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Biomedical subjects

N C Staub

Publications and source records attributed to N C Staub.

At least 73 records · Page 4Linked to original sources
PubMed1986

Sequence of perivascular liquid accumulation in liquid-inflated dog lung lobes.

The peribronchovascular interstitium of the lung is a potential space that expands in pulmonary edema with the formation of large liquid cuffs. To study the time course of cuff formation we inflated nine isolated dog lung lobes with liquid to total lung capacity, rapidly froze them in liquid N2 after inflation periods of 1-300 min, then photographed 20 blocks of each lobe at X3 magnification. From the photographs we measured the ratio of cuff area to vessel area for arteries and veins of 0.05-8 mm diam. We found that the cuff-to-vessel area ratio attained a maximum value of 3-4, which was independent of vessel size. However, the first cuffs to reach maximum size were those around vessels of 0.1-0.5 mm diam, whereas cuffs around larger vessels filled more slowly. No cuffs were visible around vessels smaller than 0.1 mm diam. After 45 min cuffs had formed around 99% of all vessels larger than 0.5 mm diam but had formed around only 38% of veins and 91% of arteries of smaller diameter. We simulated the observed rate and pattern of cuff growth using electrical analog models. The filling pattern and model analyses suggest that liquid entered the interstitium from an air space site associated with arteries of approximately 0.1-1.0 mm diam, spread to adjacent sites, and eventually reached the lobe hilum. The estimated perivascular interstitial flow resistance decreased approximately 100-fold with cuff expansion.

Animals↗
PubMed1986

Effects of plasmapheresis and of hypoproteinemia on lung liquid conductance in awake sheep.

The Starling equation, which describes net transvascular liquid flow, does not include the possibility that a reduction in plasma protein concentration may have a direct effect on lung liquid conductance or microvascular protein permeability. Nevertheless, both effects have been reported. Since these results were not predictable, we wondered whether the changes were due to the decrease in plasma protein concentration or to the process by which protein depletion was accomplished (batch plasmapheresis which involves considerable handling of blood). To separate these factors, we did control (sham) and protein removal plasmapheresis in awake sheep by two plasmapheresis methods (batch and continuous-flow). We monitored pulmonary hemodynamics, measured lung lymph flow, and determined protein concentrations in lymph and plasma. We calculated or measured the protein osmotic pressures of plasma and lymph. After control plasmapheresis, lymph flow increased and lymph:plasma protein concentration decreased but had returned to baseline levels by 4 hours. After protein removal plasmapheresis, the changes persisted for 24 hours. However, lung microvascular conductance (filtration coefficient) was not increased, except during the first 4-hour period. The changes in lymph flow and protein concentration ratio are explained using a simple two-pore model. We conclude that, over the range studied, hypoproteinemia does not increase lung microvascular liquid conductance or protein permeability.

Animals↗
PubMed1986

Thromboxane and prostacyclin in acute lung injury caused by venous air emboli in unanesthetized sheep.

In 4 unanesthetized sheep with lung lymph fistulas we studied the role of thromboxane A2 (TxA2) in the lung microvascular injury caused by 4 h of venous air embolism. In each sheep, we did paired air embolism experiments: control and after giving the TxA2-synthetase inhibitor, U63,557A. Inhibition of TxA2-synthetase did not affect the hemodynamic response to air emboli; lung lymph flow increased slowly but to the same final rate as with air alone. The pulmonary production of TxA2, estimated as the lymph concentration of thromboxane B2 (TxB2) X lymph flow, increased during air embolism in the control experiment but increased much less when TxA2-synthetase was inhibited. Similarly, prostacyclin (PGI2) production increased during air embolism but was reduced when TxA2-synthetase was inhibited. Our results suggest that TxA2 does not mediate the pulmonary hypertension caused by venous air emboli, but it might modulate the increase in lymph flow by acting on the lymphatic pump or affecting hemodynamics in the pulmonary microcirculation. Our results do not support that TxA2 mediates the injury caused by venous air embolism. Pulmonary production of PGI2 seems to depend on the pulmonary production of TxA2, as shown by the parallel changes of their metabolites during air embolization.

Animals↗
PubMed1985

Blood supply of the caudal mediastinal lymph node in sheep.

