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Biomedical subjects

R G Spragg

Publications and source records attributed to R G Spragg.

At least 55 records · Page 3Linked to original sources
PubMed1986

Cytoskeletal and morphologic impact of cellular oxidant injury.

The relationship between changes in cell morphology and the cytoskeleton in oxidant injury was examined in the P388D1 cell line. Flow cytometry of cells stained with NBD-phallacidin, a fluorescent probe specific for filamentous (F) actin, revealed a substantial increase in F actin content in H2O2-injured cells over 3-4 hours. Doses of H2O2 as low as 500 microM produced sustained increases in F actin content. Experiments where catalase was used to interrupt H2O2 exposure over a long time course revealed 15-30 minutes to be the critical period of exposure to 5 mM H2O2 necessary for a sustained increase in F actin as well as large increases in membrane blebbing and later cell death. The increase in F actin with H2O2 injury was confirmed with the use of electrophoresis in acrylamide gels of 1% Triton X-100 cytoskeletal extracts from P388D1 cells. Scanning electron microscopy revealed major loss of surface convolutions in addition to the formation of blebs. Fluorescence microscopy of adherent cells using rhodamine phalloidin showed considerable cell rounding and rearrangement of cellular F actin by 30 minutes of exposure to H2O2. Transmission electron microscopy revealed side to side aggregation of F actin bundles (microfilaments) developing during this time. Considerable swelling of mitochondria and other subcellular organelles was seen after 2 hours of injury. The apparent area of attachment to the substrate was markedly diminished in injured cells. H2O2 injury produced a marked increase in F actin with an associated rearrangement of the microfilaments and simultaneous changes in the plasma membrane prior to cell death in the P388D1 cell line.

Actins↗
PubMed1985

Distribution of ventilation in American alligator Alligator mississippiensis.

The regional distribution of ventilation in the multicameral lung of spontaneously ventilating alligators (Alligator mississippiensis) was studied with 133Xe scintigraphy. Frequent gamma camera images of 133Xe washin and washout were obtained and processed to allow evaluation of regional ventilation. Washin of 133Xe to equilibrium occurred in three to four breaths in anterior, central, and posterior compartments. Washin was most rapid in the posterior compartment and slowest in the anterior. The structure of the lungs and distribution of ventilation of inspired gas is consistent with the rapid radial spread of gas through a parallel arrangement of lung units surrounding the central intrapulmonary bronchus. Washout to equilibrium of 133Xe from all compartments occurred within three to four breaths. This rapid washin and washout of gas to all parts of the lung stands in contrast to the lungs of turtles and snakes, in which the caudal air sacs are relatively poorly ventilated.

Alligators and Crocodiles↗
PubMed1985

Mechanisms of interaction between oxygen and granulocytes in hyperoxic lung injury.

Hyperoxia and infused granulocytes act synergistically in producing a nonhydrostatic high-permeability lung edema in the isolated perfused rabbit lung within 4 h, which is substantially greater than that seen with hyperoxia alone. We hypothesized that the interaction between hyperoxia and granulocytes was principally due to a direct effect of hyperoxia on the lung itself. Isolated perfused rabbit lungs that were preexposed to 2 h of hyperoxia (95% O2-5% CO2) prior to the infusion of unstimulated granulocytes (under normoxic conditions) developed significant nonhydrostatic lung edema (P = 0.008) within 2 h when compared with lungs that were preexposed to normoxia (15% O2-5% CO2) prior to granulocyte perfusion. The edema in the hyperoxic-preexposed lungs was accompanied by significant increases in bronchoalveolar lavage (BAL) protein, BAL granulocytes, BAL thromboxane and prostacyclin levels, perfusate chemotactic activity, and lung lipid peroxidation. These findings suggest that the synergistic interaction between hyperoxia and granulocytes in producing acute lung injury involves a primary effect of hyperoxia on the lung itself.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Glutathione cycle activity and pyridine nucleotide levels in oxidant-induced injury of cells.

