Effect of endotoxin on airway responsiveness to aerosol histamine in sheep

1983 ◽  
Vol 54 (6) ◽  
pp. 1463-1468 ◽  
Author(s):  
A. A. Hutchison ◽  
J. M. Hinson ◽  
K. L. Brigham ◽  
J. R. Snapper
Keyword(s):  
Dynamic Compliance ◽  
Airway Responsiveness ◽  
Lymph Flow ◽  
Lung Mechanics ◽  
Whole Body ◽  
Base Line ◽  
Residual Capacity ◽  
Induced Changes ◽  
Lung Lymph ◽  
Lung Lymph Flow

This study tested the hypothesis that in the awake sheep, airway responsiveness to aerosol histamine would be increased acutely by endotoxemia. Eleven sheep were chronically instrumented to allow for measurements of lung lymph flow, vascular pressures, and lung mechanics. Awake sheep were studied in a whole-body plethysmograph designed to measure dynamic compliance (Cdyn), resistance of the lung (RL), and functional residual capacity (FRC). Pulmonary responsiveness to aerosol histamine was assessed by giving five breaths of increasing concentrations of histamine (0.1–50 mg/ml) until Cdyn decreased to 65% (of control) or until 50 mg/ml of histamine had been given. Escherichia coli endotoxin (0.2–0.5 microgram/kg) was then infused, and at 5 h after endotoxemia pulmonary responsiveness to aerosol histamine was remeasured. After endotoxin, 9 of the 11 sheep exhibited decreased Cdyn at a lower concentration of histamine compared with the preendotoxin level (P less than 0.05). The mean of the log dose of histamine necessary to reduce Cdyn to 65% of control was 1.00 +/- 0.16 (SE) before endotoxin and 0.027 +/- 0.29 5 h after endotoxin; i.e., histamine responsiveness was increased. In the last 3 sheep studied, atropine (0.1 mg/kg iv) was given after the second aerosol histamine challenge, and a third dose-response curve was performed. Atropine did not return the endotoxin-induced increase in histamine responsiveness to base line. There was no correlation between the change in histamine responsiveness and the endotoxin-induced changes in Cdyn, FRC, RL, alveolar-arterial O2 difference, pulmonary arterial pressure, or lung lymph flow.

Evaluation of the mechanism of decreased airway responsiveness in lambs

1989 ◽  
Vol 66 (2) ◽  
pp. 727-731 ◽  
Author(s):  
A. Stecenko ◽  
K. McNicol ◽  
S. Polk
Keyword(s):  
Dynamic Compliance ◽  
Open Lung Biopsy ◽  
Airway Responsiveness ◽  
Lung Mechanics ◽  
Saline Control ◽  
Aerosol Delivery ◽  
Adult Sheep ◽  
Adrenergic Activity ◽  
Residual Capacity

In this study we investigated three possible mechanisms for the decreased airway responsiveness (AR) found in young lambs. To evaluate aerosol delivery, 6 adult sheep (9 mo-3 yr old) and 12 lambs (4–8 wk old) were challenged with aerosol (aH) and intravenous histamine (ivH). Awake animals were intubated and studied in a plethysmograph, which measured dynamic compliance (Cdyn), resistance of the lung, and functional residual capacity. AR to histamine was measured by administration of increasing concentrations of histamine until a significant change in lung mechanics occurred or until the maximum dose of histamine was given. In all six adult sheep, the response to both aH and iVH was a decrease in Cdyn. In two lambs Cdyn was decreased with both aH and ivH, in five lambs with neither, in three lambs with aH only, and in two lambs with ivH only. To examine the role of beta-adrenergic activity in determining AR, six adult sheep and six lambs received ivH and on a separate day ivH with propranolol pretreatment (p + ivH). The median effective dose of histamine that caused a reduction in Cdyn to 65% of normal saline control (ED65Cdyn) for the adult sheep given ivH was 3.60 (range 0.23–4.85) and 0.70 (range 0.49–8.0) micrograms.kg-1.min-1 for p + ivH (P = NS). The median ED65Cdyn for the six lambs was 8.0 micrograms.kg-1.min-1 for both ivH alone and p + ivH. To evaluate the role of airway smooth muscle (SM), AR to aH was quantitated in six adult sheep and six lambs, and then an open-lung biopsy was performed.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of tidal volume and respiratory frequency on lung lymph flow

