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Biomedical subjects

N C Staub

Publications and source records attributed to N C Staub.

At least 91 records · Page 5Linked to original sources

Removal of abdominal sources of caudal mediastinal node lymph in anesthetized sheep.

We investigated the conditions for and the quantity of abdominal contributions to caudal mediastinal node (CMN) efferent lymph in 15 anesthetized sheep with open thorax and lung lymph fistulas. Contractions of the diaphragm by phrenic nerve stimulation increased lymph flow by 29%. Adding large volumes (10 ml/kg) of 5% albumin solution to the peritoneal cavity increased lymph flow by 19 and 28% during diaphragm contraction. Tracer albumin specific activity in lymph indicated that about half the lymph flow increment came from the peritoneal liquid. Raising hepatic vein pressure 19 cmH2O increased CMN lymph flow 178%. Lymph protein concentration also increased markedly, from 0.72 to 0.91 of the plasma concentration. We devised a simple procedure to cauterize across the pleural surface of the diaphragm to destroy the aberrant lymphatics. This procedure markedly diminished both abdominal cavity and portal system contributions.

Abdomen↗

Effect of lung inflation on alveolar-airway barrier protein permeability in dog lung.

To determine the leakiness to protein of the barrier that separates the air space and interstitial compartment of the lung, we measured perivascular interstitial fluid cuff protein concentration and volume in 10 isolated and 9 intact closed-chest dog lung lobes, which we degassed and inflated to 25, 50, 75, or 100% of capacity with 5% bovine serum albumin labeled with Evans blue dye. After 1 h we froze the lobes in liquid N2 and made color transparencies of 20 randomly selected frozen samples of each lobe. We measured Evans blue dye-albumin concentrations from absorption by cuff images of a 50-micron-diam red (lambda = 620 nm) microspot. We measured absolute cuff volume (ml/g dry lung) by point counting on the transparencies. Using specific Evans blue-albumin fluorescence we determined that the dye was protein bound in airways and cuffs. Cuff protein concentration averaged 37% of instillate concentration and did not vary with inflation volume or between isolated and intact lobes. Cuff volume was 3.4 ml/g dry lung at total lung capacity in both isolated and intact lobes. We conclude that at some point the barrier is permeable to albumin as well as liquid at all lung volumes in dogs and that the protein sieving properties of the barrier do not change with lung expansion over the range examined. The liquid storage capacity of the cuffs can increase as much as 20-fold between low and high lung volumes.

Albumins↗

Superoxide dismutase with heparin prevents increased lung vascular permeability during air emboli in sheep.

We studied the effects of bovine superoxide dismutase on the increased lung microvascular permeability to fluid and protein during air emboli in unanesthetized sheep. We measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and lymph and plasma protein concentrations. In air emboli experiments we continuously infused the same dose of air bubbles 1 mm in diameter into the right atrium of each sheep to increase pulmonary vascular resistance to 2-4 times base-line values. We did experiments in pairs so that each sheep served as its own control. We found an increase in protein-rich lymph flow from the lung during embolization in untreated sheep, indicating an increase in microvascular permeability to both fluid and protein. When we pretreated the sheep with heparin (300 U/kg) and infused them with intravenous bovine superoxide dismutase (1 mg X kg-1 X h-1 beginning before the air infusion), we found that vascular pressures and pulmonary vascular resistance were not different from untreated sheep but that the expected increases in transvascular fluid and protein flow during emboli were significantly decreased (P less than 0.0005). Heparin alone did not significantly attenuate the increased microvascular permeability but we found that it greatly enhanced the effectiveness of superoxide dismutase in preserving microvascular functional integrity during air emboli. We conclude that superoxide anion, probably produced and released by leukocytes, is a central factor in the microvascular injury that results in increased permeability in the lungs of sheep during air microembolization.

Animals↗

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

Overperfusion (high pressure and flow through a restricted microvascular bed) has been suggested as the mechanism for both microembolic and high altitude pulmonary edema. In eighteen anesthetized, ventilated sheep, we measured pulmonary hemodynamics, lung lymph flow, and lymph:plasma protein concentration ratio. After a 2-hour stable baseline, we resected 65% of lung mass (right lung and left upper lobe) and gave whole blood transfusions to maintain cardiac output. During overperfusion of the left lower lobe, lymph flow increased moderately (5.8 +/- 2.3 to 7.7 +/- 3.8 ml/hr) and lymph:plasma protein concentration decreased (0.73 +/- 0.08 to 0.64 +/- 0.08). After a 2-hour stable period, we decreased inspired oxygen in 10 sheep (Pao2 = 40 +/- 3 mm Hg). With added alveolar hypoxia, pulmonary artery pressure increased modestly, but lymph flow and the lymph:plasma protein concentration ratio did not change. In eight sheep (four hypoxic, four normoxic), we raised left atrial pressure approximately 12 cm H2O for 2 hours. Lymph flow rose (10.8 +/- 3.8 ml/h) and lymph:plasma protein concentration decreased further (0.52 +/- 0.07). At each step, lymph:plasma protein concentration decreased, as predicted for the calculated rise in microvascular pressure. There was no evidence that overperfusion, with or without alveolar hypoxia, increased lung endothelial barrier protein permeability.

Animals↗

Concentrated albumin does not affect lung edema formation after acid instillation in the dog.

