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T R Harris

Publications and source records attributed to T R Harris.

At least 73 records · Page 4Linked to original sources
PubMed1982

The exchange of small molecules as a measure of normal and abnormal lung microvascular function.

Evidence exists for the utility of measures of small-molecule exchange in assessing the normal and abnormal transport status of the lung vasculature. The evidence for the usefulness of PS for 14C-urea is: 1. PSu compares to other small molecules as would be expected from free-diffusion coefficients. 2. The extraction of 14C-urea decreases with increase flow as would be expected of a diffusion-limited indicator. 3. PSu is unaffected by moderate pressure increase, it increases when lymph protein flow indicated permeability increase, and it decreases when surface area is reduced. 4. Lung injuries such as E. coli endotoxemia in sheep and ARDS in patients can both reduce PSu, presumably through surface area reduction, and increase PSu, through increased permeability. Two events that accompany clinically important vascular injury complicate the interpretation of lung MT curves. These events are surface area loss and heterogeneity of flow and transport properties in the lung. Additional work is needed to precisely measure these variables and assess their importance.

Animals↗
PubMed1982

Effect of changing lung mass on lung water and permeability-surface area in sheep.

The effects of changing cardiac output and lung mass on pulmonary capillary surface area, lung water, and hemodynamics were studied in eight sheep. 51Cr-erythrocytes, 125I-albumin, 3H2O, and [14C]urea were injected into the right atrium, and timed samples were collected from the aorta for the calculation of cardiac output (CO), extravascular lung water (EVLW), and permeability-surface area product (PS) for [14C]urea. CO was varied by opening and closing arteriovenous shunts, and lung mass was decreased by first tying off the left lung followed by tying off the right lower lobe. Pulmonary arterial pressure (r = -0.741) and pulmonary vascular resistance (r = -0.700) increased as lung mass was decreased. CO decreased slightly (r = -0.470 while left atrial pressure was not changed (r = -0.144) by decreasing lung mass. There was a close correlation between EVLW and lung mass (r = 0.944) and between [14C]urea PS and lung mass (r = 0.672). We were able to demonstrate that [14C]urea behaves as a diffusion-limited tracer in a single pass through the lungs, since [14C]urea extraction decreased as flow per unit mass increased. These results support the clinical use of multiple-tracer studies to measure EVLW and [14C]urea PS.

Animals↗
PubMed1981

Concurrent increases in resistance and transport after coronary obstruction in dogs.

We have extended earlier studies on coronary vascular permeability-surface area (PS) for [14C]sucrose to include observations of the transcoronary flow resistance before and after partial occlusion of the left anterior descending coronary artery. Multiple-tracer (MT) studies were conducted on 13 anesthetized dogs by inserting an isotope mixture (125I-albumin, 51Cr-red blood cells, [14C]sucrose, 3HOH) into a cannula connecting the carotid and the left anterior descending coronary artery. Analysis of blood sampled from the coronary sinus allowed calculation of PS, extravascular 3HOH volume (VT), and extravascular [14C]sucrose volume (VS). Flow reduction significantly reduced VT and VS and increased PS/VT relative to base line. Coronary resistance distal to the obstruction (R) decreased significantly immediately after flow reduction but then, over the low-flow period, increased significantly above this initial low-flow value. The mean R during reduced flow normalized to R immediately after flow reduction (Ri) correlated significantly with PS/VT during ischemia. Because R/Ri is not correlated with VT alone, we speculate that capillary permeability alterations may play a role in the deterioration of myocardial perfusion during ischemia.

Animals↗
PubMed1981

A theoretical model of protein, fluid, and small molecule transport in the lung.

The purposes of this research were to derive a mathematical model of blood-intestinal transport for the lung and to study the ability of this model to describe the results of previous lymph-collection and multiple-indicator experiments on the lungs of unanesthetized sheep. We used a three-pore model of the microvascular barrier to describe lymph flow, lymph-to-plasma ratios (L/P) of eight endogenous proteins, and the microvascular permeability-surface area (PST) of the lungs to [14C]urea in sheep experiments under base-line conditions and after acute elevation of the left atrial pressure. The results indicate that endothelial pathways consisting of a small pore (28 A), intermediate pore (180 A), and a large pore (1,000 A) can describe experimental L/P values and PST. The description of lymph flow required either than interstitial fluid pressure increase with left atrial pressure or that postcapillary venous resistance decrease relative to precapillary values. We concluded that multiple-pore theory is a useful approach to the description of lung blood-interstitial transport.

Animals↗
PubMed1981

Effects of graded increases in pulmonary vascular pressures on lung fluid balance in unanesthetized sheep.

Fourteen experiments were conducted on 12 chronically instrumented unanesthetized sheep in which we monitored pulmonary arterial, left atrial, and aortic pressures, lung lymph flow, and lymph-to-plasma ratios (L/P) of total proteins and four endogenous protein fractions during baseline and progressive elevations of left atrial pressure. We found that L/P for total proteins decreased as lung lymph flow increased until lymph flow exceeded four to five times baseline and thereafter remained nearly constant (filtration independent) at 0.26. The four protein fractions exhibited a filtration independent L/P that was related to the effective molecular radius of the protein fraction. The minimal L/P were 0.36, 0.28, 0.18, and 0.09 for the protein fractions that had effective molecular radii of 36, 38.5, 59, and 101 A, respectively. In addition, we found no evidence supporting a stretched pore phenomenon over the pressure range utilized in this investigation.