2005 ◽  
Vol 99 (2) ◽  
pp. 556-563 ◽  
Author(s):  
David B. Pearse ◽  
Robert M. Searcy ◽  
Wayne Mitzner ◽  
Solbert Permutt ◽  
J. T. Sylvester
Keyword(s):  
Tidal Volume ◽  
Lymphatic Vessels ◽  
Lymph Flow ◽  
Edema Formation ◽  
Fluid Filtration ◽  
Induced Changes ◽  
Lung Lymph ◽  
Lung Lymph Flow

Ventilation (V̇) increases lung lymph flow (Q̇l), but the separate effects of tidal volume (Vt) and frequency (f) and the role of V̇-induced changes in edema formation are poorly understood. An isolated, in situ sheep lung preparation was used to examine these effects. In eight sheep with f = 10 min−1, results obtained during 30-min periods with Vt = 5 or 20 ml/kg were compared with values obtained during bracketed 30-min control periods (Vt = 12.5 ml/kg). Eight other sheep with constant Vt (12.5 ml/kg) were studied at f = 5 or 20 min−1 and compared with f = 10 min−1. Three additional groups of six sheep were perfused for 100 min with control V̇ (10 ml/kg, 10 min−1). Vt was then kept constant or changed to 20 or 3 ml/kg during a second 100-min period. Increases in Vt or f increased Q̇l and vice versa, without corresponding effects on the rate of edema formation. For the same change in V̇, changing Vt had a greater effect on Q̇l than changing f. The change in Q̇l caused by an increase in Vt was significantly greater after the accumulation of interstitial edema. The change in Q̇l caused by a sustained increase in Vt was transient and did not correlate with the rate of edema formation, suggesting that V̇ altered Q̇l through direct mechanical effects on edema-filled compartments and lymphatic vessels rather than through V̇-induced changes in fluid filtration.

Permeability of barriers to albumin flux in lungs of sheep resuscitated from hemorrhagic shock

1986 ◽  
Vol 61 (6) ◽  
pp. 2156-2161 ◽  
Author(s):  
A. B. Gorin ◽  
G. Mendiondo
Keyword(s):  
Hemorrhagic Shock ◽  
Extravascular Lung Water ◽  
Weight Ratio ◽  
Equilibrium Concentration ◽  
Dry Weight ◽  
Lymph Flow ◽  
Base Line ◽  
Lung Water ◽  
Lung Lymph ◽  
Lung Lymph Flow

We assessed pulmonary endothelial and epithelial permeability and lung lymph flow in nine adult sheep under base-line conditions and after resuscitation from profound hemorrhagic shock. Animals were mechanically ventilated and maintained on 1% halothane anesthesia while aortic pressure was held at 40 Torr for 3 h. Systemic heparin was not used. After reinfusion of shed blood, sheep recovered from anesthesia and we measured lung lymph flow (QL), lymph-to-plasma concentration ratio for proteins, and time taken to reach half-equilibrium concentration of intravenous tracer albumin in lymph (t1/2). Twenty-four hours after bolus injection of radio-albumin we lavaged subsegments of the right upper lobe and determined fractional equilibration of the tracer in the alveolar luminal-lining layer. In each sheep we had measured these parameters 7 days earlier under base-line conditions. Animals were killed, and the lungs were used for gravimetric determination of extravascular lung water (gravimetric extravascular lung water-to-dry weight ratio) 24 h after resuscitation from shock. Pulmonary endothelial injury after resuscitation was evidenced by marked increase in QL, without fall in lymph-to-plasma ratio. Time taken to reach half-equilibrium concentration fell from 169 +/- 47 (SD) min in base-line studies to 53 +/- 33 min after shock. There was no evidence of lung epithelial injury. Gravimetric extravascular lung water-to-dry weight ratio was significantly increased in these animals killed 24 h after resuscitation (4.94 +/- 0.29) compared with values in our laboratory controls (4.13 +/- 0.09, mean +/- SD). These data demonstrate a loss of lung endothelial integrity in sheep after resuscitation from profound hemorrhagic shock.