Recent investigations of the role of large infusions of concentrated serum albumin on the acute pulmonary edema caused by hydrochloric acid (HCl) aspiration have produced contradictory results. We used the open thorax anesthetized dog with weighed lung lobe as well as completely isolated perfused weighed lobes. The results were the same with both preparations. Instillation of 0.1 N HCl (2 ml/kg) caused small increases in pulmonary artery pressure, and the rate of lung weight gain increased from 1.2 to 2.5 g/h to 22.2 to 30.2 g/h. Addition of 25% human serum albumin, either before or after acid instillation, had no significant effect on the rate of lobe weight gain. Additional experiments showed that after HCl the rate of lobe weight gain was exquisitely sensitive to pulmonary arterial pressure. Albumin therapy is without benefit in the prevention or treatment of the pulmonary edema caused by HCl aspiration.

Animals↗

Recent developments in pulmonary edema.

Research on lung fluid balance and pulmonary edema has increased during the last decade. New approaches have led to insights into the role of each component of the alveolar-capillary barrier. The capillary endothelium is the first line of defense against lung fluid accumulation. The interstitium may play a more important role in lung fluid balance than previously appreciated. Active and passive transport properties of alveolar epithelium may be important in the pathogenesis and resolution of alveolar edema. New methods for the determination of epithelial permeability and lung water are being evaluated. The developments reviewed here may have an impact on the institution of new diagnostic and therapeutic approaches to pulmonary edema during the next decade.

Animals↗

Structure, blood supply, and lymphatic vessels of the sheep's visceral pleura.

We investigated the morphology of the visceral pleura of 36 sheep, using macroscopic, histologic, and ultrastructural approaches to quantify regional pleural thickness, blood supply, and lymphatic drainage, including the pulmonary ligament and hilar lymphatic distributions. Pleural thickness increased caudally and dorsally, such that the costal pleura of the caudal lobes had a mean minimum pleural thickness of 83 microns. The blood supply to the entire visceral pleura came exclusively from the bronchial arteries. Lymph vessels formed an extensive plexus throughout the serous membrane of all lobes. Trunk lymphatics (greater than 100 microns diameter) had a density of about 2/cm of pleural length on all lobar surfaces except for the cranial and middle lobes, where their density on the costal surfaces was less than 1/cm. Pleural trunk lymphatics coursed to the pulmonary ligaments and to the hilum on their way to regional lymph nodes. At the hilum they anastomose with intrapulmonary lymphatic trunks. The principal lymph nodes to receive pulmonary lymph were the caudal mediastinal node and tracheobronchial nodes. The visceral pleura of sheep is thick, showing considerable regional diversity in morphology.

Animals↗

Micropuncture measurement of lung microvascular pressure during 5-HT infusion.

We punctured subpleural microvessels in 19 isolated blood-perfused dog lung lobes to determine the effect of 5-hydroxytryptamine (5-HT) on the pulmonary microvascular pressure profile. Maintaining lobe airway pressure at 6 cmH2O and lobe venous pressure at 10 cmH2O we infused saline alone (10 microliter/min) in 10 control lobes and 5-HT in saline solution (100--150 micrograms/min) in 9 lobes. We measured pressures in subpleural microvessels using micropipettes connected to a servo-null system. The 5-HT infusion doubled lobar vascular resistance. In all microvessels upstream from the 150-micrometer venules, pressure was higher than in the control lobes. In contrast to the control lobes, pressure dropped markedly from the lobar artery to the 50-micrometer arterioles and from the venous capillaries to the 50-micrometer venules. We conclude that 5-HT not only constricted arterioles, but also raised lung microvascular pressure by constricting postcapillary venules.

Animals↗

Differential liquid and protein clearance from the alveoli of anesthetized sheep.

We determined the clearance rates of 50 ml of isosmotic fluids from the lungs of anesthetized, ventilated sheep with lung lymph fistulas. The removal of the liquid volume followed a monoexponential process over 4 h for both Ringer lactate [half time (t 1/2) = 3 h] and autologous serum (t 1/2 = 6 h). Lymph flow did not increase with Ringer lactate, indicating that the alveolar fluid was cleared via the circulation. With serum, however, lymph flow increased 40%. In both groups the lymph-to-plasma protein concentration ratio fell slightly. Using protein tracers in the alveolar instillate, we found that less than 2% of the protein entered the lymph and plasma. Almost all of the protein remained in the air spaces and was concentrated in proportion to the amount of liquid volume that was cleared. Clearance of liquid volume from alveoli to interstitium could be due to subatmospheric interstitial fluid pressure or to active metabolic processes that cause small molecules to leave the alveolar fluid, or both. The results of the serum experiments tend to favor a metabolic process, but passive mechanisms are possible. The difference in lymph flow response between the two fluids must be due to the protein in the alveolar fluid. We believe Ringer lactate dilutes the alveolar wall interstitial protein concentration thereby decreasing local filtration, whereas serum concentrates alveolar wall interstitial fluids proteins thereby increasing local filtration.

Anesthesia↗

Anatomic variations of efferent duct from caudal mediastinal lymph node in sheep.

Collection of lymph from the efferent duct of the caudal mediastinal node in sheep is accepted as a reliable method for following lung microvascular fluid and protein filtration. There are significant variations in the efferent duct anatomy, which can complicate the cannulation procedure and, therefore, the success of the preparations. We analyzed the major variations in the efferent duct in 75 consecutive sheep. The majority (59%) had a single efferent duct varying in length, course, and origin fom the caudal mediastinal node; 41% had multiple ducts, often with confluences or bifurcations, making successful cannulation more difficult. It is important to recognize the potential variations in the efferent duct to facilitate useful cannulation.

Animals↗