Anesthesia↗
PubMed1981

Effects of hyaluronidase and protamine on resistance and transport after coronary flow reduction in heparinized dogs.

We have measured the effects of hyaluronidase, protamine and a mixture of the two drugs on coronary flow resistance and transcapillary exchange in 20 heparinized, anesthetized dogs in which flow to the left anterior descending coronary artery was supplied through an extracorporeal shunt from the carotid artery. Multiple-tracer measurements were made by injecting a mixture of isotopes into the shunt and sampling from the coronary sinus. These were carried out under base-line conditions, after 1 hr of reduced flow to the left anterior descending coronary artery and after a 2nd hr during which the drug under study was infused into the ischemic zone. The results of multiple-tracer measurements were expressed as extravascular water volume (VT), extravascular sucrose volume (VS) and microvascular permeability surface area for sucrose. It was found that flow reduction significantly reduced VT, VS and permeability surface area. Resistance increased during the period of reduced flow after an initial decrease immediately upon flow reduction. In five dogs, a mixture of hyaluronidase and protamine significantly lowered coronary flow resistance and increased permeability surface are, VT, VS and VS/VT compared to preinfusion, reduced flow values. Infusion of hyaluronidase alone had significantly less effect in five other dogs, whereas infusion of protamine alone (N = 5) and saline (N = 5) did not affect resistance or transport. It is concluded that protamine enhances the effects of hyaluronidase when heparin is present, probably by preventing its blockade of hyaluronidase action.

Animals↗
PubMed1980

Lung water and vascular permeability-surface area in newborn lambs delivered by Caesarean section compared with the 3-5 days-old lamb and adult sheep.

Extravascular lung water and vascular permeability-surface area products were measured with a multiple indicator dilution method in five unanaesthetized newborn lambs 2 to 7 h following delivery by Caesarean section at a gestational age of 135-142 days. The indicators used were 51Cr-labelled erythrocytes, [125I] albumin, [3H] water and [14C] urea. Post-mortem determination of extravascular lung water and dry bloodless lung weight were also performed. The results were compared with previously obtained data in unanaesthetized 3-5 days-old lambs and adult sheep. Normalized to dry lung weight, extravascular lung water by both techniques was significantly higher in lambs after Caesarean section than in either the 3-5 days-old lambs or the adult sheep (P less than 0.05). (Indicator values = 3.9 +/- 0.2 (SEM) ml/g for Caesarean section lambs, 3.1 +/- 0.3 for 3-5 days-old lambs and 3.3 +/- 0.5 for adult sheep; post-mortem values were 6.12 +/- 0.28 g/g for after Caesarean section lambs, 4.07 +/- 0.26 for 3-5 days old lambs and 4.03 +/- 0.17 for sheep). Vascular permeability-surface area product for [14C] urea, computed by a mathematical model, was significantly higher (P less than 0.05) in lambs after Caesarean section than in adult sheep (0.18 +/- 0.02 compared with 0.10 +/- 0.03). In 3-5 days-old lambs the value was 0.16 +/- 0.04. It is concluded that, when normalized to dry lung weight, lung following Caesarean section delivery near the end of gestation. Adult values for lung water have been reached by the age of 3-5 days.

Adaptation, Physiological↗
PubMed1979

Isoproterenol and aminophylline reduce lung capillary filtration during high permeability.

Pseudomonas bacteremia in sheep causes a prolonged increase in lung vascular permeability to protein. Isoproterenol and aminophylline could effect lung fluid balance after Pseudomonas by reducing vascular pressures or by blocking release of permeability mediators. We measured vascular pressures, lung lymph flow, and lymph and plasma protein concentrations in unanesthetized sheep under baseline conditions and during steady-state increased permeability after Pseudomonas. Pseudomonas caused pulmonary vascular pressures to rise and lung lymph flow to increase fivefold, but lymph/plasma protein concentration did not change. Pulmonary vascular pressures and lung lymph flow decreased during intravenous infusion of isoproterenol and aminophylline. The decrease in lymph flow after isoproterenol and isoproterenol plus aminophylline was linearly related to the decrease in microvascular pressure (r = 0.71). Lymph/plasma total protein concentration ratios and lymph clearance of proteins with molecular radii 36--96 A remained high during isoproterenol and aminophylline. These drugs can substantially reduce transvascular filtration primarily because they reduce lung vascular pressures.

Aminophylline↗
PubMed1979

Increased lung lymph transport without heart failure after coronary ligation in sheep.

Pulmonary edema frequently accompanies acute myocardial infarction (MI). We measured pulmonary arterial (PAP), left atrial (LAP), and aortic pressures (AP),lung lymph flow (QL), and clearance of total serum protein and each of eight protein fractions in five anesthetized sheep before and after coronary artery ligation. After a stable base line of 1 h, ligation produced significant increases in LAP, QL, and clearance of total protein and four protein fractions, but no significant changes in PAP, AP, or lymph-to-plasma total protein concentration ratio (CSL/CSP). Variables returned to pre-MI levels within 2 h after occlusion. The ratio of wet to dry lung weight measured 2 h after ligation was within normal limits. Two sheep in which the time course of postligation LAP was duplicated by left atrial balloon inflation showed no change in QL. The QL changes seen cannot be caused by LAP increase alone without substantial decrease in CSL/CSP. Increased QL with high CSL/CSP is typical of increased lung vascular permeability, which is a plausible explanation of our results.

Animals↗