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Biomedical subjects

A D Chanana

Publications and source records attributed to A D Chanana.

At least 19 recordsLinked to original sources
PubMed1989

Effect of PEEP on regional ventilation and perfusion in the mechanically ventilated preterm lamb.

Improvement of gas exchange through closer matching of regional ventilation (V) and lung perfusion (Q) with the application of positive end-expiratory pressure (PEEP) was evaluated in vivo in six mechanically ventilated preterm lambs (107-126 days/145 days gestation). Changes in V and Q were determined from in vivo scintigraphic measurements in four lung regions with inhaled radioactive 81mKr, and infused 81mKr/dextrose and/or [99mTc]MAA as PEEP was applied at 2, 4, and 6 cm H2O in each animal. Dynamic compliance varied between 0.02 and 0.40 ml/cm H2O, which was consistent with surfactant deficiency. As PEEP was increased, the regional distribution of Q shifted from the rostral to the caudal lung regions (p less than 0.02 to less than 0.05), while that of V remained unchanged. Regional V/Q matching improved together with a trend towards improvement of arterial blood gases as PEEP was increased from 2 to 4 cm H2O. Pulmonary scintigraphy offers a noninvasive methodology for the quantitative assessment of regional V and Q matching in preterm lambs and may be clinically applicable to ventilated neonates.

Animals↗
PubMed1987

Distribution of lung-associated lymphocytes from the caudal mediastinal lymph node: effect of antigen.

Lymphocytes from the efferent lymph of the caudal mediastinal lymph node (CMLN) were labelled in vitro with 125I-iododeoxyuridine [125I]UdR and Na2(51)CrO4. The labelled cells were re-infused i.v. and their distribution in organs/tissues was determined 20-24 hr later. As indicated by tissue 125I-activity, pulmonary lymphoblasts had a marked tendency to relocate in the lung, regional pulmonary lymph nodes and spleen. Localization of efferent CMLN lymphoblasts was greater in antigenically stimulated segments compared to unstimulated segments of the lung. Dual antigen experiments indicated that the increased localization was not specific for the antigen which stimulated production of lymphoblasts used for in vitro labelling and reinfusion. Intranodal labelling of blasts by the direct injection of [125I]UdR supported the results obtained from in vitro labelling. In these studies, comparisons were made with the localization of lymphocytes obtained from thoracic duct lymph.

Animals↗
PubMed1986

Fc receptor function on sheep alveolar macrophages.

We have examined the binding to sheep alveolar macrophages (AM) and peripheral blood polymorphonuclear leukocytes (PMN) of sheep immunoglobulin G subclasses or rabbit IgG immune complexes formed between rabbit anti-DNP IgG and DNP-bovine serum albumin. Binding studies using 125I-rabbit IgG immune complexes demonstrated 6.6 +/- 3.5 X 10(4) receptors per alveolar macrophage; these receptors bound immune complexes with an average association constant of 3.3 X 10(7) M-1. Saturation binding was achieved by 90 minutes at 4 degrees C with 6 X 10(-8) M IgG. Binding of subclasses of sheep IgG was examined by immunofluorescence. Only 10% of alveolar macrophages bound monomeric IgG1 and no binding of sheep IgG2 monomer could be demonstrated. In contrast, most peripheral blood PMN (93.0 +/- 9.5%) bound IgG2, but not IgG1. No binding to adult peripheral blood PMN of rabbit IgG immune complexes could be demonstrated. To study further the development of pulmonary host defense, we examined the expression of receptors for IgG immune complexes (Fc gamma R) on alveolar macrophages obtained from animals aged 8 through 180 days. At 8 and 21 days of age, the number of Fc gamma R varied considerably (75,000-192,000 sites per cell) and equalled or even exceeded that of adult sheep. Fc gamma R number declined by 42 and 90 days of age, where a nadir was reached (37,000 +/- 6,000 and 25,000 +/- 6,000 sites, respectively). By 180 days of age, the number of receptors had approached those of normal adult sheep (70,000 +/- 20,000 sites per cell). These studies parallel previous observations that revealed age-related differences in the phagocytic capacity of ovine alveolar macrophages.

