular permeability with an amphipathic tracer.

A combination of an amphipathic-indicator-dilution (ID) diffusing tracer 1,4[14C]butanediol (B) and a hydrophilic tracer ([14C]urea) (U) was hypothesized to provide a capillary surface area- (S) independent assessment of lung microvascular permeability (P). We performed ID studies on isolated perfused dog lungs and administered randomly two interventions, increasing P by alloxan infusion and reduction in S by lobar ligation. The ratio of PS product of U (PSU) to that for butanediol (PSB) was sensitive to changes in P yet insensitive to changes in S. We performed ID studies in which the dependence of PSU and PSB on flow, hematocrit, and plasma protein binding were examined. Measurements of PSU and PSB after flow and hematocrit were changed suggested that these factors have no significant independent effects. From ID and in vitro studies we also found that no significant binding of B to plasma proteins (albumin) occurred. We concluded that ID techniques using B and U provide a consistent measure of P, despite changes in S, hematocrit, plasma protein concentration, and recruitment.

Animals↗
PubMed1990

Effects of ligation and embolization on Kf and multiple tracer measurements in dog lungs.

In isolated blood-perfused dog lungs, the capillary filtration coefficient (Kf) and the permeability-surface area product of urea (PS) were measured to determine their responses to two different methods of altering filtration area: lobe ligation (LL, n = 5) and glass bead embolization (GBE, n = 4) during constant perfusion rates (700 +/- 45 ml/min). When two of three lobes were ligated, Kf decreased (1.36 +/- 0.13 to 0.58 +/- 0.23 g.min-1.cmH2O-1; P less than 0.05), but PS did not change (2.02 +/- 0.4 to 1.71 +/- 0.3 ml/s). Kf per gram of perfused blood-free dry lung weight was unchanged by LL (0.051 +/- 0.17 to 0.052 +/- 0.18 g.min-1.cmH2O-1), indicating that surface area per gram measured by Kf remained the same. However, PS per gram dry lung doubled (0.07 +/- 0.016 to 0.146 +/- 0.06 ml/s; P less than 0.05) after LL, suggesting that recruitment occurred in the remaining lobe. When three lobes were embolized with 200-microns glass beads (0.48 +/- 0.01 g beads/kg body wt), PS decreased (2.1 +/- 0.22 to 0.94 +/- 0.09 ml/s; P less than 0.05), but Kf was not altered (1.01 +/- 0.17 to 1.04 +/- 0.18 g.min-1.cmH2O-1). The constancy of Kf after GBE implies that the vascular pressure increase during the Kf measurement was transmitted to both blocked and flowing vessels and thereby measured the same filtration area before and after GBE. PS decreased significantly after GBE because of a loss of perfused surface area by the beads blocking flow in small arterial vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Lung microvascular transport properties measured by multiple indicator dilution methods in patients with adult respiratory distress syndrome. A comparison between patients reversing respiratory failure and those failing to reverse.

We conducted indicator dilution studies on the lungs of patients in the early phases of adult respiratory distress syndrome (ARDS) to test the hypothesis that capillary permeability was increased in patients with respiratory failure. Indicator dilution studies were performed using 51Cr-erythrocytes, 125I-albumin, 14C-urea, and 3H-water as tracers. The injectate was infused as a bolus into a central venous line. Peripheral arterial blood was collected and counted for radioactivity. Mathematical analysis of the indicator curves yielded cardiac output, measures of the product of capillary permeability and surface area for urea (PS and D1/2S), the intravascular lung volume (Vv), and the extravascular lung water volume (Ve). Permeability was separated from surface area by normalizing PS and D1/2S to Vv. Patients could be divided into 16 in whom blood gas determinations and radiologic criteria for ARDS were reversed and 23 in whom they were not. We examined indicator dilution and other measures of lung function in the two groups to determine whether significant differences in microvascular function existed. PS and PS/Vv were significantly higher in the nonreversal patients. Ve was above normal, but not different between groups. Linear regression analysis showed significant correlations for all of the following in the nonreversal group: Ve and all measures of permeability, pulmonary vascular resistance (PVR), and the inverse of permeability-surface area measures and AaDO2 and PVR. Only measures of Ve and PS correlated in the reversal group. These results support the hypothesis that capillary permeability is increased in patients with early ARDS and continuing respiratory failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗
PubMed1989

The optical measurement of 1,2-propanediol for the determination of lung capillary permeability surface area.

A technique has been developed which allows for the optical measurement of the concentration-time relationship for a diffusion-limited material in indicator dilution studies. The material, 1-2 propanediol, is used as a probe of the permeability of capillaries in the lung. Comparisons between standard radioisotope measurements and the optical measurements are provided and show excellent agreement. The optical method represents an improvement over the standard radioisotope method in that it provides the same data at lower cost, lower risk, and without the delay required by the radiographic methods.

Animals↗
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↗
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

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

Lung water and vascular permeability-surface area in premature newborn lambs with hyaline membrane disease.

Extravascular lung water and vascular permeability-surface area products were measured with a multiple indicator dilution method in 6 premature lambs with hyaline membrane disease 1-5 hours following delivery by cesarean section. The indicators used were 51Cr-labelled erythrocytes, 125I-albumin, 3H-water, and 14C-urea. Results were compared with previously obtained data in newborn lambs without hyaline membrane disease also delivered by cesarean section. Extravascular lung water was significantly higher in lambs with hyaline membrane disease [23.2 +/- 1.0 (SEM) vs. 10.7 +/- 1.4 ml/kg body wt]. Vascular permeability-surface area products for 14C-urea were significantly lower in lambs with hyaline membrane disease (0.30 +/- 0.10 vs 0.78 +/- 0.11 ml/s per kg). It is concluded that extravascular lung water is high in lambs with hyaline membrane disease. Permeability-surface area products for 14C-urea is low in lambs with hyaline membrane disease, which probably indicates a decrease in detectable surface area for exchange due to derecruitment or hypoperfusion of pulmonary exchange vessels in edematous and hypoxic areas of the lungs.