Exposure of target cells to a bolus of H2O2 induced cell lysis after a latent period of several hours, which was prevented only when the H2O2 was removed within the first 30 min of injury by addition of catalase. This indicated that early metabolic events take place that are important in the fate of the cell exposed to oxidants. In this study, we described two early and independent events of H2O2-induced injury in P388D1 macrophagelike tumor cells: activation of the glutathione cycle and depletion of cellular NAD. Glutathione cycle and hexose monophosphate shunt (HMPS) were activated within seconds after the addition of H2O2. High HMPS activity maintained glutathione that was largely reduced. However, when HMPS activity was inhibited--by glucose depletion or by incubation at 4 degrees C--glutathione remained in the oxidized state. Total pyridine nucleotide levels were diminished when cells were exposed to H2O2, and the breakdown product, nicotinamide, was recovered in the extracellular medium. Intracellular NAD levels fell by 80% within 20 min of exposure of cells to H2O2. The loss of NADP(H) and stimulation of the HMPS could be prevented when the glutathione cycle was inhibited by either blocking glutathione synthesis with buthionine sulfoximine (BSO) or by inhibiting glutathione reductase with (1,3-bis) 2 chlorethyl-1-nitrosourea. The loss of NAD developed independently of glutathione cycle and HMPS activity, as it also occurred in BSO-treated cells.

Animals↗
PubMed1985

Alterations in adenosine triphosphate and energy charge in cultured endothelial and P388D1 cells after oxidant injury.

To investigate mechanisms whereby oxidant injury of cells results in cell dysfunction and death, cultured endothelial cells or P388D1 murine macrophage-like cells were exposed to oxidants including H2O2, O2-. (generated by the enzymatic oxidation of xanthine), or to stimulated polymorphonuclear leukocytes (PMN). Although Trypan Blue exclusion was not diminished before 30 min, cellular ATP was found to fall to less than 30% of control values within 3 min of exposure to 5 mM H2O2. Stimulated PMN plus P388D1 caused a 50% fall in cellular ATP levels. During the first minutes of oxidant injury, total adenylate content of cells fell by 85%. Cellular ADP increased 170%, AMP increased 900%, and an 83% loss of ATP was accompanied by a stoichiometric increase in IMP and inosine. Calculated energy charge [(ATP + 1/2 AMP)/(ATP + ADP + AMP)] fell from 0.95 to 0.66. Exposure of P388D1 to oligomycin plus 2-deoxyglucose (which inhibit oxidative and glycolytic generation of ATP, respectively) resulted in a rate of ATP fall similar to that induced by H2O2. In addition, nucleotide alterations induced by exposure to oligomycin plus 2-deoxyglucose were qualitatively similar to those induced by the oxidant. Loss of cell adenylates could not be explained by arrest of de novo purine synthesis or increased ATP consumption by the Na+-K+ ATPase or the mitochondrial F0-ATPase. These results indicate that H2O2 causes a rapid and profound fall in cellular ATP levels similar to that seen when ATP production is arrested by metabolic inhibitors.

Adenosine Triphosphate↗
PubMed1984

Effect of histamine and propranolol on extravascular lung water.

The ability of an intravenous infusion of 21 micrograms X kg-1 X min-1 histamine diphosphate to cause pulmonary edema was studied in dogs in which beta-blockade either was or was not in effect, since current evidence suggests that beta-blockade can prevent catecholamines from antagonizing the vascular permeability effect of histamine in the systemic circulation. Mixed venous histamine levels ranging from 140 to 580 ng/ml were achieved; norepinephrine and epinephrine levels increased significantly, although in animals receiving propranolol, heart rate remained depressed. Neither lung wet weight-to dry weight ratio nor extravascular lung water increased in animals receiving histamine or histamine and propranolol. We conclude that the inability of histamine to produce substantial pulmonary edema cannot be explained on the basis of catecholamine stimulation of beta-adrenergic receptors within the lung.

Animals↗
PubMed1984

Granulocytes and hyperoxia act synergistically in causing acute lung injury.