Age Factors↗
PubMed1986

Contamination of lung lymph following standard and modified procedures in sheep.

The sheep lung lymph fistula preparation of Staub et al. is reported to be contaminated by systemic lymph. The published estimates of contamination range from 5% (awake sheep) to 60% (anesthetized sheep). In view of these conflicting estimates, we investigated the pre- and postoperative contaminating sources, morphological and functional consequences of the proposed contamination reducing modifications, and base-line lung lymph flow in awake sheep following standard and modified cannulation procedures. Our morphological observations are not compatible with the higher estimates of contamination (25-60%). Evidence of lymph leakage from cauterized lymphatics was found. The lymphatics that appear after diaphragmatic cautery and partial resection of caudal mediastinal lymph node were found to constitute "new" contaminating sources. The lymph flow data from base-line and increased vascular pressure conditions were consistent with the reported low estimates of contamination (5%). We propose simple modifications of the standard procedure of Staub et al. which may be nearly as effective in reducing contamination by extrapulmonary lymph as the more invasive and/or traumatic modifications.

Animals↗
PubMed1986

Postnatal maturation of pulmonary antimicrobial defense mechanisms in conventional and germ-free lambs.

The phagocytic and bactericidal capacities of ovine bronchoalveolar lavage (BAL) cells were investigated as a function of postnatal age. In addition, age-related changes in the elaboration by alveolar macrophages of chemotaxins for neutrophils, concentrations of BAL fluid and serum immunoglobulins, and serum opsonic capacity were determined. BAL cells exhibited major changes in morphology, composition, and in vitro proliferation during the 1st postnatal wk. Studies in germ-free lambs indicated that the antigenic burden of the ambient environment markedly influenced the concentration of BAL neutrophils but had no effect on the influx, phagocytic, and proliferative activities of alveolar macrophages. Phagocytic and bactericidal functions of BAL cells improved rapidly during the 1st postnatal wk, then declined, and did not reattain adult levels until day 180. The capacity of alveolar macrophages to elaborate chemotaxins for neutrophils was deficient at day 8, but not at subsequent ages. The concentration of BAL IgG1 increased until day 8, fell at day 21, and then continued to increase gradually. IgA was not detected in BAL until day 21 and increased rapidly thereafter. Serum opsonic capacity at days 1 and 4 was comparable to that of adult serum, but sera from days 8 to 42 showed a marked reduction in opsonic capacity. Pulmonary antimicrobial defenses in neonatal sheep were thus found to be deficient to some degree throughout the first 3 months of life. It was not until day 180 that the parameters investigated in this study approximated those of adult sheep.

Age Factors↗
PubMed1986

Tracing the leukocyte marker protein in lung fluids and lung-draining lymph nodes during endotoxemia in sheep.

Infusion of Escherichia coli endotoxin into sheep produces a form of acute lung injury that resembles the adult respiratory distress syndrome (ARDS). A large portion of the physiologic derangements produced by E. coli endotoxin in this model is thought to be granulocyte-dependent. We measured the level of L1, a granulocyte and monocyte marker protein, in various tissues and fluids after infusion of E. coli endotoxin into sheep. In an acute study, sheep received saline or 1.25 microgram/kg E. coli endotoxin dissolved in saline, or endotoxin after hydroxyurea-induced granulocytopenia. L1 was measured by radioimmunoassay in efferent lymph from the caudal mediastinal lymph node collected between 5 and 6 h after infusion. In addition, L1 was visualized in both lung-draining and extrapulmonary lymph nodes by indirect immunofluorescence. In a chronic study, sheep were prepared with lung lymph fistulas, and L1 was measured in draining pulmonary lymph, plasma, and bronchoalveolar lavage (BAL) fluid, serially, over a 24-h period after infusion. Mean L1 level in pulmonary lymph in the acute study was 6 times higher by absolute concentration, and 19 times higher when lymph flow rates were taken into account, in the sheep that received endotoxin than in saline-infused sheep or endotoxin-infused, granulocytopenic sheep. Fluorescence was greater in the outer cortical region adjacent to subcapsular, afferent sinuses of lung draining-lymph nodes of endotoxin-treated sheep than in the comparable nodes of saline-infused sheep and endotoxin-infused granulocytopenic sheep. In endotoxin-treated sheep, extrapulmonary lymph nodes were less reactive than lung-draining nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