We investigated the arterial supply to, and the venous drainage from, the caudal mediastinal lymph node (CMN) in 18 anesthetized and exsanguinated sheep. The purpose of this gross anatomic investigation was to determine the CMN's blood supply so that a structural base can be used to interpret studies of the bronchial circulation's role in the pathogenesis of pulmonary edema. In ten sheep, we cannulated the bronchoesophageal artery at its origin from the aorta and injected Microfil. This artery, which branches into cranial and caudal divisions 2-4 mm distal to its origin, supplied the esophagus, trachea, bronchi, and visceral pleura. The CMN is supplied by the caudal division, as it courses between the CMN and aorta. Microfil injected through the thoracic aorta did not enter the CMN when the bronchoesophageal artery was ligated at its origin. These results indicate that only the bronchoesophageal artery supplies the CMN. In eight sheep we cannulated the vein at the head of the CMN (dorsal mediastinal vein) and injected Microfil, both peripherally and centrally. Peripherally, injected veins reached the CMN and esophagus. The dorsal mediastinal vein extended posteriorly to the CMN in three of the eight sheep, eventually emptying into the left azygos vein near the diaphragm. Centrally, the dorsal mediastinal vein joined the left azygos vein near the heart in six of the eight sheep, including the three in which the dorsal mediastinal vein extended posteriorly to the CMN. In the remaining two sheep the dorsal mediastinal vein drained centrally into the right azygos vein. We conclude that the bronchoesophageal artery supplies the CMN and that either the left or right azygos vein drains it.

Animals↗
PubMed1985

Long-term clearance of liquid and protein from the lungs of unanesthetized sheep.

We measured the removal of 100 ml of autologous serum from the air spaces and lungs of unanesthetized, spontaneously breathing sheep at 4, 12, and 24 h. In the first 4 h, there was a rapid clearance of the liquid volume (8.3%/h), similar to our results in anesthetized ventilated sheep (Matthay et al., J. Appl. Physiol. 53: 96-104, 1982). However, liquid removal progressively slowed to 3.3 and 1.4%/h at 12 and 24 h, respectively. In contrast, protein clearance (as measured by 125I-albumin instilled with the serum) was monoexponential and slow (1%/h). The slowing of liquid clearance appears to be a function of the rising protein osmotic pressure of the residual protein in the air spaces (protein concentration doubled in 24 h). Because protein solutions are chemotactic for neutrophils, we quantified the movement of liquid from the extracellular space into the alveolar compartment with a plasma protein tracer (131I-albumin), so that our final calculation of alveolar liquid clearance would take into account bidirectional movement of liquid across the alveolar barrier. The corrected values for net liquid clearance are slightly faster (less than 10% of the instilled volume).

Animals↗
PubMed1985

Relationship of pleural effusions to pulmonary hemodynamics in patients with congestive heart failure.

On the basis of both experimental and clinical studies it is not clear whether left, right, or biventricular heart failure are necessary for the formation of pleural effusions. In order to study the relationship of pulmonary hemodynamics and the presence of pleural effusions in patients with congestive heart failure, we prospectively evaluated 37 patients admitted to the coronary care unit with congestive heart failure secondary to ischemic heart disease or a cardiomyopathy. We used real-time ultrasonography to document the presence of pleural effusions. We found that 19 of the 37 patients with heart failure had pleural effusions. Mean pulmonary artery wedge pressure was 24.1 +/- 1.3 mmHg (SE) in the 19 patients with pleural effusions versus 17.2 +/- 1.5 mmHg (SE) (p less than 0.001) in the 18 patients without pleural effusions. Pulmonary artery pressure was also higher in patients with pleural effusions with a mean value of 38.0 +/- 1.5 mmHg (SE) versus 30.7 +/- 2.1 mmHg (SE) (p less than 0.05) in the patients without pleural effusions. In contrast, mean right atrial pressure was not different between patients with pleural effusions (12.6 +/- 1.5 mmHg) (SE) versus those without pleural effusions (9.8 +/- 1.0 mmHg) (SE) (p = NS). In addition, there was no difference in cardiac output, pulmonary vascular resistance, or total protein concentrations between patients with and without pleural effusions. We conclude that, in patients with congestive heart failure, an elevated left atrial pressure is closely correlated with the presence of pleural effusions, while concurrent elevation of right atrial pressure is not associated with the presence of pleural effusions.

Blood Pressure↗
PubMed1985

Effect of neutrophil migration induced by leukotriene B4 on protein permeability in sheep lung.

