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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor. In the present study, the possible significance of hemolysin production was investigated in a model of septic lung failure through infusion of viable bacteria in isolated rabbit lungs; 10(4) to 10(7) E. coli/ml perfusate caused a dose- and time-dependent appearance of hemolysin, accompanied by release of potassium, thromboxane A2, and PGI2 into the perfusate. Concomitantly, marked pulmonary hypertension developed. Inhibitor studies suggested that the pressor response was predominantly mediated by pulmonary thromboxane generation. Administration of hemolysin-forming E. coli additionally caused a protracted, dose-dependent increase in the lung capillary filtration coefficient, followed by severe edema formation. The permeability increase was independent of lung prostanoid generation. An E. coli strain that releases an inactive form of hemolysin completely failed to provoke the described biophysical and biochemical responses. Preapplication of 2 x 10(8) human granulocytes was without effect in the present experimental model. We conclude that the hemolysin produced by low numbers of E. coli organisms can provoke thromboxane-mediated pulmonary hypertension and severe vascular leakage. E. coli hemolysin and, possibly, other related cytolysins may thus contribute directly to the pathogenesis of acute respiratory failure under conditions of sepsis or pneumonia.
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PMID:Lung vascular injury after administration of viable hemolysin-forming Escherichia coli in isolated rabbit lungs. 182 93

Three patients underwent single left lung transplantation for end-stage pulmonary fibrosis between June and November 1987. Preoperatively all were housebound, receiving continuous, supplemental oxygen, and their pulmonary function had deteriorated despite corticosteroid and cyclophosphamide therapy. Pulmonary preservation was by means of pulmonary arterial perfusion with modified Euro-Collins solution, 60 ml/kg, at 4 degrees C with adjunctive iloprost (synthetic prostacyclin) infusion. The heart from each donor was used successfully for transplantation. Good early graft function enabled extubation 11, 46, and 96 hours after transplantation. An omental wrap was used around the bronchial anastomosis, and bronchial healing was satisfactory in all. All patients had episodes of pulmonary rejection diagnosed by a combination of symptoms, chest x-ray infiltrates, the exclusion of pneumonitis by bronchoalveolar lavage, and prompt response to "pulse" steroid therapy. Two of the three patients had three episodes of opportunistic pulmonary infections: Herpes simplex pneumonitis, Pneumocystis carinii infection, and Aspergillus pneumonitis. The three patients were discharged from the hospital after 5, 6, and 7 1/2 weeks, respectively. The first and third patients remain alive and well, living essentially normal lives 24 and 19 months after transplantation with no evidence of arterial desaturation on exercise testing while breathing room air. The second patient had symptoms of deteriorating lung function with a progressive decline in forced expiratory volume in 1 second, vital capacity, and diffusion capacity despite repeated "pulse" therapy with combinations of methylprednisolone, antithymocyte globulin, and OKT3 (Ortho Diagnostic Systems Inc., Raritan, N.J.). An open lung biopsy specimen showed obliterative bronchiolitis, and this patient underwent orthotopic lung retransplantation, on the right side. Despite excellent early graft function and early extubation, he died of uncontrolled rejection and general debility after 3 weeks. This early experience in our center with two of three patients surviving 19 to 24 months, respectively, confirms the restoration of good pulmonary function and near normal life-style in patients with end-stage pulmonary fibrosis after single lung transplantation, as first reported by the Toronto Lung Transplant Group. We have used an alternative method of lung preservation (cold crystalloid pulmonary perfusion as opposed to topical cooling, used by the Toronto group), which provided excellent pulmonary preservation up to and beyond 4 hours' storage.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Early results of single lung transplantation in patients with end-stage pulmonary fibrosis. 267 9

