Overperfusion, hypoxia, and increased pressure cause only hydrostatic pulmonary edema in anesthetized sheep.

Landolt, Cleland C.; Matthay, Michael A.; Albertine, Kurt H.; Roos, Philip J.; Wiener-Kronish, J. P.; Staub, Norman C.

doi:10.1161/01.res.52.3.335

Cited by 52 publications

(19 citation statements)

References 20 publications

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“…There was a mean increase of 7 cm H20 in the calculated pulmonary microvascular pressure in the oleic acid studies, based primarily on a rise in pulmonary arterial pressure. Therefore, we studied two sheep in which left atrial pressure was increased by 7 cm H20 with a left atrial balloon, as we have done before (14), and then instilled serum into one lower lobe. The same variables were measured as in the other experiments.…”

Section: Specific Protocolsmentioning

confidence: 99%

Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin.

Wiener-Kronish¹,

Albertine²,

Matthay³

1991

J. Clin. Invest.

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309

204

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Although intravenous Escherichia coli endotoxin has been used extensively in experimental studies to increase lung endothelial permeability, the effect of E. coli endotoxin on lung epithelial permeability has not been well studied. To examine this issue in sheep, bidirectional movement ofprotein across the lung epithelial barrier was studied by labeling the vascular space with 13"I-albumin and-by instilling 3 ml/kg of an isosmolar protein solution with`-I-albumin into the alveoli. E. coli endotoxin was administered according to one of three protocols: intravenous alone (5-500 ug/kg), intravenous (5 pg/kg) plus low-dose alveolar endotoxin (10 pg/kg), and high-dose alveolar endotoxin alone (50-100 pg/kg). Alveolar liquid clearance was estimated based on the concentration of the instilled native protein.Sheep were studied for either 4 or 24 h. Although intravenous E. coli endotoxin produced a marked increase in transvascular protein flux and interstitial pulmonary edema, there was no effect on the clearance of either the vascular ("3'I-albumin) or the alveolar (1251-albumin) protein tracer across the epithelial barrier. High-dose alveolar E. coil endotoxin caused a 10-fold increase in the number of leukocytes, particularly neutrophils, that accumulated in the air spaces. In spite of the marked chemotactic effect of alveolar endotoxin, there was no change in the permeability of the epithelial barrier to the vascular or alveolar protein tracers. Also, alveolar epithelial liquid clearance was normal. Morphologic studies confirmed that the alveolar epithelial barrier was not injured by either intravenous or alveolar E. coli endotoxin. Thus, the alveolar epithelium in sheep is significantly more resistant than the lung endothelium to the injurious effects of E. coli endotoxin. (J. Clin. Invest. 1991. 88:864-875.) Key words: E. coli endotoxin * alveolar epithelium -lung endothelium * alveolar liquid clearance * acute lung injury

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Section: Specific Protocolsmentioning

confidence: 99%

Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin.

Wiener-Kronish¹,

Albertine²,

Matthay³

1991

J. Clin. Invest.

Self Cite

309

204

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“…Elegant studies using sheep have previously demonstrated that acute increases in PBF or pressure led to increased capillary filtration of protein-poor fluid and augmented clearance of lymphatic fluid (12,19,42,44,50). However, infants born with congenital cardiac defects often live with increased PBF for months or years before their defects are surgically corrected, and it remains unknown what effect this chronically increased PBF has on the function and structure of the pulmonary lymphatic system.…”

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confidence: 99%

Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow

Datar¹,

Johnson

Oishi

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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Abnormalities of the lymphatic circulation are well recognized in patients with congenital heart defects. However, it is not known how the associated abnormal blood flow patterns, such as increased pulmonary blood flow (PBF), might affect pulmonary lymphatic function and structure. Using well-established ovine models of acute and chronic increases in PBF, we cannulated the efferent lymphatic duct of the caudal mediastinal node and collected and analyzed lymph effluent from the lungs of lambs with acutely increased PBF ( n = 6), chronically increased PBF ( n = 6), and age-matched normal lambs ( n = 8). When normalized to PBF, we found that lymph flow was unchanged following acute increases in PBF but decreased following chronic increases in PBF. The lymph:plasma protein ratio decreased with both acute and chronic increases in PBF. Lymph bioavailable nitric oxide increased following acute increases in PBF but decreased following chronic increases in PBF. In addition, we found perturbations in the transit kinetics of contrast material through the pleural lymphatics of lambs with chronic increases in PBF. Finally, there were structural changes in the pulmonary lymphatic system in lambs with chronic increases in PBF: lymphatics from these lambs were larger and more dilated, and there were alterations in the expression of vascular endothelial growth factor-C, lymphatic vessel endothelial hyaluronan receptor-1, and Angiopoietin-2, proteins known to be important for lymphatic growth, development, and remodeling. Taken together these data suggest that chronic increases in PBF lead to both functional and structural aberrations of lung lymphatics. These findings have important therapeutic implications that warrant further study.