Although several types of acute lung microvascular injury require active participation of circulating leukocytes (presumably neutrophils), the relationship between neutrophils and microvascular injury and edema is controversial. We attempted to answer the question, Does neutrophil migration in response to a chemical signal alter endothelial permeability? If so, is this to be regarded as a significant control mechanism for microvascular protein permeability? Because of our interest in pulmonary injury, we attempted to induce neutrophil chemotaxis into the lungs of anesthetized sheep by using leukotriene B4 (LTB4) (2 nmol/ml, 50 ml total) placed in the alveoli of one caudal lung lobe through a fiberoptic bronchoscope. Measurements of pulmonary hemodynamics, lymph dynamics, and alveolar liquid dynamics were made. Compared to chemotaxis into skin, neutrophil migration into alveoli was slow. LTB4 caused a small increase in lung lymph and protein flow, which was slightly more than that in saline controls. Likewise, excess plasma protein entering the alveolar liquid was slightly increased over saline controls. Both results indicate a small increase in liquid and protein flow across the endothelial and alveolar epithelial barriers in response either to the LTB4 or to the neutrophil chemotaxis. Using a worst case analysis, the slight increase in liquid and protein flow across the endothelium and epithelium may be related to quantal leakage of plasma during neutrophil transit, but there is no evidence for any persistent change in microvascular or epithelial permeability.

Animals↗
PubMed1984

The structure of the parietal pleura and its relationship to pleural liquid dynamics in sheep.

We studied the parietal pleura of six sheep to obtain information on pleural structure, blood supply, and lymphatic drainage. In the strict sense, the parietal pleura is composed of a single layer of mesothelial cells and a uniform layer of loose, irregular connective tissue (about 23 micron in width) subjacent to the mesothelial cells. The parietal pleural blood vessels are 10-15 micron from the pleural space. Tracer substances put in the pleural space are removed at specific locations. Colloidal carbon and chick red blood cells are cleared by the parietal pleural lymphatics located over the intercostal spaces at the caudal end of the thoracic wall and over the lateral sides of the pericardial sac. In these areas the mesothelial cells have specialized openings, the stomata, that directly communicate with the underlying lymphatic lacunae. Cells and particulate matter in the pleural space are cleared only by the parietal pleural lymphatics. Compared to the visceral pleura, we believe the thinness of the parietal pleura, the closeness of its blood vessels to the pleural space, and its specialized lymphatic clearance pathways, together indicate that the parietal pleura plays a major role in pleural liquid and protein dynamics in sheep.

Animals↗
PubMed1984

Interstitial fluid pressure gradient measured by micropuncture in excised dog lung.

We have directly measured lung interstitial fluid pressure at sites of fluid filtration by micropuncturing excised left lower lobes of dog lung. We blood-perfused each lobe after cannulating its artery, vein, and bronchus to produce a desired amount of edema. Then, to stop further edema, we air-embolized the lobe. Holding the lobe at a constant airway pressure of 5 cmH2O, we measured interstitial fluid pressure using beveled glass micropipettes and the servo-null method. In 31 lobes, divided into 6 groups according to severity of edema, we micropunctured the subpleural interstitium in alveolar wall junctions, in adventitia around 50-micron venules, and in the hilum. In all groups an interstitial fluid pressure gradient existed from the junctions to the hilum. Junctional, adventitial, and hilar pressures, which were (relative to pleural pressure) 1.3 +/- 0.2, 0.3 +/- 0.5, and -1.8 +/- 0.2 cmH2O, respectively, in nonedematous lobes, rose with edema to plateau at 4.1 +/- 0.4, 2.0 +/- 0.2, and 0.4 +/- 0.3 cmH2O, respectively. We also measured junctional and adventitial pressures near the base and apex in each of 10 lobes. The pressures were identical, indicating no vertical interstitial fluid pressure gradient in uniformly expanded nonedematous lobes which lack a vertical pleural pressure gradient. In edematous lobes basal pressure exceeded apical but the pressure difference was entirely attributable to greater basal edema. We conclude that the presence of an alveolohilar gradient of lung interstitial fluid pressure, without a base-apex gradient, represents the mechanism for driving fluid flow from alveoli toward the hilum.

Animals↗
PubMed1984

Protein egress and entry rates in pleural fluid and plasma in sheep.

