Adult respiratory distress syndrome: model systems using isolated perfused rabbit lungs.
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Animals↗
Biomedical subjects
D Walmrath
Publications and source records attributed to D Walmrath.
Severe VA/Q mismatch in perfused lungs evoked by sequential challenge with endotoxin and E. coli hemolysin.
Escherichia coli hemolysin (ECH), an important pathogenicity factor in extraintestinal E. coli infections, provokes pulmonary hypertension and microvascular leakage in buffer-perfused rabbit lungs. We investigated gas exchange abnormalities in response to low doses of ECH, lipopolysaccharides (LPS), and sequential and combined application of these bacterial agents by using the multiple inert gas elimination technique. In control lungs and after admixture of 100 ng/ml of LPS, unimodal narrow distribution of perfusion and ventilation to midrange ventilation-perfusion (VA/Q) areas was noted. ECH [0.08 hemolytic units (HU)/ml] caused a moderate increase in pulmonary arterial pressure (< 10 mmHg), progressive lung edema formation (approximately 10 g within 20 min), and a broadening of perfusate and gas flow dispersion. Application of 0.08 HU/ml of ECH in lungs "primed" with 100 ng/ml of LPS in a preceding 125-min perfusion period provoked a large increase in pulmonary arterial pressure (> 50 mmHg within 5 min), rapid edema formation (approximately 10 g within 10 min), and severe VA/Q mismatch with predominance of shunt flow. Vasoconstrictor response and VA/Q mismatch, but not edema formation, were largely inhibited by pretreatment of lungs with acetylsalicylic acid or the thromboxane receptor antagonist BM-13.505. In addition, "rescue" application of BM-13.505 rapidly reversed pressure rise and shunt flow due to sequential LPS and/or ECH stimulation, whereas edema formation was not affected. We conclude that the marked pulmonary hypertension in response to low doses of ECH in LPS-primed lungs is paralleled by severe gas exchange abnormalities with predominance of shunt flow. Both the vasoconstrictor response and the development of shunt are closely related to toxin-induced thromboxane generation.
Animals↗
Aerosolised prostacyclin in adult respiratory distress syndrome.
We studied the effects of aerosolised prostacyclin (PGI2) in three patients with acute severe adult respiratory distress syndrome. 17-50 ng/kg per min, nebulised into the afferent limb of the ventilator circuit, decreased mean pulmonary artery pressure (SEM) from 40.3 (13.5) to 32.0 (3.8) mm Hg (pulmonary vascular resistance fell by 30%); systemic arterial pressure decreased slightly from 76.8 (2.2) to 74.5 (6.1) mm Hg. Concomitantly, the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen increased from 120 (19) to 173 (18), mainly due to redistribution of blood flow from shunt areas to regions of normal ventilation-perfusion. All effects were reversed on drug withdrawal.
Adult↗
A double-blind, randomized, placebo-controlled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile.
Twenty patients hospitalized for acute psoriasis guttata with a minimum 10% of body surface area involvement (range 10-90%) completed a 10-day trial in which they were randomly allocated to receive daily infusions with either an n-3 fatty acid based lipid emulsion [100 ml/day with 2.1 g eicosapentaenoic (EPA) and 21 g docosahexaenoic acid (DHA)] or a conventional n-6 lipid emulsion (EPA + DHA < 0.1 g/100 ml). The severity of disease was evaluated by scoring daily erythema, infiltration, and desquamation and by a subjective scoring of clinical manifestations offered by the patients. Leukotriene (LT) and platelet-activating factor (PAF) generation were investigated in ionophore-stimulated neutrophils obtained on days 0, 1, 3, 5, 10, and 40. Moderate improvement in clinical manifestations was noted in the n-6 group (changes in score systems between 16-25% from baseline within 10 days). In contrast, the severity of disease markedly decreased in all patients of the n-3 group, with improvements in all score systems ranging between 45% and 76% within 10 days (P < 0.05 for each variable). The difference in response to the two regimens was evident within 4-7 days after onset of lipid infusion. A more than ten fold increase in neutrophil EPA-derived 5-lipoxygenase product formation (LTB5, its omega-oxidation products, non-enzymatic degradation products of LTA5 and 5-hydroxyeicosapentaenoic acid) was noted in the n-3 group but not in the n-6 group. Neutrophil PAF generation increased in the n-6 group but decreased in the n-3 group. In conclusion, modulation of eicosanoid metabolism by intravenous n-3 fatty acid supplementation appears to exert a rapid beneficial effect on inflammatory skin lesions in acute guttate psoriasis.
