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Biomedical subjects

K L Brigham

Publications and source records attributed to K L Brigham.

At least 163 records · Page 9Linked to original sources
PubMed1980

Arachidonate raises vascular resistance but not permeability in lungs of awake sheep.

Prostaglandins have been implicated as mediators of pulmonary hypertension in a variety of reactions, but the agents responsible for pathological increases in lung vascular permeability have not been determined. To test the hypothesis that products of arachidonic acid metabolism produce pulmonary vasoconstriction and alter lung vascular permeability, we infused purified sodium arachidonate (25-100 micrograms . kg-1 . min-1) into chronically instrumented unanesthetized sheep prepared for collection of lung lymph. Arachidonate produced dose-related increases in pulmonary artery pressure and lung lymph flow with corresponding decreases in the lymph-to-plasma protein concentration ratio. Lung lymph responses were like those caused by mechanically elevating left atrial pressure. Infusion of indomethacin or sodium eicosatetraynoate inhibited hemodynamic and lung lymph responses to arachidonate. We conclude a) that arachidonate must be converted to prostaglandin cyclic endoperoxides to produce pulmonary hypertension and increased flow of protein-poor lung lymph and b) that under normal conditions, no detectable increase in lung vascular permeability results from either arachidonate itself or the combined products of arachidonate metabolism via cyclooxygenase and/or lipoxygenase.

Animals↗
PubMed1980

Diphenhydramine reduces endotoxin effects on lung vascular permeability in sheep.

Because, in sheep, histamine-induced increased lung vascular permeability is prevented by diphenhydramine, we tested the effects of diphenhydramine on the sheep lung vascular response to endotoxin. We infused E. coli endotoxin (0.40-1.00 micrograms/kg) with and without diphenhydramine (3.0 mg/kg bolus + 1.5 mg . kg-1 . h-1) in the same unanesthetized sheep while measuring pulmonary arterial (Ppa) and left atrial (Pla) pressures, lung lymph flow (Qlym) and lymph (L) and plasma (P) protein concentrations. Endotoxin caused pulmonary hypertension soon after infusion (base-line Ppa = 22 +/- 3 (SE) cmH2O; after endotoxin Ppa = 40 +/- 2; P less than 0.05, n = 6) and after several hours an increase in permeability reflected in high flow of protein-rich lymph (base-line; Qlym = 7.5 +/- 1.4 (SE) ml/h, L/P protein concentration = 0.60 +/- 0.02: after endotoxin; Qlym = 21.4 +/- 3.1, P less than 0.05; L/P = 0.66 +/- 0.03, P less than 0.05). In the presence of diphenhydramine, endotoxin caused identical pressure changes but Qlym was lower during the period of increased permeability (16.7 +/- 3.0 (SE) ml/h, P less than 0.05 compared to endotoxin alone) and L/P protein concentration was similar (0.68 +/- 0.04, P = NS). We conclude that endogenous histamine may be partly responsible for the increase in lung vascular permeability after endotoxemia, but that histamine probably is not the sole mediator of the permeability change.

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↗
PubMed1979

Increased sheep lung vascular permeability caused by Escherichia coli endotoxin.

We infused Escherichia coli endotoxin, 0.07-1.33 microgram/kg, intravenously into chronically instrumented unanesthetized sheep and measured pulmonary arterial and left atrial pressures, lung lymph flow, lymph and blood plasma protein concentrations, and arterial blood gases. Endotoxin caused a biphasic reaction: an early phase of pulmonary hypertension and a long late phase of steady state increased pulmonary vascular permeability during which pulmonary arterial and left atrial pressures were not increased significantly and lung lymph flow was 5 times the baseline value. Lymph: plasma total protein concentration ratio during the late phase (0.76 +/- 0.04) was significantly (P less than 0.05) higher than during baseline (0.66 +/- 0.03). The lymph response was reproducible. Lung lymph clearance of endogenous proteins with molecular radii (r) 35.5 to 96 A was increased during the steady state late phase of the reaction, but, as during baseline, clearance decreased as r increased. The endotoxin reaction was similar to the reaction to infusing whole Pseudomonas bacteria, except that endotoxin had less effect on pressures during the steady state response and caused a relatively larger increase in lymph clearance of large proteins. We conclude that E. coli endotoxin in sheep causes a long period of increased lung vascular permeability and may have a greater effect on large solute pathways across microvessels than do Pseudomonas bacteria.

Animals↗
PubMed1979

Increased pulmonary vascular permeability follows intracranial hypertension in sheep.

After reviewing the characteristics of neurogenic pulmonary edema, Theodore and Robin suggested that it was probably due to rupture of lung vessels by marked but transitory pulmonary hypertension. In this study, we have determined the effects of increased intracranial pressure in a sheep model in which we could measure the flow rate and protein content of lung lymph, and thus detect changes in pulmonary vascular permeability. We found that increasing intracranial pressure to amounts near systemic arterial pressure produced a 3-fold increase in the flow of protein-rich lymph, which indicates increased lung vascular permeability. The high permeability often developed, and always persisted, without extraordinary increases in pulmonary vascular pressure. We conclude that increased lung vascular permeability may follow intracranial hypertension and that extreme pulmonary hypertension is not a prerequisite. Our data do not permit us to exclude barotrauma to exchanging vessels as a cause of capillary damage, but do suggest that other factors, perhaps local release of permeability mediators, may be involved.

