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Biomedical subjects

T R Harris

Publications and source records attributed to T R Harris.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1984

Effects of blood flow reduction and lymphatic ligation on coronary transport in dogs.

We studied the effects of reduced-flow coronary ischemia and coronary lymphatic ligation on transcapillary movement of albumin. We infused 125I-albumin intravenously into four groups of five anesthetized, open-chest dogs in which external carotid-to-coronary arterial cannulas had been placed. One group was subjected to both lymphatic ligation and ischemia; a second group to lymphatic ligation only; a third group ischemia only; and the fourth was a control group. After 1 hr, 85Sr-microspheres were injected into the cannula. After 2 hr, the animals were sacrificed. Extravascular albumin activities in heart sections that were perfused from the cannula were normalized to extravascular albumin in normal-flow regions. This variable was greater in the lymph-ligated and ischemic groups than in the control, and greater in the combined lymph-ligated and ischemic group than any other group. Relative increase in coronary vascular resistance over the protocol interval correlated significantly with normalized albumin content in the cannulated sections. Although both ischemia and lymph ligation lead to increased extravascular albumin accumulation, their mechanisms are different. Increased extravascular albumin after ischemia may be due to increased capillary permeability.

Albumins↗
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↗
PubMed1984

Influence of endothelial volume on kinetics of reacting indicators in the lung.

The purpose of this work is to show mathematically the relationship between the classical maximum velocity of reaction, Vmax, for enzyme kinetics and an analogous parameter, Vmax, derived by Linehan and Dawson (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47:404-411, 1979) for the analysis of tracers which disappear by saturation kinetics from the lung circulation during the passage of indicators after bolus injection. Rederivation of the original equation for the combination of flow and reaction in a capillary showed that Vmax is equal to the product of enzyme Vmax and the volume of endothelium, Ve, in which the enzyme resides. This implies that Vmax interpreted from multiple-indicator curves in the lung by the Linehan-Dawson method is a combination of an enzyme characteristic Vmax and a measure of functioning capillary surface during passage, Ve. Lung injury could change Vmax, functioning surface (Ve), or both.

Blood Vessels↗
PubMed1984

Reperfusion of the ischemic canine myocardium: effect on vascular exchange and resistance.

In order to see if changes in hemodynamic resistance following reperfusion of ischemic myocardium could be related to alterations in microvascular exchange, we measured resistance (R), permeability surface-area for sucrose (PS), and distribution volumes for tritiated water (V) and for sucrose (VS) in nine anesthetized dogs in which blood to the left anterior descending coronary artery was supplied via a shunt from the carotid artery. Measurements were made during four periods: baseline, reduced coronary artery flow, reperfusion, and a second period of reduced flow. Increase in resistance following reperfusion (R2 = 1.8 +/- 3, R4 = 2.5 +/- .5 mmHg/min/ml, mean +/- s.e.m.) was significantly greater than in nine control dogs in which reperfusion was omitted. Also, the series of interventions including reperfusion lowered PS and V (PS4/PS1 = .54 +/- .07, V4/V1 = .58 +/- .08). Our results suggest that increases in resistance due to reperfusion may be accompanied by a loss in functioning capillary surface area.

Animals↗
PubMed1984

Tracer exchange in the normal and ischemic coronary circulation.

Proper function of the coronary blood-tissue exchange system may be important in the preservation of myocardium threatened by ischemia. We have undertaken studies aimed at elucidating the functions of this system under baseline and ischemic conditions. The exchange of [14C]sucrose between the coronary capillaries and extravascular space has been studied with the multiple-tracer method. Protein transport has been examined by measuring the deposition of labeled albumin and by collecting cardiac lymph. Results indicate that reduced-flow ischemia decreases functioning capillary surface area but increases permeability to small molecules and protein. Hyaluronidase and adenosine can restore flow after partial occlusion of the coronary artery. However, only hyaluronidase restores capillary surface to its baseline value. Thus, ischemic effects on exchange are not controlled merely by hemodynamic factors. Reduced-flow ischemia in the heart can induce a vascular permeability change in the lung circulation. We conclude that capillary and interstitial transport are altered significantly by ischemia. Preservation of the proper function of these processes may be important in protecting the ischemic myocardium.