Animals↗
PubMed1987

Correlation of permeability with the structure of the endothelial layer of pulmonary artery intimal explants.

Changes in vascular permeability are associated with structural damage to endothelial cells. These functional and structural changes can be produced experimentally and examined by using intimal explants from bovine pulmonary artery. Correlation of functional with structural changes allows us to dissect the mechanisms responsible for endothelial damage. We have shown that incubation of intimal explants with histamine causes transient formation of interendothelial dilatations and an increased rate of equilibration of tritiated water and [14C]sucrose across the intimal explant. Exposure to endotoxin also causes interendothelial dilatations but the endothelial damage is more severe than that with histamine, and in vivo experiments show a more prolonged increase in pulmonary vascular permeability. Leukocyte migration has also been suggested to result in a decreased barrier function of the endothelial layer. Experiments with the endothelial layer of intimal explants and separated bovine leukocytes suggest that transendothelial migration may depend on the chemotactic stimulus. Neither granulocyte migration toward zymosan-activated plasma nor lymphocyte migration toward lymphocyte-conditioned medium (RPMI in which lymphocytes were incubated with concanavalin A) leads to detectable increases in explant permeability, but granulocyte migration toward lymphocyte-conditioned medium does result in increased equilibration of [14C]sucrose. Finally, a theoretical model has been used to examine the permeability changes seen for the intimal explants exposed to histamine. The model consists of two compartments with radioactive tracers diffusing across a filter of known permeability. Such a model gives good agreement with data obtained in intact sheep, indicating that mathematical models allow quantitative estimates of barrier function in intimal explants that compare favorably with in vivo data.

Animals↗
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↗
PubMed1986

Effect of sodium bicarbonate and sodium bentonite on digestion, solid and liquid flow, and ruminal fermentation characteristics of forage sorghum silage-based diets fed to steers.

Six ruminally cannulated steers, five Holsteins and one Hereford (250 to 295 kg), were fed 84% forage sorghum silage plus 16% supplement or 50% forage sorghum silage plus concentrate and supplement diets containing either no addition (controls), 1% sodium bicarbonate (NaHCO3) or 2% sodium bentonite in a 2 X 3 factorial arrangement of treatments in a 6 X 6 Latin-square experiment with 3-wk periods. Sodium bicarbonate increased dry matter (DM) intake when concentrate was included, but neither compound affected intake of the 84% silage diet. Bentonite lowered DM, neutral detergent fiber (NDF), and acid detergent fiber (ADF) digestibilities, but NDF disappearance from nylon bags was unchanged. Ruminal pH, osmolality and L(+) and D(-) lactate were not affected by treatment. Both NaHCO3 and bentonite tended to lower ruminal NH3-N concentrations. Bentonite lowered the molar proportion of isobutyrate in ruminal fluid relative to controls, but proportions of other volatile fatty acids (VFA) and total VFA concentrations were unchanged. Neither NaHCO3 nor bentonite affected ruminal liquid or solid volumes, dilution rate constants or ruminal outflow rates. Markers overestimated volumes, but correction with measured volumes did not change interpretation of treatment effects. It was concluded that control diets had sufficiently high baseline values of pH, dilution rate and acetate proportion to preclude changes induced by either compound, especially at 1 or 2% of DM intake. An effect on palatibility through neutralization of silage acids may have been responsible for the intake response to NaHCO3.

Animal Feed↗
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

Lung vascular transport at controlled pressures with reduced coronary flow in sheep.

This study was performed to measure the effects of sustained coronary flow reduction on lung lymph flow and protein clearance at normal and elevated lung microvascular pressures. Eleven halothane-anesthetized sheep were provided with lung lymph and carotid-to-left-anterior-descending coronary artery cannulas. Six sheep (ischemic group) were observed in a protocol of five periods, each of 2 hr duration: baseline, left atrial pressure (PLA) increased by mitral valve obstruction, return to baseline, reduced coronary flow, and reduced coronary flow plus increased PLA. Five sheep (control group) were studied in an identical protocol except that coronary flow was not reduced. PLAS were equal in the second and fifth periods. Lung lymph flow QL and protein clearance (QL times the lymph-to-plasma protein concentration ratio) normalized to second baseline were greater during ischemia than in the comparable control period, and clearance was also greater during the second increased-pressure period. We conclude that reduced coronary flow is related to sustained, significant increases in lung vascular transport at elevated as well as at normal vascular pressures.

Animals↗
PubMed1985

Relation of blood-free to blood-inclusive postmortem lung water measurements in sheep.

Our purpose was to see if the postmortem weight ratio of extravascular lung water to blood-free dry lung (blood-free ratio) was related to similar ratios in blood-inclusive lung and in blood. We developed linear regressions of blood-free ratio on ratios for blood-inclusive lung and blood together and for blood-inclusive lung alone for 73 sheep studied under 11 different protocols and for two subgroups of sheep, one with plasma space expansion and the other without expansion. The relation of ratios of blood-free to blood-inclusive lungs was different between the two subgroups. Although all regressions were highly correlated, the fits of the blood-free ratio on ratios for blood-inclusive lung and blood together were better than for blood-inclusive lung alone. The mean error of prediction of extravascular lung water for all sheep was significantly less for the regression of blood-free ratio on ratios for blood and blood-inclusive lung together (11 g) than for blood-inclusive lung alone (18 g). This study shows that weights of lung homogenate and blood samples before and after simple oven drying can be used to provide accurate inexpensive estimates of postmortem extravascular lung water.

Animals↗