Acute Disease↗
Influence of intravenous n-3 lipid supplementation on fatty acid profiles and lipid mediator generation in a patient with severe ulcerative colitis.
N-3 fatty acids were supplied to a 36-year-old female patient suffering from ulcerative colitis and severe steroid side-effects, in a sequence of parenteral and enteral administration. During a moderately active period of disease, 200 ml d-1 fish oil-derived lipid emulsion (eicosapentaenoic acid [EPA], 4.2 g; docosahexaenoic acid [DHA], 4.2 g) was infused for 9 days, in parallel with rapid tapering of the steroid dose. Disease activity declined rapidly, and the patient was subsequently provided with 16 fish oil capsules per day (EPA, 2.9 g; DHA, 1.9 g) for 2 months. At the end of this period of therapy, severe colitis recurred with intestinal and extraintestinal manifestations. The n-3 lipid emulsion was then used for intravenous alimentation (29 days, maximum dose 300 ml per day); during this time, marked improvement of the inflammatory bowel disease was noted. During both periods of parenteral n-3 lipid administration, total plasma EPA and DHA contents increased several-fold, surpassing that of arachidonic acid; this plasma n-3 fatty acid enrichment was only maintained to a minor extent during the intermediate period of dietary fish oil supplementation. The intravenously administered EPA-containing triglycerides were rapidly hydrolyzed, as evidenced by the appearance of substantial quantities of EPA in the plasma free fatty acid fraction. Platelet and neutrophil total membrane content of EPA and DHA as well as n-3 fatty acid/AA membrane ratios similarly increased during the periods of intravenous n-3 lipid administration and declined during oral fish oil uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Staphylococcal alpha-toxin induced ventilation-perfusion mismatch in isolated blood-free perfused rabbit lungs.
Gas exchange conditions in blood-free perfused isolated rabbit lungs were assessed by the use of the multiple inert gas elimination technique. Under baseline conditions, unimodal narrow distribution of perfusion and ventilation to midrange-ventilation-perfusion (VA/Q) areas was noted. Intravascular challenge with staphylococcal alpha-toxin caused a rapid increase in pulmonary arterial pressure (to > 40 mmHg within approximately 15 min) and delayed-onset (> 10-15 min) lung edema formation, with unaltered ventilation pressures. The vasoconstrictor response was paralleled by a progressive, severe leftward shift of perfusion to areas with low-VA/Q ratios, accompanied by a minor fraction of shunt flow. At pulmonary arterial pressures > 40 mmHg, extreme VA/Q mismatch with near absence of perfusate flow to midrange-VA/Q areas was registered. Vasoconstrictor response and VA/Q mismatch, but not the progressive edema formation, were virtually completely suppressed in lungs pretreated with acetylsalicylic acid or the thromboxane receptor antagonist BM 13505. Moreover, "rescue" application of BM 13505 after onset of alpha-toxin-induced pressor response and gas exchange abnormalities completely reversed pressure elevation and loss of VA/Q matching. We conclude that the marked vasoconstrictor response to staphylococcal alpha-toxin is paralleled by severe VA/Q mismatch with predominant perfusion of low-VA/Q areas independent of lung edema formation. Pressor response and VA/Q mismatch, but not vascular leakage, are suppressed by thromboxane inhibition.
Animals↗
Endotoxin primes perfused rabbit lungs for enhanced vasoconstrictor response to staphylococcal alpha-toxin.