We determined a rate of protein egress from the pleural cavity into thoracic duct lymph in seven anesthetized sheep in whom we had made 10-ml/kg hydrothoraces containing 1% plasma protein labeled with 125I-albumin. The labeled protein left the pleural space at an average rate of 0.02 ml X kg-1 X h-1. In 25 unanesthetized sheep we injected labeled protein intravenously and collected pleural fluid and plasma at intervals up to 48 h. The radioactivity in the sheeps' plasma fell twice as rapidly as the rate observed in humans. The half time for equilibration between plasma and pleural fluid protein specific activity was approximately 6 h. In seven sheep we gave a continuous infusion of tracer protein. In six of these seven sheep we collected superficial cervical lymph. The protein concentration in the lymph was three times that of pleural fluid. The half time for protein specific activity equilibration between plasma and pleural fluid was 5 h and 3-4 h between plasma and superficial cervical lymph. The rate of protein turnover in the pleural space appears to be much slower than previously reported.

Anesthesia, General↗
PubMed1984

Quantification of damage by air emboli to lung microvessels in anesthetized sheep.

We studied the ultrastructural damage caused by venous air embolization in anesthetized sheep by morphological techniques after monitoring hemodynamics and lymph dynamics. Lung lymph flow and protein flux increased during 1 and 4 h of venous air embolization, results consistent with increased microvascular permeability. Histologically, the air emboli were restricted to the small pulmonary arterial vessels (1,000 to 100 micron in diam). Neutrophils accumulated around the air bubbles and formed intravascular clumps. Ultrastructurally, at the air embolus-blood interface, neutrophils appeared attached to a layer a proteinaceous material. Many neutrophils were in close contact with the pulmonary arterial endothelial cells. We found gaps (0.1-3 micron in width) between the endothelial cells of the pulmonary arterial microvessels. Beneath these gaps the basal lamina was disrupted. Other vessel types were unaffected. Some lymphocytes were seen near the air bubbles and the endothelial cell gaps. Platelets remained discoid, and fibrin clots were not observed. These results indicate that venous air embolization in sheep damages the pulmonary arterial microvessels. Neutrophils are closely associated to both the air emboli and the endothelial cell gaps.

Anesthesia, General↗
PubMed1984

Micropuncture measurement of lung microvascular pressure profile during hypoxia in cats.

To determine the lung microvascular pressure profile during hypoxia, we micropunctured the subpleural microcirculation of isolated perfused cat lungs. Our procedures involved exsanguinating a cat, then cannulating its pulmonary artery, left atrium, and trachea. Using the cat's own blood, we perfused the lungs at pulmonary artery and left atrial pressures of 18 and 9 cm water, respectively, to obtain lung blood flow of 81 +/- 29 ml/(kg body weight x min), which we held constant throughout the experiment. We stabilized the lung surface with a vacuum ring and micropunctured 30- to 50-micrometers arterioles and venules to measure microvascular pressure by the servo-null method. During micropuncture, we held the lungs at constant inflation using airway pressure of 8 cm water. We varied the oxygen concentration of the inflation gas from 30% during baseline to 2% during hypoxia. We studied groups with high (more than 7.5) or normal pH. During normoxia, 27, 44, and 29% of the pressure drop occurred in the arterial, capillary and venous segments, respectively. During hypoxia, the increase in pulmonary vascular resistance, which was marked in both groups, was significantly greater in the normal pH group. All segmental pressure drops increased significantly during hypoxia. However, the predominant increase occurred in the arteries where segmental pressure drop increased by 148% and 210%, respectively, in the high and normal pH groups. We conclude that the major site of hypoxic vasoconstriction is in the pulmonary arteries.

Acid-Base Equilibrium↗
PubMed1983

The measurement of lung water content.

It is clear that lung water content or things related to lung water content can be measured. The major question is whether useful information will be obtained to make development worthwhile. In my experimental laboratory we have used, then abandoned, the measurement of lung water content in life by various techniques. We have special needs, of course, for very sensitive methods which will detect minimal injury and very small changes in lung water content. In the clinic, however, this may not be so serious a limitation, although one is always endeavoring to achieve diagnosis of minimal injury and minimal edema. Although static methods for measuring lung water content are available in profusion, none has been proven to be more useful than the chest roentgenogram. Kinetic methods are being developed which have the potential of being sensitive to minimal lung injury, such as leads to edema.

Animals↗