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Biomedical subjects

N C Staub

Publications and source records attributed to N C Staub.

At least 109 records · Page 6Linked to original sources
PubMed1981

Venous air emboli in sheep: reversible increase in lung microvascular permeability.

We studied the effects of continuous intravenous air embolization on lung fluid balance in unanesthetized sheep. Following a 2-h base line, we infused 300-micrometers-diam air bubbles into the pulmonary artery at a rate sufficient to increase pulmonary vascular resistance by 60-300% and for periods of 0.25-3 h. Air emboli produced a dose- and duration-dependent increase in lung lymph and protein flow due mainly to an increase in endothelial barrier permeability but also to elevated pressure in the over-perfused microcirculation. When we stopped the air infusion, the vascular resistance fell as the air emboli were reabsorbed. Lung lymph and protein flow increased further and then returned slowly to base line with a half-time proportional to the duration of embolization. Increasing left atrial pressure during air embolization caused an increase in lymph flow and protein clearance and an average decrease of 15 Torr in arterial O2 tension, all changes in excess of that caused by either increased pressure or air emboli alone.

Animals↗
PubMed1981

Leukocytes are required for increased lung microvascular permeability after microembolization in sheep.

We studied the effects of uneven pulmonary artery obstruction by microemboli on steady state transvascular fluid and protein exchange in normal and leukopenic sheep. We measured pulmonary artery and left atrial pressures, cardiac output, lung lymph flow, and lymph plasma protein concentrations. Sheep were made profoundly leukopenic by administration of intra-arterial mechlorethamine hydrochloride (0.4 mg/kg, two doses) and colchicine (0.1-0.2 mg/kg, anesthetized sheep only). In anesthetized sheep, we injected glass beads 200 micrometers in diameter via the right atrium to raise pulmonary vascular resistance to 2-3 times baseline values. With normal levels of circulating leukocytes, sheep developed an increased protein-rich lymph flow from the lung characteristic of increased permeability edema. Leukopenic sheep had a significantly attenuated response after embolization for equivalent degrees of vascular obstruction. In unanesthetized sheep, we continuously infused air bubbles 1 mm in diameter via the right atrium to raise pulmonary vascular resistance to about 2 times baseline values. Each sheep served as its own control. With normal circulating leukocyte levels, there was an increase in protein-rich lymph flow from the lung during embolization. When the air infusion ended, the sheep recovered to the baseline condition in 24 hours. We induced emboli with the same amount of air when the sheep were profoundly leukopenic; lymph and protein flow from the lung were significantly less for equivalent degrees of obstruction. We conclude that circulating leukocytes are essential for the microvascular injury that results in increased permeability in the lungs of sheep after microembolization.

Animals↗
PubMed1981

The corrected protein equation to estimate plasma colloid osmotic pressure and its development on a nomogram.

Examining the internal discrepancies of three equations (Landis and Pappenheimer 1965) which represent the relationship between colloid osmotic pressures (COP) and normal human plasma proteins, the authors derived a corrected globulin equation: COPglb = 1.3c + 0.14c2 + 0.006c3 (COP: mmHg, c: protein content, g/100 ml), instead of their COPglb = 1.6c + 0.15c2 + 0.006c3, when A/G (albumin-globulin ratio) = 1.1 as they had described. Revising the former globulin equation again, based upon the current estimate of A/G = 1.8, we derived a new globulin equation. Our new plasma equation, consisting of their albumin equation and our revised globulin equation, is COPpl = alpha (2.8c + 0.18c2 + 0.012c3) + beta (0.9c + 0.12c2 + 0.004c3), where alpha and beta stand for albumin and globulin fraction, respectively. The last, being generalized for plasma with any protein compositions, and closely corresponded to the values directly measured in normal human plasma with variable protein compositions, we developed it on a nomogram for practical use.

Adult↗
PubMed1981

The emerging role of the microcirculation in clinical medicine.

Although research on microcirculation has expanded rapidly in the last 20 years, clinical evaluation of microcirculation, as an entity, has not achieved any status in the United States. Three aspects of microcirculation are presented, wherein clinical applications exist or on the verge of existing. Biomicroscopy is the direct observation of, and measurements within, the microcirculation is superficial areas of the body. Not only can the pattern of the microcirculation be examined and related to microcirculatory function but also the intravascular relationships among red cells, leukocytes, and platelets can be studied. Rheology includes measurement of the interactions among plasma and cellular elements during flow within the microcirculation. Unfortunately, rheologic factors are generally ignored in thinking about hemodynamics. The concept of the optimal hematocrit has great clinical relevance in both acute and chronic disease. Transvascular fluid and solute exchange can be evaluated in the body as a whole and in individual organs by relatively noninvasive techniques. Such evaluations provide useful information about the natural progress and the effect of treatment of a variety of serious diseases. Microcirculation, as an entity, is a quantitative science in its own right and ought to be actively applied in clinical medicine.