The major pore-forming exotoxin of Staphylococcus aureus, staphylococcal alpha-toxin, causes thromboxane-mediated pulmonary hypertension and prostanoid-independent protracted vascular leakage in perfused rabbit lungs. We asked whether lung responsiveness to the staphylococcal agent would be altered by a preceding period of endotoxin priming. Isolated rabbit lungs were perfused with Krebs-Henseleit buffer in the presence or absence of 100 ng/ml Salmonella abortus equii endotoxin for up to 5 h. The lipopolysaccharide exposure evoked the release of large quantities of tumor necrosis factor into the vascular and alveolar spaces but did not significantly alter pulmonary artery pressure, organ weight, or the repeatedly assessed capillary filtration coefficient (Kfc). Two and 4 h after endotoxin administration, alpha-toxin (10 to 30 ng/ml) was bolus-injected into the pulmonary artery. Toxin-evoked prostanoid generation (TxB2, 6-keto-PGF1 alpha) and pressor responses were markedly accelerated and enhanced in endotoxin-primed lungs, both for the 2 h and the 4 h priming period. No significant influence of endotoxin was noted when applied simultaneously with alpha-toxin. Cyclooxygenase inhibition suppressed the alpha-toxin-evoked pressure rise in both endotoxin-primed and nonprimed lungs. Endotoxin priming did not influence the alpha-toxin-induced protracted increase in Kfc values, assessed in the presence of cyclooxygenase inhibition. We conclude that endotoxin primes rabbit lungs for enhanced prostanoid generation and pulmonary hypertension in response to S. aureus alpha-toxin. Such cooperativity of endotoxin priming and exotoxin triggering may be relevant in critically ill patients suffering from both endotoxemia and gram-positive sepsis.
6-Ketoprostaglandin F1 alpha↗
Differential vasoconstrictor potencies of free fatty acids in the lung vasculature: 2-versus 3-series prostanoid generation.
Pulmonary vasoconstrictor potencies of the 2- and 3-series prostanoid precursors arachidonic acid (AA) and eicosapentaenoic acid (EPA) were compared with each other and three reference fatty acids [palmitic acid (PAL), oleic acid (OA) and eicosatrienoic acid (ETA)]. Dose-effect curves were established from transient pulmonary artery pressor responses (approximately 5-50 mm Hg) evoked by intravascular application of nonesterified fatty acids in buffer-perfused rabbit lungs. Release of di- and trienoic prostanoids into the recirculating perfusate was quantified by a post high-performance liquid chromatography enzyme-linked immunosorbent assay technique. EPA and the three reference fatty acids were used in concentrations up to 10 microM; the rank order of vasoconstrictor potencies was ETA < PAL < OA < EPA. In contrast, AA evoked even larger pressor responses at concentrations two orders of magnitude lower (up to 80 nM). All fatty acids induced both thromboxane A2 and prostaglandin I2 release, ranking with ETA approximately PAL approximately OA < EPA as established for 10 microM concentrations; the dienoic prostanoid release in response to 80 nM AA approximated that elicited by 10 microM EPA. The n-3 fatty acid, however, provoked the liberation of excessive quantities of thromboxane A3 and prostaglandin I3, which surpassed the respective 2-series prostanoids 15- to 20-fold; no 3-series cyclooxygenase products were detected in response to AA, ETA, PAL or OA stimulation. Cyclooxygenase (acetylsalicylic acid) and thromboxane synthetase (OKY 046, Ozagrel, (E)-p-(imidazol-1-ylmethyl)cinnamic acid, C13H12N2O2, MW 228.2) inhibition largely suppressed the EPA-evoked pressor responses.(ABSTRACT TRUNCATED AT 250 WORDS)
8,11,14-Eicosatrienoic Acid↗
[ARDS: possible role of bacterial exotoxin].
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Animals↗
Ventilation-perfusion relationships in isolated blood-free perfused rabbit lungs.