Effect of progressive exercise on lung fluid balance in sheep

1988 ◽  
Vol 64 (5) ◽  
pp. 2125-2131 ◽  
Author(s):  
J. H. Newman ◽  
B. J. Butka ◽  
R. E. Parker ◽  
R. J. Roselli
Keyword(s):  
Cardiac Output ◽  
Fluid Balance ◽  
Lymph Flow ◽  
Base Line ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Progressive Exercise ◽  
Pulmonary Arterial ◽  
Lung Lymph ◽  
Lung Lymph Flow

The purpose of this study is to determine the roles of cardiac output and microvascular pressure on changes in lung fluid balance during exercise in awake sheep. We studied seven sheep during progressive treadmill exercise to exhaustion (10% grade), six sheep during prolonged constant-rate exercise for 45–60 min, and five sheep during hypoxia (fraction of inspired O2 = 0.12) and hypoxic exercise. We made continuous measurements of pulmonary arterial, left atrial, and systemic arterial pressures, lung lymph flow, and cardiac output. Exercise more than doubled cardiac output and increased pulmonary arterial pressures from 19.2 +/- 1 to 34.8 +/- 3.5 (SE) cmH2O. Lung lymph flow increased rapidly fivefold during progressive exercise and returned immediately to base-line levels when exercise was stopped. Lymph-to-plasma protein concentration ratios decreased slightly but steadily. Lymph flows correlated closely with changes in cardiac output and with calculated microvascular pressures. The drop in lymph-to-plasma protein ratio during exercise suggests that microvascular pressure rises during exercise, perhaps due to increased pulmonary venous pressure. Lymph flow and protein content were unaffected by hypoxia, and hypoxia did not alter the lymph changes seen during normoxic exercise. Lung lymph flow did not immediately return to base line after prolonged exercise, suggesting hydration of the lung interstitium.

Effects of hypoproteinemia on lung microvascular protein sieving and lung lymph flow

1986 ◽  
Vol 60 (4) ◽  
pp. 1293-1299 ◽  
Author(s):  
R. E. Parker ◽  
N. E. Wickersham ◽  
R. J. Roselli ◽  
T. R. Harris ◽  
K. L. Brigham
Keyword(s):  
Total Protein ◽  
Protein Concentration ◽  
Lymph Flow ◽  
Reflection Coefficients ◽  
Base Line ◽  
Total Protein Concentration ◽  
Total Proteins ◽  
Osmotic Reflection Coefficient ◽  
Lung Lymph ◽  
Lung Lymph Flow

Experiments were conducted on five chronically instrumented unanesthetized sheep to determine the effects of sustained hypoproteinemia on lung fluid balance. Plasma total protein concentration was decreased from a control value of 6.17 +/- 0.019 to 3.97 +/- 0.17 g/dl (mean +/- SE) by acute plasmapheresis and maintained at this level by chronic thoracic lymph duct drainage. We measured pulmonary arterial pressure, left atrial pressure, aortic pressure, central venous pressure, cardiac output, oncotic pressures of both plasma and lung lymph, lung lymph flow rate, and lung lymph-to-plasma ratio of total proteins and six protein fractions for both control base-line conditions and hypoproteinemia base-line conditions. Moreover, we estimated the average osmotic reflection coefficient for total proteins and the solvent drag reflection coefficients for the six protein fractions during hypoproteinemia. Hypoproteinemia caused significant decreases in lung lymph total protein concentration, lung lymph-to-plasma total protein concentration ratio, and oncotic pressures of plasma and lung lymph. There were no significant alterations in the vascular pressures, lung lymph flow rate, cardiac output, or oncotic pressure gradient. The osmotic reflection coefficient for total proteins was found to be 0.900 +/- 0.004 for hypoproteinemia conditions, which is equal to that found in a previous investigation for sheep with a normal plasma protein concentration. Our results suggest that hypoproteinemia does not alter the lung filtration coefficient nor the reflection coefficients for plasma proteins. Possible explanations for the reported increase in the lung filtration coefficient during hypoproteinemia by other investigators are also made.