Animals↗
PubMed1979

Effects of prostaglandin cyclic endoperoxides on the lung circulation of unanesthetized sheep.

Although prostaglandins E(2) and F(2alpha) have been suggested as mediators of the pulmonary hypertension seen after endotoxin infusion or during alveolar hypoxia, their precursors, the endoperoxides (prostaglandins G(2) and H(2)) are much more potent vasoconstrictors in vitro. In this study we compared the effects of prostaglandin (PG)H(2), a stable 9-methylene ether analogue of PGH(2) (PGH(2)-A), PGE(2), and PGF(2alpha) on pulmonary hemodynamics in awake sheep. The animals were prepared to allow for measurement of (a) lung lymph flow; (b) plasma and lymph protein concentration; (c) systemic and pulmonary vascular pressures; and (d) cardiac output. We also determined the effect of prolonged PGH(2)-A infusions on lung fluid balance and vascular permeability by indicator dilution methods, and by assessing the response of lung lymph. Both PGH(2) and PGH(2)-A caused a dose-related increase in pulmonary artery pressure: 0.25 mug/kg x min tripled pulmonary vascular resistance without substantially affecting systemic pressures. Both were 100 times more potent than PGE(2) or PGF(2alpha) in this preparation. PGH(2)-A, as our analysis of lung lymph and indicator dilution measurements show, does not increase the permeability of exchanging vessels in the lung to fluid and protein. It does, however, augment lung fluid transport by increasing hydrostatic pressure in the pulmonary circulation. We conclude: (a) that PGH(2) is likely to be an important mediator of pulmonary vasoconstriction; (b) its effects are probably not a result of its metabolites PGE(2) or PGF(2alpha).

Animals↗
PubMed1979

Lung vascular permeability: inferences from measurements of plasma to lung lymph protein transport.

In chronically instrumented unanesthetized sheep, we measured steady-state hemodynamic and lung lymph responses to mechanically increased pressure and to intravenous infusions of histamine, Pseudomonas bacteria and E. coli endotoxin. Histamine, Pseudomonas bacteria and E. coli endotoxin caused exchanging vessel permeability to increase, as evidenced by high flows of protein rich lung lymph. This contrasts to the effects of increased pressure where lymph protein concentration falls as lymph flow increases. Microvascular sieving of proteins less than 100 Angstrom radius persisted in all increased permeability states, but with endotoxin, lymph clearance of larger proteins increased much more than with histamine or Pseudomonas. We compared several approaches to quantitative interpretations of lymph data and found that direct methods for calculating permeability-surface area products and reflection coefficients for proteins produced values which were difficult to interpret, probably because fundamental assumptions of the methods were violated in our experiments. A mathematical model based on multiple pore theory produced more plausible coefficients.

Animals↗
PubMed1979

Adult respiratory distress syndrome.

Many causes for the adult respiratory distress syndrome (ARDS) have been reported, all with common pathologic, pathophysiologic and biochemical end results. The final common pathway may involve changes in lung content of a critical enzyme, superoxide dismutase, or alterations in surfactant metabolism, or both. The early assumption that the disorder is partially due to oxygen toxicity from inspired oxygen concentrations greater than 60 percent is consistent with findings of recent biochemical studies. Although the lung normally maintains its alveoli dry, during ARDS increased permeability of small pulmonary vessels results in primary pulmonary edema, in contrast to edema from increased vascular pressure. These data have been obtained mainly in animals; whether they apply to humans with ARDS is not certain. Tissue oxygenation is improved by increasing end-expiratory pressure in an animal model of ARDS, more effectively during spontaneous breathing than during mechanical ventilation. During spontaneous breathing, adverse ventilatory effects were caused by stimulation of pulmonary reflexes.

Humans↗
PubMed1979

Equilibration of intravascular albumin with lung lymph in unanesthetized sheep.

In 16 unanesthetized sheep with chronic lung lymph fistulas we measured pulmonary vascular pressures, lymph flow, lymph and plasma total protein and albumin concentration. We determined the rate of equilibration of radioiodinated albumin between plasma and lung interstitial fluid (lung lymph) in three steady-state conditions; baseline (n = 14), increased pulmonary microvascular pressure (n = 9) and increased microvascular permeability (n = 4). The tracer protein equilibration proceeded according to single compartment wash-in kinetics in all experiments. Lung lymph flow averaged 5.3 +/- 2.8 (S.D.)ml/h under baseline conditions, 16.1 +/- 10.6 ml/h during increased pressure and 37.3 +/- 29.4 ml/h during increased permeability. The half time of equilibration averaged 2.9 +/- 1.0 h, 2.2 +/- 1.0 h and 0.7 +/- 0.2 h, respectively. Lung interstitial fluid equilibrates with plasma proteins more rapidly than most other organs. The marked difference between increased permeability and the other conditions demonstrates the sensitivity of this method. No evidence was obtained that any tracer protein entered lung lymph within the caudal mediastinal lymph node.

Animals↗