The multiple inert gas elimination technique (MIGET) was applied to blood-free perfused isolated rabbit lungs. Commonly accepted criteria for reliability of the method were found to be fulfilled in this model. Ventilation-perfusion (VA/Q) distributions in isolated control lungs corresponded to those repeatedly detected under physiological conditions. In particular, a narrow unimodal dispersion of perfusate flow was observed: perfusion of low-VA/Q areas ranged below 1% and shunt flow approximately 2-3%; perfusion of high-VA/Q regions was not detected. Gas flow was characterized by narrow dispersion in the midrange-VA/Q areas. Application of a low level of PEEP (1 cmH2O) reduced shunt flow to less than 1%, and low-VA/Q areas were no longer noted. By using this PEEP-level, stable gas exchange conditions were maintained for greater than 5 h of extracorporeal perfusion. Graded embolization with small air bubbles caused a typical rightward shift (to higher VA/Q ratios) of mean ventilation, associated with the appearance of high-VA/Q regions and an increase in dead space ventilation. Mean perfusion was shifted leftward, and shunt flow was approximately doubled. Whole lung lavage with saline for washout of surfactant evoked a progressive manifold increase in shunt flow, accompanied by a moderate rise of perfusate flow to low-VA/Q areas. We conclude that the MIGET can be applied to isolated blood-free perfused rabbit lungs for assessment of gas exchange and that typical patterns of VA/Q mismatch are reproduced in this model.
Animals↗
Type II alveolar epithelial eicosanoid metabolism: predominance of cyclooxygenase pathways and transcellular lipoxygenase metabolism in co-culture with neutrophils.
Arachidonic acid (AA) metabolism was studied in freshly isolated type II alveolar epithelial cells of rabbits. Substantial basal secretion of prostanoids with predominance of prostaglandin (PG) I2 was noted. Challenge with the calcium ionophore A23187 resulted in a time- and dose-dependent increase in the generation of all AA cyclooxygenase products to severalfold values following the rank order of 12-heptadecatrienoic acid (12-HHT) greater than PGI2 greater than PGE2 greater than or equal to thromboxane A2 greater than PGF2 alpha approximately PGD2. Even larger augmentation of prostanoid generation was evoked by challenge with free exogenous AA. Generation of the different AA cyclooxygenase products was inhibited by acetylsalicylic acid with IC50 in the range between 250 and 500 microM. In addition to the prostanoid release, ionophore-challenged type II pneumocytes liberated substantial amounts of AA lipoxygenase products with leukotriene (LT) B4 greater than 15-hydroxyeicosatetraenoic acid (HETE) greater than 12-HETE greater than 5-HETE. Generation of LTs and HETEs was markedly increased upon simultaneous disposal of free exogenous AA. No omega-oxidation of LTB4 was noted, and no evidence for secretion of intact LTA4 was obtained. The epithelial cells displayed avid uptake of exogenously offered LTA4 with subsequent enzymatic conversion to LTB4. Co-stimulation of pneumocytes with neutrophils (PMN) resulted in an amplification of LTB4 generation, paralleled by a decrease in nonenzymatic decay products of PMN-derived LTA4; both phenomena were dose dependent on the pneumocyte-PMN ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Induction of vascular injury by Pseudomonas aeruginosa cytotoxin in rabbit lungs is associated with the generation of different leukotrienes and hydroxyeicosatetraenoic acids.
Pseudomonas aeruginosa cytotoxin, a transmembrane pore-forming protein, causes an increase in pulmonary microvascular permeability with subsequent lung edema formation, possibly related to the induction of arachidonic acid (AA) lipoxygenase products. To investigate this, isolated rabbit lungs were perfused with cytotoxin-containing buffer (6.5 and 13 micrograms of toxin/ml). A severalfold increase in the capillary filtration coefficient was induced, both preceded and accompanied by a marked time- (15-60 min) and dose-dependent release of cysteinyl leukotrienes (LT), LTB4, and 5-, 12-, and 15-hydroxyeicosatetraenoic acids (HETEs) into the lung perfusate. In the bronchoalveolar lavage fluid, corresponding AA-derived products were detected; the total sum of HETEs surpassed that of cysteinyl LTs in this compartment. The lipoxygenase inhibitors AA861 (10 microM) and nordihydroguaiaretic acid (100 microM) and EGTA (5 mM) suppressed the intravascular and alveolar liberation of all 5-lipoxygenase-derived AA metabolites, paralleled by a marked reduction and retardation of microvascular permeability increase (AA861). It thus seems that Pseudomonas cytotoxin induces generation of LTs and HETEs in rabbit lungs that may contribute to the development of pulmonary microvascular injury evoked by this bacterial agent.