Effects of increased ventilation on lung lymph flow in unanesthetized sheep

1986 ◽  
Vol 60 (6) ◽  
pp. 2063-2070 ◽  
Author(s):  
S. M. Albelda ◽  
J. H. Hansen-Flaschen ◽  
P. N. Lanken ◽  
A. P. Fishman
Keyword(s):  
Cardiac Output ◽  
Dead Space ◽  
Total Protein ◽  
Minute Ventilation ◽  
Fluid Pressure ◽  
Lymph Flow ◽  
Base Line ◽  
Arterial Blood ◽  
Lung Lymph ◽  
Lung Lymph Flow

To determine the effect of an increase in spontaneous minute ventilation on lung fluid balance, we added external dead space to the breathing circuit of six tracheostomized, unanesthetized, spontaneously breathing sheep in which lung lymph fistulas had been created surgically. The addition of 120–180 ml of dead space caused minute ventilation to increase by 50–100% (secondary to increases in both tidal volume and frequency), without changing pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, or arterial blood gas tensions. The increase in spontaneous ventilation was associated with an average increase of 27% in lung lymph flow (P less than 0.05) and an average reduction of 11% in the lymph-to-plasma concentration ratio (L/P) for total protein (P less than 0.05). Lymph flow and L/P for total protein approached stable values after 2–3 h of hyperpnea, and the increase in lymph flow persisted for at least 18 h of dead-space breathing. Removal of dead space was associated with a rapid return (within 45 min) of lymph flow to base-line levels. These results suggest that hyperpnea increases the pulmonary transvascular filtration rate. Since no changes in vascular pressures or cardiac output were observed, this increase in transvascular filtration is most likely due to a fall in interstitial fluid pressure.

Lung mechanics and airway reactivity in sheep during development of oxygen toxicity

1990 ◽  
Vol 69 (5) ◽  
pp. 1779-1785 ◽  
Author(s):  
M. Fukushima ◽  
L. S. King ◽  
K. H. Kang ◽  
M. Banerjee ◽  
J. H. Newman
Keyword(s):  
Static Pressure ◽  
Positive Airway Pressure ◽  
Oxygen Toxicity ◽  
Dynamic Compliance ◽  
Lung Mechanics ◽  
Lung Edema ◽  
Airway Reactivity ◽  
Residual Capacity ◽  
Lung Lymph ◽  
Airway Abnormalities

The causes of respiratory distress in O2 toxicity are not well understood. The purpose of this study was to better define the airway abnormalities caused by breathing 100% O2. Sheep were instrumented for measurements of dynamic compliance (Cdyn), functional residual capacity by body plethysmography (FRC), hemodynamics, and lung lymph flow. Each day Cdyn and FRC were measured before, during, and after the application of 45 min continuous positive airway pressure (CPAP) at 15 cmH2O. The amount of aerosol histamine necessary to reduce Cdyn 35% from baseline (ED35) was measured each day as was the response to aerosol metaproterenol. Cdyn decreased progressively from 0.083 +/- 0.005 (SE) 1/cmH2O at baseline to 0.032 +/- 0.004 l/cm H2O at 96 h of O2. Surprisingly, FRC did not decrease (1,397 +/- 153 ml at baseline vs. 1,523 +/- 139 ml at 96 h). The ED35 to histamine did not vary among days or from air controls. Metaproterenol produced a variable inconsistent increase in Cdyn. We also measured changes in Cdyn during changes in respiratory rate and static pressure-volume relationships in five other sheep. We found a small but significant frequency dependence of compliance and an increase in lung stiffness with O2 toxicity. We conclude that in adult sheep O2 toxicity reduces Cdyn but does not increase airway reactivity. The large reduction in Cdyn in O2 toxicity results from processes other than increased airway reactivity or reduced lung volume, and Cdyn decreases before the development of lung edema.

Effect of age on lung mechanics and airway reactivity in lambs

1986 ◽  
Vol 61 (6) ◽  
pp. 2074-2080 ◽  
Author(s):  
R. A. Sauder ◽  
K. J. McNicol ◽  
A. A. Stecenko
Keyword(s):  
Citric Acid ◽  
Dynamic Compliance ◽  
Lung Mechanics ◽  
Base Line ◽  
Airway Reactivity ◽  
Airway Opening ◽  
Residual Capacity ◽  
Nasotracheal Tube ◽  
Males And Females ◽  
Significant Change