We investigated the role of prostacyclin (PGI2) and thromboxane A2 (TxA2), as evidenced by changes in their stable metabolites, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2), in the pathophysiology of acute bacteremic gram-negative pneumonia. Three groups of dogs were inoculated endotracheally: Group I (n = 5) with sterile broth, and Groups II (n = 5) and III (n = 10) with Pseudomonas aeruginosa. Gas exchange, hemodynamics, and plasma prostaglandins were measured before inoculation and hourly thereafter for 5 h in Groups I and II but only once in Group III, 5 h after inoculation. All animals were then killed, and the extent of pneumonia was assessed by lung wet weight and measurement of the percentage of cardiac output (CO) perfusing pneumonic lung using radionuclide-labeled microspheres. None of these measurements changed significantly in Group I, but all dogs in Groups II and III developed severe pneumonia. In Group II, mean arterial oxygen tension fell from 575 +/- 17 to 237 +/- 59 mm Hg (FIO2 = 1.0), with an increase in pulmonary shunt from 6 +/- 2% to 24 +/- 6%. Although TxB2 levels did not change, plasma 6-keto-PGF1 alpha rose progressively as pneumonia developed from baseline levels (less than 100 pg/ml) to a peak level of 890 +/- 114 pg/ml 5 h after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of prostacyclin and thromboxane in the circulatory changes of acute bacteremic Pseudomonas pneumonia in dogs. 327 65

Acute bilateral Pseudomonas aeruginosa pneumonia was induced in 10 anesthetized dogs, after which five dogs received intravenous indomethacin (2 mg/kg) (indomethacin group), whereas five others were infused with saline (2 ml/kg) (control group). Plasma levels of 6-ketoprostaglandin F1 alpha(6-keto-PGF1 alpha) and thromboxane B2 (TxB2), stable metabolites of prostacyclin (PGI2) and thromboxane A2 (TxA2), respectively, were measured by radioimmunoassay. Although TxB2 levels were not different before and after inoculation in either group, 6-keto-PGF1 alpha levels increased from their base-line value in each animal as pneumonia developed (indomethacin group: less than 100 to 330 +/- 90 pg/ml; control group: less than 100 to 630 +/- 300 pg/ml). Both prostaglandins fell to less than 100 pg/ml in each dog after indomethacin infusion, whereas they remained elevated in the control group after infusion of normal saline. Perfusion of consolidated lung regions (Qp/QT), measured with radioactive microspheres and expressed as a percent of total pulmonary blood flow, was dramatically reduced after indomethacin (35 +/- 3 to 16 +/- 1%) with consequent improvement in pulmonary shunt (Qs/QT: 30 +/- 8 to 18 +/- 6%) and arterial O2 tension (PaO2: 123 +/- 25 to 274 +/- 77 Torr). These parameters remained unchanged or deteriorated further in the control group after infusion of saline. Three additional dogs with Pseudomonas pneumonia were studied in which the indomethacin-induced reduction in Qp/QT was substantially but not completely reversed by intravenous infusion of PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of cyclooxygenase blockade on gas exchange and hemodynamics in Pseudomonas pneumonia. 332 11

The effects of Pseudomonas aeruginosa cytotoxin on the pulmonary microvasculature were studied in blood-free, perfused, isolated rabbit lungs. Cytotoxin was administered to the recirculating Krebs Henseleit albumin (1%) buffer during two consecutive 30-min-perfusion phases (phases 1 and 2) at a concentration of 13 micrograms/ml, followed by a third perfusion phase (phase 3) without toxin. After perfusion phases 2 and 3, the capillary filtration coefficient (Kf,c) and vascular compliance were determined gravimetrically from two-step microvascular pressure increments under zero-flow conditions. Cytotoxin caused a continuous release of K+ and lactate dehydrogenase, which started within the first 5 min and amounted to about 50% of the total lung cellular K+ and 5 to 7% of the total lactate dehydrogenase by the end of the experiment. The toxin caused the continuous generation of prostaglandin I2, which was detectable in the perfusates of all perfusion phases at maximum values five times above the control values and which was measured in the bronchoalveolar lavage fluid at the end of the experiment. Thromboxane generation in toxin-treated lungs did not significantly exceed that of control lungs or of lungs with mechanically induced edema. Cytotoxin caused a gradual increase in pulmonary vascular resistance, to maximum values 2.5 times above the control, starting within 1 min; the increase was partially reversible after washout of the toxin. After a lag period of 20 to 30 min, the lungs gained weight, amounting to a mean gain of 9.1 g at the end of the experiments. After perfusion phases 2 and 3, an almost fourfold increase in Kf,c, which was not reversible after washout of the toxin, was measured, whereas the values of vascular compliance were not altered. We conclude that pseudomonal cytotoxin may be an important factor in the pathogenesis of prolonged microvascular injury, encountered in states of P. aeruginosa sepsis or acute lung failure with secondarily acquired P. aeruginosa pneumonia.
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PMID:Pulmonary microvascular injury induced by Pseudomonas aeruginosa cytotoxin in isolated rabbit lungs. 351 62