Animals↗
PubMed1984

Effect of exogenous adenosine on resistance, capillary permeability-surface area and flow in ischemic canine myocardium.

The effects of adenosine on capillary-tissue exchange have not been evaluated. Although adenosine is a known vasodilator, its effects on nutritive flow are unknown. We therefore measured the influence of adenosine on resistance and capillary exchange in normal and mildly ischemic myocardium in 11 anesthetized, heparinized dogs. Flow to the left anterior descending artery was measured and controlled through an extracorporeal shunt from the carotid artery. Capillary permeability-surface area for sucrose (PS) was determined using the multiple-tracer technique in which mixtures of isotopes were injected into the coronary arterial shunt. We found that in the normal myocardium, intracoronary infusion of adenosine at 8 +/- 2 (S.E.M.) micrograms/ml of plasma significantly lowered resistance and increased PS. In the ischemic myocardium, however, large doses of adenosine (200 +/- micrograms/ml of plasma) lowered resistance but failed to increase PS. We interpret these results to mean that in mild, flow-reduction ischemia, adenosine did not lead to a recovery of capillary surface area for exchange, but simply increased flow through capillaries which had already been functioning. Nutritional flow was not enhanced.

Adenosine↗
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↗
PubMed1983

Correlation of oxygenation with vascular permeability-surface area but not with lung water in humans with acute respiratory failure and pulmonary edema.

We used a single-pass multiple tracer technique to measure cardiac output, extravascular lung water (EVLW) and lung vascular [14C]urea permeability-surface area (PSu) in 14 patients with acute respiratory failure and pulmonary edema. All patients had increased EVLW, but EVLW in the 10 surviving patients (0.26 +/- 0.06 SE ml/ml total lung capacity [TLC]) was not significantly different from that in the five patients who died (0.22 +/- 0.05). EVLW did not correlate with intravascular pressures or with alveolar-arterial oxygen pressure difference (A-aDO2). PSu was lower in surviving patients (0.50 +/- 0.16 SE ml/s X liter TLC) than in patients who died (3.44 +/- 0.36; P less than 0.05) and also lower than in previously reported data in patients with normal PSu. PSu correlated significantly with A-aDO2. Serial studies showed that PSu returned from a low value toward normal in a patient who survived but remained high in a patient who died. We conclude that the amount of edema in the lungs measured by indicator methods was not the principal determinant of either the magnitude of oxygenation defect or survival in the patients studied. We interpret the low PSu in surviving patients as decreased surface area and infer that the ability of the lung circulation to reduce perfusion of damaged and edematous areas was important in preserving oxygenation. A high PSu, presumably reflecting perfusion of areas with increased permeability, was a sign of especially poor prognosis. Multiple tracer techniques for measuring lung vascular PSu may help to define the pathogenesis and to evaluate therapies of acute lung injury in humans. Such measurements may be a more useful clinical tool than measurements of lung water in patients with acute respiratory failure and pulmonary edema.

Adult↗
PubMed1983

Comparison of sodium and urea as indicators of pulmonary vascular permeability.

The objective of this work was to compare the blood-tissue transport properties of 14C-urea and 24Na in the lung circulation. The extraction of both substances was measured relative to intravascular reference tracers (125I-albumin for 24Na, 51Cr red cells and 125I-albumin for 14C-urea) in single-pass transpulmonary multiple indicator curves measured in awake sheep. Sheep were studied in baseline condition, after infusion of histamine solution (4 micrograms/kg-min for 4 hr), and after microvascular pressure was elevated. Permeability-surface area was computed for both sodium (PSn) and urea (PSu) by the Crone extraction model and by a mathematical model. In spite of the fact that the free diffusion coefficients of sodium and urea are approximately equal, the mean ratio of Crone PSn/PSu for baseline studies was 0.76. PSu was significantly increased by histamine infusion but PSn was not. The variation in PSn with histamine and increased pressure was marked. Thus, neither manipulation altered the ratio PSn/PSu in a consistent fashion. Correction of PS for extravascular distribution volumes of urea and Na did not change the PS ratio significantly. We concluded that the diffusional resistance to sodium is higher than expected from its diffusivity, possibly because of charge, and that PS for urea is more sensitive to changes in lung vascular permeability.

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↗