The status of pulmonary host defense in the neonatal sheep: cellular and humoral aspects.

In consideration of the sheep neonate as a compromised host, we have examined the status of cellular and humoral pulmonary host defense components at selected developmental time points. The dynamic character of the early neonatal LFC population, reflected in changes in subpopulations and proliferative capacity, most probably contributed to the observed changes in in vitro cell function. While certain cell responses, e.g., blood and LFC PMN chemotaxis, appeared intact by day 1, others developed subsequently. The ability of AMs to elaborate a chemotactic factor(s) was first noted at day 21. Bacteria binding and killing presented a biphasic maturation pattern, with full competence not present until day 180. Although the in vitro binding and killing activity of day 8 LFCs was comparable to that of the adult, it may be a poor indicator of in vivo host defense capacity, given the relative paucity of endogenous opsonins at that age. In fact, the interdependence of mediators suggests that the sheep neonate may remain a compromised host during the first 3 months of life. Thereafter, cellular and humoral parameters begin to approximate those of adult sheep and by 180 days of life pulmonary defense, as assessed in this study, is fully developed.

Age Factors↗
PubMed1985

The ovine bronchopulmonary lymph drainage pathways: a model to study pulmonary immune responses.

The lymph drainage pathways of all ovine bronchopulmonary segments (BPS) were traced following intrabronchial instillation of dyes and/or 125IUdR-labeled bacteria. The critical observation, relative to pulmonary immune apparatus, was the identification of at least three BPS-regional lymph node sets with nonoverlapping lymph drainage pathways: right cranial segment-cranial bronchial lymph node; left apical segment-caudal bronchial lymph node; and dorsal-basal, and accessory lobe segments-caudal mediastinal (caudal) lymph node. The efferent lymph drainage pathways from the pulmonary regional lymph nodes were also delineated. This anatomic information is being used to develop a model for studying the respective roles of intrapulmonary, regional, and systemic lymphoid tissues in pulmonary immune responsiveness.

Animals↗
PubMed1984

How alterations in pleural pressure influence esophageal pressure.

Although esophageal pressures have been substituted for direct pleural pressure measurement in humans, we have investigated the validity of this approach under circumstances when left and right pleural pressures are not equal. Esophageal and bilateral pleural pressures in awake sheep were compared by using matched balloon catheters in close proximity. In standing sheep, both end-expiratory pressures and inspiratory pressure swings were similar in all three catheter systems. However, when pleural pressures were made unequal, as during lateral recumbency or unilateral pneumothorax, the esophageal pressure reflected predominantly the right pleural pressure. These results suggest that esophageal pressures are useful estimates of pleural pressure under normal conditions when pleural pressures are equal bilaterally. However, the usefulness of esophageal pressures is limited in the presence of unilateral pneumothorax or other conditions where left and right pleural pressures are unequal. In the lateral decubitus position, positive end-expiratory pleural pressures were consistently observed. This was believed to be due to a combination of contraction of expiratory muscles, rapid respiratory rate resulting in insufficient expiratory time to reach an equilibrium pressure, and increased airways resistance resulting from compression of the dependent lung by the abdominal viscera. A single study in a paralyzed ventilated sheep showed less positive expiratory pressures, which were further reduced to zero or less when the respiratory rate was slowed to 10 breaths/min.

Abdominal Muscles↗
PubMed1984

Acute response to elastase in sheep lungs measured with Ga-67.