Biological Transport↗
PubMed1980

Direct measurement of microvascular pressures in the isolated perfused dog lung.

Microvascular pressures in the pulmonary circulation were measured under the pleural surface of the isolated perfused dog lung by the servo-null technique. Strong glass micropipettes with short beveled tips were used, with a suction ring to stabilize the lung's surface. Of the total vascular resistance, 45 percent was in the alveolar wall capillaries themselves. Most of the remaining resistance was in the arterioles. There was negligible pressure drop in venules with diameters larger than 20 micrometers.

Animals↗
PubMed1980

Conference report of a workshop on the measurement of lung water.

Thirty-five investigators representing the fields of anatomy, anesthesiology, biophysics, chest medicine, nuclear medicine, pathology, physiology, radiology, and surgery met to discuss the current status and future direction of the measurement of extravascular lung water. This report was prepared by the co-organizers and reviewed by the four session chairmen.

Animals↗
PubMed1980

Effect of platelet depletion on lung vascular permeability after microemboli in sheep.

To test whether platelets are necessary for the increased vascular permeability associated with microemboli, we used 16 anesthetized sheep in which we measured lung lymph flow, pulmonary arterial and left atrial pressures, thermodilution cardiac output, and lymph/plasma protein concentration. Injecting glass bead microemboli (200 micrometers diam) until pulmonary vascular resistance increased to three times base-line values caused lung lymph flow to increase at nearly constant lymph-to-plasma protein concentration ratio that is characteristic of increased microvascular permeability. Antiplatelet serum alone caused transient increases in pulmonary vascular resitance and lung lymph flow, but produced no change in steady-state lung fluid balance. After depleting platelets by greater than 97%, tripling pulmonary vascular resistance with emboli resulted in increases in lung lymph and protein flow comparable to that seen in untreated sheep. We injected twice the amount of beads in thrombocytopenic sheep compared to untreated sheep. We conclude that, although platelets do augment the pulmonary hypertension after emboli, they are not essential for the microemboli vascular injury.

Animals↗
PubMed1980

Effect of edema on pulmonary blood flow in the isolated perfused dog lung lobe.

We determined the relationship between the amount of edema and changes in blood flow in the isolated, perfused, and ventilated lower lobe of dog lung. We held vascular pressure constant and measured lobe weight and flow continuously. Vascular pressures were set to produce minimal weight gain in four lobes (controls) and large weight gain in six lobes (edema). In all lobes, the outflow pressure exceeded alveolar pressure at end expiration (zone III conditions). The control lobes gained an average of 20% in weight over 4 h, but blood flow remained constant. They showed interstitial edema histologically and extravascular lung water was increased 38%. The edema lobes gained weight rapidly, ultimately tripling their weight. In these lobes, blood flow remained constant until lobe weight had doubled; then flow decreased progressively to low levels. These lobes showed extensive alveolar edema histologically and extravascular lung water was increased 238%. Pulmonary blood flow is not affected by interstitial edema, but is markedly reduced when alveolar flooding occurs.

Animals↗
PubMed1980

Reflection spectrophotometric measurement of O2 uptake in pulmonary arterioles of cats.

We have attempted to determine both experimentally and theoretically whether a significant quantity of oxygen enters the pulmonary blood before it reaches the alveolar wall capillaries. We built a microspectrophotometer that allowed us to record oxyhemoglobin saturation values with light reflected from transected frozen pulmonary arteries as small as 100 microns in diameter. We prepared anesthetized cats to provide optimal conditions for precapillary oxygenation, quickly froze their lungs with chilled liquid propane, and removed these lungs. We examined lung cross sections with the microspectrophotometer and recorded data indicating the presence of precapillary oxygenation. These data did not tell us how much this process normally contributes to total lung oxygenation because propane did not freeze the lungs fast enough to capture conditions exactly as they are in life. We therefore made several calculations to estimate the extent of precapillary oxygenation using available data on pulmonary arterial geometry and diffusing capacity. We concluded that pulmonary arterial blood may be as much as 15% oxygenated by this process at rest and as much as 100% during oxygen breathing.

Animals↗
PubMed1979

The value of edema fluid protein measurement in patients with pulmonary edema.

Alveolar fluid and plasma proteins were analyzed in 24 patients with florid pulmonary edema, in 21 of whom pulmonary capillary wedge pressure (Pcw) was also measured. In all patients with Pcw less than 20 mm Hg, the edema fluid to plasma protein ratio exceeded 0.6; the mean edema fluid to plasma protein ratio in the four patients with cardiogenic edema (increased Pcw) was 0.46. In the 21 patients in whom full data were available, the net intravascular filtration force (Pcw - plasma colloid osmotic pressure) was less than -4 mm Hg, the value at which (according to others) pulmonary edema should occur, in only 10. When the interstitial colloid osmotic pressure, approximated by the osmotic pressure of edema fluid protein, was added, the net filtration force became positive in 17 of 21 patients. Comparison of the protein concentrations of edema fluid and plasma aids in the diagnostic separation of increased permeability from high hydrostatic pressure edema and adds to our understanding of the relative osmotic and hydrostatic forces that contribute to pulmonary edema when the alveolar-capillary membrane is damaged.