Various indirect methods have implicated the polymorphonuclear leukocyte (PMN) as being an important, but not an absolutely necessary, factor in hyperoxia-associated pulmonary edema. By utilizing the cell free isolated perfused rabbit lung model, we demonstrated that the addition of purified, unstimulated granulocytes into the pulmonary artery of hyperoxia exposed lungs resulted in a synergistic edematogenic effect which was statistically significant (p less than 0.05) within only four hours. In addition, significant nonhydrostatic pulmonary edema was produced by both hyperoxia (p less than 0.02) and the addition of PMNs (p = 0.001) when these variables were independently analyzed. These findings help to establish a direct interaction between the role of the PMN and hyperoxia in high permeability lung edema.

Acute Disease↗
PubMed1984

The in vivo behavior of granulocytes labeled with indium-111 in a canine model of pneumococcal pneumonia.

Use of [111In]granulocytes in the study of pulmonary inflammation requires study of their in vivo behavior. To study the pulmonary deposition of these cells and their ability to migrate from the capillary to the alveolus, we injected [111In]granulocytes into dogs 24 h after the induction of a right lower lobe pneumococcal pneumonia. Using external imaging, we found rapid clearance of [111In]granulocytes from the uninvolved lung (with a residual radioactivity of 24.5 +/- 4.2% at 4 h). In contrast, 83 +/- 12.4% of the initial radioactivity was present in inflamed lung at 4 h. Bronchoalveolar lavage fluid from the inflamed lung was more cellular than that from control lung, contained a greater fraction of polymorphonuclear leukocytes (82 +/- 4.1% versus 20 +/- 6.2%), and much greater cell-associated radioactivity (ratio of 423:1, inflamed to control). Autoradiography disclosed that this radioactivity was localized to consolidated alveoli and was not prominently distributed in arterioles or venules or in airways larger than 0.6 mm. We conclude that [111In]granulocytes are biologically active in the setting of acute lung inflammation.

Animals↗
PubMed1983

Angiosarcoma of the lung with fatal pulmonary hemorrhage.

A patient with fatal pulmonary hemorrhage was found to have angiosarcoma of the lung at postmortem examination. This case, occurring in a man with a prior history of industrial exposure in South African copper mines, is the third well-described primary occurrence of this tumor in the lung.

Aged↗
PubMed1983

Use of the balloon-tipped pulmonary artery catheter in pulmonary disease.

Use of the balloon-tipped (Swan-Ganz) pulmonary artery catheter has increased in recent years. The device has three fundamental applications: pressure measurement, flow measurement, and blood sampling. Like any invasive procedure, this catheter should be used only after careful assessment of factors that affect its risk/benefit ratio. There must be a well-defined indication for the procedure. Physicians must be aware of the factors that can influence the validity of the measurements. Familiarity with the technical details of the procedure and with potential complications and how to avoid or manage them is essential to minimize risks and increase the likelihood of obtaining useful information.

Arrhythmias, Cardiac↗
PubMed1983

Chronic thrombotic obstruction of major pulmonary arteries. Results of thromboendarterectomy in 15 patients.

Since 1969, 15 patients, ranging in age from 21 to 67 years, with pulmonary hypertension associated with chronic thrombotic obstruction of major pulmonary arteries have had pulmonary thromboendarterectomy. Symptoms compatible with embolism antedated surgery for periods of 8 months to 18 years; several alternative diagnoses were maintained for months to years. Only 2 of 15 were treated for the initial embolic episode. All patients had dyspnea on exertion and were in New York Heart Association class III-IV before surgery. Resting arterial hypoxemia was common. Resting preoperative mean pulmonary artery pressures ranged from 25 to 66 mm Hg; pulmonary vascular resistances, 420 to 1869 dynes/sec X cm-5. Partial or complete thromboendarterectomy was possible in patients using cardiopulmonary bypass with hypothermia and cardioplegia. All patients showed a fall in pulmonary vascular resistance. All developed some degree of "reperfusion" lung edema and arterial hypoxemia that lasted for a few days to several months. Two patients died during hospitalization. The 13 survivors have been followed for 8 to 144 months (mean, 38.3 months). All patients improved after surgery. One patient died of nonembolic causes; none had recurrent embolism.

Adult↗
PubMed1982

Right and left ventricular response to subcutaneous terbutaline in patients with chronic obstructive pulmonary disease: radionuclide angiographic assessment of cardiac size and function.