Animals↗
Neutrophil passage through isolated perfused rabbit lungs.
Kinetics of polymorphonuclear leukocyte (PMN) lung passage were investigated in ex vivo isolated and ventilated left rabbit lungs, perfused with buffer solution at physiological flow rate. 111In-labeled PMNs of rabbit or human origin were injected into the pulmonary artery, and the first fraction of PMNs that rapidly passed the lung together with coinjected erythrocytes, was collected separately for external radioactivity counting. Washout of initially retained PMNs from the lung was monitored by use of a sodium-iodide detector. Recirculation of cells was avoided by insertion of a filter in the perfusion circuit. A fraction of 16.6 +/- 1.3% of rabbit PMNs rapidly passed the lung vasculature, followed by an exponential washout of initially retained PMNs [half-time (t50) of lung transit 8.1 +/- 0.6 min]. Slightly higher t50 (12.2 +/- 1.0 min) was obtained upon use of human PMNs. Reduction in flow by 50% caused a marked prolongation of PMN transit (t50 = 27.8 +/- 5.1 min), whereas increase in flow to 150% only insignificantly decreased t50. Rise in pulmonary venous pressure to 5 and 8 mmHg caused retardation of PMN lung transit (t50 = 15.3 +/- 0.6 and 31.6 +/- 3.6 min). Preincubation of PMNs with 2 ng/ml endotoxin for 1 h induced marked delay in PMN washout (t50 = 26.1 +/- 2.8 min). In conclusion, single-pass PMN kinetics in isolated lungs correspond to in vivo studies previously reported, thus allowing elucidation of PMN-endothelial interactions in an intact lung vasculature under standardized conditions.
Animals↗
Intravascular anti-IgE challenge in perfused lungs: mediator release and vascular pressor response.
Intravascular application of goat anti-rabbit immunoglobulin E (IgE) was used to stimulate parenchymal mast cells in situ in perfused rabbit lungs. Sustained pulmonary arterial pressure rise was evoked in the absence of lung vascular permeability increase and lung edema formation. Early prostaglandin (PG) D2 and histamine release into the perfusate was documented, accompanied by more sustained liberation of cysteinyl leukotrienes (LT), LTB4, and PGI2. The quantities of these inflammatory mediators displayed the following order: histamine greater than cysteinyl-LT greater than PGI2 greater than LTB4 greater than PGD2. Pressor response and inflammatory mediator release revealed corresponding bell-shaped dose dependencies. Cyclooxygenase inhibition (acetylsalicylic acid) suppressed prostanoid generation, increased LT release, and did not substantially affect pressor response and histamine liberation. BW755 C, a cyclo- and lipoxygenase inhibitor, blocked the release of cysteinyl-LT and markedly reduced the liberation of the other inflammatory mediators as well as the pressor response. The H1-antagonist clemastine caused a moderate reduction of the anti-IgE-provoked pressure rise. We conclude that intravascular anti-IgE challenge in intact lungs provokes the release of an inflammatory mediator profile compatible with in situ lung parenchymal mast cell activation. Pulmonary hypertension represents the predominant vascular response, presumably mediated by cysteinyl-LT and, to a minor extent, histamine liberation.
Animals↗
Human leukoagglutinating antibody evokes cooperative leukotriene synthesis in pulmonary microvasculature. Model of transfusion-related acute lung injury.