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“…In contrast to our results with preterm lambs and a PDA, L:P increased as lymph flow increased in lambs with pulmonary oxygen toxicity. In studies performed with adult sheep that had almost two thirds of their total lung mass resected, Landolt et al (6) did not detect any evidence of increased lung vascular permeability, despite the fact that the entire cardiac output of these sheep flowed through only a small fraction of the pulmonary vascular bed. Thus, we think that increased blood flow to the lungs through a PDA, even in relatively small lungs of preterm lambs, does not cause an increase in pulmonary vascular protein permeability.…”

Section: Discussionmentioning

confidence: 96%

“…PC was calculated using Gaar's equation (5) in the form PC = PLvED + 0.4 (PpA -PLVED). This equation correlates well with capillary pressure as measured by arterial occlusion (5) and has been used in experiments with pulmonary overperfusion (6). Although the assumptions underlying the partition values chosen in this equation may not hold in conditions of very high pulmonary flow, we are using PC as an index of filtration pressure.…”

Section: Abbreviationsmentioning

confidence: 87%

Patent Ductus Arteriosus Increases Lung Fluid Filtration in Preterm Lambs

et al. 1991

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ABSTRACT. Previous studies showed that increased pul-The DA is a fetal vascular channel that normally closes soon monary blood flow from a patent ductus arteriosus had after birth. If it remains patent, as it often does after premature little or no effect on the amount of fluid in the lungs of birth, blood flow from the aorta into the pulmonary artery mechanically ventilated preterm lambs. The purpose of increases as pulmonary vascular resistance decreases postnatally. this study was to examine the effect of a patent ductus A PDA is thus associated with increased pulmonary blood flow, arteriosus on lung vascular permeability and to see whether pulmonary blood pressure, and PLvED (1, 2). The presence of a increased pulmonary lymph flow might compensate for the PDA may cause pulmonary edema in premature infants with increased rate of fluid filtration. Using a model that allows respiratory distress (3,4). However, little information is available mechanical control of ductus patency, we studied the effects to demonstrate how the PDA adversely affects pulmonary fluid of increased pulmonary blood flow on lung vascular pres-balance. sures in six mechanically ventilated premature lambs at Several studies have examined the effects of increased pulmo-We nary blood flow on lung fluid balance in adult and mature measured lung lymph flow and protein concentrations in newborn animals (5-1 1). In some of these studies, the increase lymph and plasma to assess pulmonary vascular fluid in microvascular fluid filtration associated with increased pulfiltration and protein permeability. We studied each lamb monary blood flow was attributed to increased microvascular during sequential steady state periods, first with the ductus filtration pressure (5, 6, 1 1); in other studies, the increased open and then with it closed. When the ductus was open, filtration was thought to be the result of lung vascular recruitment pulmonary blood flow was twice what it was when the (7-10). There is some evidence that the capacity for vascular ductus was closed. Mean pulmonary artery pressure and recruitment and increased fluid filtration in the pulmonary cirleft ventricular end-diastolic pressure were greater with culation may be age dependent (10-13). Little information is the ductus open [40 +. 5 torr (5.3 f 0.7 kPa) and 8 f 3 available regarding the influence of increased perfusion on lung torr (1.1 f 0.4 kPa), respectively] than when it was closed fluid filtration in the presence of underlying pulmonary pathol-124 f 3 torr (3.2 f 0.4 kPa) and 4 f 2 torr (0.5 f 0.3 ogy (9, 14), and the relationship between blood flow and fluid kPa), respectively]. When the ductus was open, lymph flow dynamics in the immature lung is even more obscure. was 68% greater and lymph protein concentration was 17%We used an animal model of the PDA that enables us to study lower than when the ductus was closed. Lymph protein the effects of increased pulmonary blood flow on lung fluid clearance (lymph flow % lymph protein concentration/ balance in newborn sheep (1,2,15). Pr...

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Overperfusion, hypoxia, and increased pressure cause only hydrostatic pulmonary edema in anesthetized sheep.

Cited by 52 publications

References 20 publications

Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin.

Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin.

Altered lymphatics in an ovine model of congenital heart disease with increased pulmonary blood flow

Patent Ductus Arteriosus Increases Lung Fluid Filtration in Preterm Lambs

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