We studied airway reactivity (AR) to aerosolized histamine, carbachol, and citric acid in lambs 1 mo of age to adulthood. Awake lambs were intubated and studied in a plethysmograph that measured dynamic compliance (Cdyn), resistance of the lung (RL), and functional residual capacity (FRC). Pleural pressure was measured using a Silastic balloon in the pleural space, and airway opening pressure (Pao) was measured using a catheter placed 1–2 cm distal to the nasotracheal tube. At the ages of 1, 3, 5, and 7 mo and adulthood, measurements of Cdyn, RL, and FRC were obtained in 46 sheep (22 males, 24 females). AR to carbachol, histamine, and citric acid was measured in each sheep in randomized order on three separate days by giving increasing concentrations of the drug in a noncumulative fashion. The dose that would have caused a 35% reduction in Cdyn (ED65Cdyn), a doubling of RL (ED200RL), or a 50% increase in FRC (ED150FRC) was calculated. In both males and females, base-line Cdyn increased (r = 0.81, P less than 0.01) with age, as did FRC (r = 0.87, P less than 0.01). There was no significant change in RL in either sex with age or in the group as a whole. There was a significant increase in AR to both histamine and carbachol with increasing age as measured by a decrease in ED65Cdyn (P less than 0.01 and P less than 0.05, respectively) with age. There was no significant change in AR with age as measured by RL or FRC for any of the three bronchoconstrictors tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of inspiratory resistance loading on lung fluid balance in awake sheep

1986 ◽  
Vol 60 (1) ◽  
pp. 198-203 ◽  
Author(s):  
J. E. Loyd ◽  
K. B. Nolop ◽  
R. E. Parker ◽  
R. J. Roselli ◽  
K. L. Brigham
Keyword(s):  
Fluid Balance ◽  
Intrathoracic Pressure ◽  
Lymph Flow ◽  
Base Line ◽  
Plasma Protein Concentration ◽  
Lung Fluid ◽  
Mean Pulmonary Arterial Pressure ◽  
Lung Fluid Balance ◽  
Lung Lymph ◽  
Lung Lymph Flow

Because pulmonary edema has been associated clinically with airway obstruction, we sought to determine whether decreased intrathoracic pressure, created by selective inspiratory obstruction, would affect lung fluid balance. We reasoned that if decreased intrathoracic pressure caused an increase in the transvascular hydrostatic pressure gradient, then lung lymph flow would increase and the lymph-to-plasma protein concentration ratio (L/P) would decrease. We performed experiments in six awake sheep with chronic lung lymph cannulas. After a base-line period, we added an inspiratory load (20 cmH2O) and allowed normal expiration at atmospheric pressure. Inspiratory loading was associated with a 12-cmH2O decrease in mean central airway pressure. Mean left atrial pressure fell 11 cmH2O, and mean pulmonary arterial pressure was unchanged; calculated microvascular pressure decreased 8 cmH2O. The changes that occurred in lung lymph were characteristic of those seen after other causes of increased transvascular hydrostatic gradient, such as increased intravascular pressure. Lung lymph flow increased twice base line, and L/P decreased. We conclude that inspiratory loading is associated with an increase in the pulmonary transvascular hydrostatic gradient, possibly by causing a greater fall in interstitial perimicrovascular pressure than in microvascular pressure.

Relationship between weight gain and lymph flow in dog lungs

1983 ◽  
Vol 245 (1) ◽  
pp. H125-H130 ◽  
Author(s):  
R. E. Drake ◽  
R. L. Scott ◽  
J. C. Gabel
Keyword(s):  
Weight Gain ◽  
Lymph Flow ◽  
Base Line ◽  
Lung Weight ◽  
Lung Fluid ◽  
Lung Fluid Balance ◽  
Extravascular Volume ◽  
Continuous Weight ◽  
Lung Lymph ◽  
Lung Lymph Flow

Lung weight is a useful indicator of increases in lung extravascular volume. In addition, the lung lymph flow rate (QL) is an important factor in lung fluid balance. We have studied the weight and QL responses to elevations in capillary pressure (Pc) in intact dog lung lower left lobes. We measured lobe weight continuously. We also measured QL from small lymph vessels from the same lobes. The base-line QL was 1.7 +/- 1.5 microliter/min, and the weight was constant. After we increased Pc by 8-20 cmH2O, both weight and QL increased transiently. In most lungs the weight reached a new steady state. When we increased Pc further, weight increased continuously; however, QL reached a plateau. The continuous weight gain was due to edema. These results show that weight and QL respond similarly in nonedematous lungs; however, the weight and QL responses in edematous lungs may be different.

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