We compared the effects of high frequency jet ventilation (HFV), conventional ventilation (CMV), and spontaneous breathing (SB) on regional pulmonary blood flows (QLLL), standard cardiopulmonary measurements and the serum levels of the first generation metabolites of prostacyclin (6-keto-PGF1 alpha) and thromboxane A2 (TxB2) in established left lower lobe pseudomonas aeruginosa pneumonia in 11 sheep. Gram negative pneumonia resulted in significant increases in alveolar-arterial oxygen gradients [(A-a)DO2] and pulmonary shunt fractions (Qs/Qt), as well as a significant decrease in QLLL during SB. Significant differences in standard haemodynamics, (A-a)DO2, Qs/Qt, and QLLL were not observed when HFV was compared to CMV. However, serum levels of 6-keto-PGF1 alpha were elevated when the animals underwent HFV. We conclude that HFV is a safe and efficient method of oxygenation and ventilation in unilobar gram negative pneumonia and also results in a significant increase in the serum levels of 6-keto-PGF1 alpha when compared to CMV in sheep. The exact significance of the latter finding is the subject of current investigation.
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PMID:Comparison of regional pulmonary perfusion in lobar pneumonia during high frequency and conventional mechanical ventilation in sheep. 358 95

Pulmonary prostacyclin (PGI2) production, arterial perfusion, and ultrastructure were correlated in rats sacrificed from 1 day to 6 months after a single exposure of 25 Gy of gamma rays to the right hemithorax. PGI2 production by the irradiated lung decreased to approximately half the normal value 1 day after irradiation (P less than 0.05), then increased steadily throughout the study. By 6 months postirradiation, the right lung produced two to three times as much PGI2 as did either shielded left lung or sham-irradiated lungs (P less than 0.05). Perfusion scans revealed hyperemia of the right lung from 1 to 14 days after irradiation. From its peak at 14 days postirradiation, however, perfusion of the irradiated lung decreased steadily, then reached a plateau from 3 to 6 months at less than half that in the shielded left lung. Electron micrographs of the right lung revealed perivascular edema from 1 to 30 days after irradiation. The right lung then exhibited changes typical of radiation pneumonitis followed by progressive interstitial fibrosis. Platelet aggregates were not observed at any time. Thus, decreased PGI2 production is an immediate but transient response of the lung to radiation injury. Then from 2 to 6 months after irradiation, the fibrotic, hypoperfused lung produces increasing amounts of the potent vasodilator and antithrombotic agent, PGI2. Pulmonary PGI2 production and arterial perfusion are inversely correlated for at least 6 months after hemithoracic irradiation.
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PMID:Radiation injury in rat lung. I. Prostacyclin (PGI2) production, arterial perfusion, and ultrastructure. 635 39