To assess the response of the right and left ventricles to the subcutaneous administration of terbutaline sulfate, a beta-2 selective agonist, we evaluated 14 patients with chronic obstructive pulmonary disease (COPD) with equilibrium radionuclide angiography (RNA). Prior to injection, eight patients (57%) had an abnormal right ventricular ejection fraction (RVEF), four (29%) had a low left ventricular ejection fraction (LVEF), and three (21%) had low ejection fractions of both ventricles. After terbutaline injection, RVEF increased in 13 of 14 patients (93%) by 17 +/- 8% (p less than 0.001) while LVEF increased in all patients by 15 +/- 7% (p less than 0.001). Both left and right ventricular end-diastolic volumes decreased (p less than 0.01), while stroke volume was unchanged. Cardiac output rose by 0.8 +/- 1.3 L/min (p less than 0.05), primarily due to the increase in heart rate (10 bpm, p less than 0.001), since stroke volume did not significantly change. We conclude that in patients with COPD subcutaneous terbutaline has significant beta-1 cardiac effects; it increases the heart rate and decreases cardiac size.

Aged↗
PubMed1982

The labeling of rabbit neutrophils with [111In]oxine.

We report here the successful labeling of rabbit peripheral blood neutrophils with [111In]oxine. We found that standard techniques for preparation of rabbit neutrophils, while acceptable for maintenance of in vitro function, rendered the neutrophils ineffective for in vivo use after labeling with 111In. Specifically, rabbit neutrophils were sensitive to the use of hypotonic shock for red cell elimination, centrifugation into a button during preparation, and the presence of oxine during chemotaxis in vitro. Using a carefully modified method of neutrophil preparation and labeling, we found that 111In-labeled rabbit neutrophils retained normal in vitro function, including chemotaxis. In addition, using our method, 34% +/- 5% of labeled neutrophils were recoverable in peripheral blood 5 min after intravenous injection. The half-life of circulating radio-labeled neutrophils was 5.6 +/- 2 h. Continuous external imaging of radio-labeled neutrophils after intravenous injection showed initial lung uptake, followed by rapid clearance of radioactivity in the lungs (50% clearance in 10.5 +/- 3.3 min.) Hepatic radioactivity was maximal by 30 min after injection and thereafter slowly declined. Finally, we found that 111In-labeled rabbit neutrophils migrated to sites of artificially induced inflammation. Our findings indicate that 111In-labeled rabbit neutrophils, if prepared under optimal conditions, should provide a useful tool for investigating the fate of neutrophils in experimental inflammatory conditions in this animal.

Animals↗
PubMed1982

Lung mucociliary transport during high-frequency ventilation.

The effects of high-frequency, low-tidal-volume ventilation (HFV) and conventional intermittent positive-pressure ventilation (IPPV) on lung mucociliary transport were compared in 5 anesthetized, intubated mongrel dogs using a radioactive label. An aerosol of [99mTc]sulfur colloid was delivered to the dogs' airways and the subsequent clearance of isotope was followed over 4 h of either HFV or IPPV. After 4 h of IPPV, approximately 8 to 10% of the initial activity had cleared from the lung. By contrast, practically all the isotope remained in the lung after 4 h of HFV. Although the reasons for this were not definitely established in this study, several other observations were made that relate to this question. First, large amounts of mucus were visible in the trachea immediately after each of the 4-h HFV studies, whereas this was so in only one of the IPPV studies. Second, in 5 of 6 studies, a bolus of radioactive label placed on the posterior trachea after 4 h of HFV was noticed to disperse and move rapidly toward distal airways under the influence of HFV. Third, despite these findings of disturbed mucociliary transport during HFV, measurements of tracheal velocity, using a radioactive bolus technique during conventional ventilation, were the same after 4 h of HFV as after 4 h of IPPV (18.4 +/- 2.6 and 15.0 +/- 1.6 mm/min, respectively). We conclude that in the anesthetized dog HFV may alter mucociliary transport. This is unlikely to be the result of major structural damage to the mucosal surface, because tracheal mucous velocity measured after 4 h of HFV was not different from that after IPPV. It may be partly explained, however, by the retrograde flow of mucus that was observed during HFV in 5 of 6 studies.

Anesthesia, General↗