Adolescent↗
PubMed1979

Regional extravascular lung water in normal sheep.

We measured the regional distribution of pulmonary extravascular water to test our prediction that, because of higher vascular hydrostatic pressure in more dependent zones, the bottom of the lung would tend to be wetter than the top. We injected eight normal sheep under halothane anesthesia with 125I-labeled albumin and killed them 5 min later. We suspended the sheep in the prone position and froze them solid in dry ice. We sawed the thorax into horizontal slices, chipped the frozen lung from each, and determined extravascular lung water and hematocrit. Hematocrit was calculated from separately measured red blood cell (tissue hemoglobin) and plasma (125I-albumin) masses. We found regional extravascular water was constant throughout the lung. Regional hematocrit was significantly higher at the lung base than at the apex in these slowly frozen sheep after death. Calculation of extravascular water using a single blood mass marker (hemoglobin) underestimated lung water, more so at the base than at the apex, because blood mass was overestimated. Accurate measurement of blood mass is critical in the calculation of regional lung water.

Albumins↗
PubMed1979

Effect of heparin or fibrinogen depletion on lung fluid balance in sheep after emboli.

Investigators have proposed that fibrinogen, fibrin, or their degradation products are essential for the increased lung vascular permeability to fluid and protein that may occur after microemboli. To test this hypothesis, we used 20 anesthetized ventilated sheep in which we measured lung lymph flow, pulmonary artery and left atrial pressures, thermodilution cardiac output, and lymph/plasma protein concentrations. We injected glass bead microemboli (200 micrometers diam) sufficient to raise pulmonary vascular resistance to three times base-line values and cause increased lung lymph flow with a parallel increase in protein clearance, which is characteristic of increased lung vascular permeability. Neither large doses of heparin (3,000 U/kg) nor fibrinogen depletion with viper venom (ancrod, 2 U/kg), by themselves, affected steady-state pulmonary hemodynamics or lung fluid balance. These treatments prior to giving sufficient amounts of emboli to triple the pulmonary vascular resistance did not prevent the increased lung vascular permeability. We conclude that neither fibrin deposition nor degradation are essential to microembolic lung vascular injury in sheep.

Ancrod↗
PubMed1979

Measurement of pulmonary edema in intact dogs by transthoracic gamma-ray attenuation.

We evaluated the attenuation of the 122 keV gamma ray of cobalt-57 across the thorax of anesthetized dogs as a method for following the time course of lung water changes in acute pulmonary edema induced by either increased microvascular permeability or increased microvascular hydrostatic pressure. The gamma rays traversed the thorax centered on the seventh rib laterally where the lung mass in the beam path was greatest. Calibration measurements in isolated lung lobes demonstrated the high sensitivity and inherent accuracy of the method over a wide range of lung water contents. In control dogs reproducibility averaged +/-3%. Increased permeability edema led to large rapid increases in the transthoracic gamma ray attenuation (TGA), while increased pressure caused an immediate, modest increase in TGA (vascular congestion) followed by a slow further increase over 2 h. There was a fairly good correlation between the increase in extravascular lung water and the change in TGA. The method is simple, safe, and noninvasive and appears to be useful for following the time course of lung water accumulation in generalized lung edema in anesthetized animals.

Animals↗
PubMed1979

Effect of infusing histamine into pulmonary or bronchial artery on sheep pulmonary fluid balance.

We determined the dose-response curve for the effect of histamine on pulmonary fluid and protein exchange when histamine was infused directly into the bronchial artery or pulmonary circulation in anesthetized sheep with a right thoracotomy and an acutely prepared lung lymph fistula. We measured pulmonary hemodynamics, lung lymph flow, and lymph-to-plasma protein concentration ratios in 14 sheep. We infused histamine at constant rates of 0.1, 1, 3, and 10 micrograms/kg . min until a steady state was achieved at each level for 1 h. In the bronchial circulation the lowest effective dose of histamine was 1 microgram/kg . min, which increased lymph flow at constant ratio of lymph to plasma protein concentration. Lymph flow increased further as the dose of infused histamine increased. Infusions into the pulmonary circulation had similar effects, but in addition, pulmonary vascular resistance decreased. The dose-response curves for the effects of histamine on lung lymph and protein flow were identical for the 2 routes of infusion. The effect of histamine was to increase lung microvascular permeability modestly. We conclude that the site of continued action of histamine is probably in the pulmonary microcirculation, because for any given infusion rate, the local concentration of histamine in the bronchial microcirculation must be much greater than that in the pulmonary microcirculation because the ratio of blood flows is so different.

Animals↗