In acute hypoxemic respiratory failure of term and near-term neonates, extra- and intrapulmonary right-to-left shunting contribute to refractory hypoxemia. Inhaled nitric oxide (NO) decreases pulmonary arterial pressure and improves ventilation-perfusion mismatch in a variety of animal models and selected human patients. We report on 10 consecutive term and near-term newborns with severe acute hypoxemic respiratory failure due to diaphragmatic hernia, meconium aspiration syndrome, group B streptococcus sepsis, pneumonia or acute respiratory distress syndrome, who received increasing doses of inhaled NO (up to 80 ppm) to improve the arterial partial pressure of oxygen (PaO2). The response to NO and the optimum NO concentration which improved PaO2 varied considerably between patients. Improvement of PaO2 was absent or poor (less than 10 mm Hg) in the 4 newborns with meconium aspiration syndrome and in 1 patient with congenital diaphragmatic hernia, while in the other 5 patients inhaled NO increased the mean (+/- SE) PaO2 from 41 +/- 6 to 57 +/- 9 mm Hg (P < 0.05). Optimum NO concentrations determined by dose-response measurements performed during the first 8 hr of NO inhalation were 8-16 ppm except for 2 newborns with congenital diaphragmatic hernia who required 32 ppm to effectively increase PaO2. Four of the 5 patients in whom the PaO2 rose by more than 10 mm Hg received inhaled NO for extended periods of time (5 to 23 days) with no signs of tachyphylaxis. The optimum NO concentration dropped to less than 3 ppm after prolonged mechanical ventilation or when intravenous prostacyclin was given concomitantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dose-response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: a preliminary report. 756 4

Pseudomonas aeruginosa pneumonia causes a vasculitis of small pulmonary arteries. While the fully developed lesion demonstrates vessel wall necrosis, the early lesion is remarkable for preservation of viable endothelium despite vessel wall invasion by bacteria. Pyocyanin, an exoproduct of P. aeruginosa, markedly inhibited prostacyclin production by pulmonary artery endothelial cells without causing cell lysis. Pyocyanin might after vascular homeostasis in the absence of cytolysis.
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PMID:Pyocyanin from Pseudomonas aeruginosa inhibits prostacyclin release from endothelial cells. 759 Nov 57

Neonatal group B streptococcal (GBS) sepsis and pneumonia cause lung endothelial cell injury. GBS invasion of the lung endothelium may be a mechanism for injury and the release of vasoactive eicosanoids. Pulmonary artery endothelial cells (PAEC) and lung microvascular endothelial cells (LMvEC) were isolated from neonatal piglets and were characterized as endothelial on the basis of morphology, uptake of acyl low-density lipoprotein, factor VIII staining, and formation of tube-like structures on Matrigel. PAEC and LMvEC monolayers were infected with COH-1 (parent GBS strain), isogenic mutants of COH-1 devoid of capsular sialic acid or all capsular polysaccharide, or a noninvasive Escherichia coli strain, DH5 alpha. Intracellular GBS were assayed by plate counting of colony-forming units resistant to incubation with extracellular antibiotics. All GBS strains invaded LMvEC significantly more than PAEC, showing that the site of lung endothelial cell origin influences invasion. DH5 alpha was not invasive in either cell type. Both isogenic mutants invaded PAEC and LMvEC more than COH-1 did, showing that GBS capsular polysaccharide attenuates invasion. Live GBS caused both LMvEC and PAEC injury as assessed by lactate dehydrogenase release; heat-killed GBS and DH5 alpha caused no significant injury. Supernatants from PAEC and LMvEC were assayed by radioimmunoassay for prostaglandin E2 (PGE2), the stable metabolite of prostacyclin (6-keto-PGF1 alpha), and the thromboxane metabolite thromoxane B2. At 4 h, live COH-1 caused no significant increases in eicosanoids from both PAEC and LMvEC. At 16 h, live COH-1, but not heat-killed COH-1, caused a significant increase in 6-keto-PGF1 alpha greater than PGE2 from LMvEC, but not PAEC. We conclude that live GBS injure and invade the lung microvascular endothelium and induce release of prostacyclin and PGE2. We postulate that GBS invasion and injury of the lung microvasculature contribute to the pathogenesis of GBS disease.
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PMID:Group B streptococci (GBS) injure lung endothelium in vitro: GBS invasion and GBS-induced eicosanoid production is greater with microvascular than with pulmonary artery cells. 780 66


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