The early inflammatory changes in sheep's lungs were studied with Ga-67 citrate, injected i.v. immediately following intrabronchial instillation of different doses of elastase into the right diaphragmatic lobes of 15 sheep. The elastase-induced lesions in the first five sheep (two received 4,000 units; three got 6,000) were imaged up to seven times in an 8-day period to measure the temporal changes in the lesion and to select the appropriate imaging time; the other ten sheep (800-8,000 units) were imaged once at 52 hr. Localization of Ga-67, as seen on the posterior and right lateral projections, was confined to a well-circumscribed region in the right lung field. The lesion could be detected as early as 4 hr after elastase instillation. It decreased to 60% of its initial area at 4 hr, while the total Ga-67 activity in the sheep remained constant after 52-75 hr. Gallium-67 uptake in the lesion correlated positively with the dose of elastase (r = 0.88, p less than 0.001) and with the reduction in perfusion, as determined 4 wk after the elastase instillation (r = 0.66, p less than 0.05). Early Ga-67 uptake in inflammatory lung lesions could therefore be used as a reliable predictor of the size of the acute elastase-induced inflammatory reaction, as well as of the sequelae involving the regional vascular supply 4 wk later.

Animals↗
PubMed1983

Evaluation of the urinary desmosine radioimmunoassay as a monitor of lung injury after endobronchial elastase instillation in sheep.

Thirty male sheep were treated with varying doses of endobronchial elastase. Urinary excretion of elastin peptides was then measured by desmosine radioimmunoassay and compared with pre-enzyme values. Mean linear intercepts were measured in treated and untreated lobes 4 wk later, and in addition, lung perfusion, ventilation, and volume were measured before enzyme treatment and 4 wk later using radionuclide-imaging techniques. Most of the elevation in urinary desmosine excretion occurred in the first 48 h after elastase administration. The increase in desmosine excretion was positively correlated with: enzyme dose (r = 0.74, p less than 0.01), increase in mean linear intercept (r = 0.61, p less than 0.05), decrease in lung perfusion (r = 0.77, p less than 0.01), and decrease in ventilation (r = 0.58, p less than 0.05). These results demonstrate that the urinary desmosine radioimmunoassay is a reliable index of pulmonary elastin breakdown and of several resultant anatomic and physiologic stigmata of pulmonary emphysema.

Amino Acids↗
PubMed1983

Growth of ovine granulocyte-macrophage precursors in vitro without exogenous colony-stimulating activity.

Ovine granulocyte-macrophage colony-forming units (CFU-GM) from peripheral blood and bone marrow were cultured in vitro. The colony-stimulating activity (CSA) was provided by various conditioned-media previously reported to contain CSA and by homologous sheep serum (SS). The maximum number of CFU-GM was observed in the cultures containing SS without the addition of exogenous CSA. The CFU-GM appeared earlier in the cultures containing bone marrow cells when compared to the peripheral blood CFU-GM. Replacement of SS by bovine fetal serum resulted in suboptimal growth of ovine CFU-GM.

Animals↗
PubMed1982

Effects Of NO2 on immune responses in pulmonary lymph of sheep.

Sheep in which the efferent duct of the caudal mediastinal lymph node was cannulated were exposed to 5 ppm No2, 1.5 h/d for 10 or 11 d. Immune responses were assessed by measuring the daily output of hemolytic plaque-forming cells (PFC) in pulmonary lymph, following intrabronchial immunization with horse red blood cells (HRBC) and phytohemagglutinin- (PHA) induced transformation of blood and pulmonary lymph lymphocytes. Sheep immunized 2 d after termination of NO2 exposure had reduced outputs of PFC as compared to those seen in sheep challenged 4 d after NO2 exposure. Animals immunized 4 d after NO2 exposure had outputs similar to those of air control sheep. A reduction of 38-87% in the transformation index of both blood and pulmonary lymph lymphocytes was observed in sheep exposed to NO2. These results suggest that intermittent, short-term exposure to 5 ppm NO2 may temporarily alter pulmonary immune responsiveness.

Animals↗