Leukoagglutinating antibodies have been implicated in the development of transfusion-related acute lung injury. In the present study, human neutrophil leukotriene generation was provoked by an anti-5b immunoglobulin G, isolated from a multiparous donor plasma that caused noncardiogenic lung edema during transfusion therapy. In 5b-positive polymorphonuclear neutrophils (PMNs), the antibody stimulated marked arachidonic acid metabolism, dependent on the presence of plasma as the complement source. Quantity and profile of lipid mediators (leukotriene B4 and its omega-oxidation products, 5-hydroxyeicosatetraenoic acid, and nonenzymatic hydrolysis products of leukotriene A4) corresponded to those repeatedly described after PMN in vitro stimulation with the artificial calcium ionophore A23187. Anti-5b challenge of PMNs sequestered in the microvasculature of perfused rabbit lungs did, however, induce a markedly modified metabolite profile. Nonenzymatic hydrolysis products of leukotriene A4 were not detected, and 5-hydroxyeicosatetraenoic acid was markedly reduced. In contrast, cysteinyl leukotrienes were measured as predominant compounds, with rapid appearance of leukotriene C4 and more protracted generation of leukotriene E4. Leukotriene B4 and its omega-oxidation products were released with similar kinetics, but in lower amounts, as compared with the isolated PMN stimulation. Anti-5b challenge of PMNs coincubated with pulmonary artery endothelial cells in vitro, but not stimulation of either cell type alone, provoked marked generation of cysteinyl leukotrienes. These findings suggest modulation of PMN 5-lipoxygenase metabolism in favor of leukotriene A4 transfer to adjacent acceptor cells with subsequent enzymatic conversion to cysteinyl leukotrienes under conditions of lung vascular sequestration. Endothelial cells appear to serve as predominant cooperative cells under circumstances of blood-free lung perfusion. PMN-related transcellular eicosanoid synthesis may be involved in the pathogenesis of transfusion-evoked acute lung injury.
Acute Disease↗
Lung vascular injury after administration of viable hemolysin-forming Escherichia coli in isolated rabbit lungs.
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.
6-Ketoprostaglandin F1 alpha↗
Inflammatory lipid mediator generation elicited by viable hemolysin-forming Escherichia coli in lung vasculature.
Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor for E. coli-related extraintestinal infections and sepsis. The possible significance of hemolysin liberation for induction of inflammatory lipid mediators was investigated in isolated rabbit lungs infused with viable bacteria (concentration range, 10(4)-10(7)/ml). Hemolysin-secreting E. coli (E. coli-Hly+), but not an E. coli strain that releases an inactive form of the exotoxin, induced marked lung leukotriene (LT) generation with predominance of cysteinyl LTs. Eicosanoid synthesis was not inhibited in the presence of plasma with toxin-neutralizing capacity. Pre-application of 2 x 10(8) human granulocytes, which sequestered in the lung microvasculature, caused a severalfold increase in leukotriene generation in response to E. coli-Hly+ challenge both in the absence and presence of plasma. Data are presented indicating neutrophil-endothelial cell cooperation in arachidonic acid lipoxygenase metabolism as an underlying mechanism. We conclude that liberation of hemolysin from viable E. coli induces marked lipid mediator generation in lung vasculature, which is potentiated in the presence of neutrophil sequestration and may contribute to microcirculatory disturbances during the course of severe infections.
Animals↗
Reproduction of transfusion-related acute lung injury in an ex vivo lung model.
Leukoagglutinins are implicated in transfusion-related acute lung injury (TRALI). In the present study, severe lung vascular leakage was reproduced by application of a leukoagglutinating antibody of anti-5b specificity in an ex vivo lung model. The antibody originated from a multiparous donor-plasma, observed to cause noncardiogenic edema during transfusion therapy. Heated full plasma (anti-5b-titer 1/128) or purified immunoglobulin G fraction was used for the studies. Ex vivo isolated rabbit lungs were perfused with albumin buffer, and human granulocytes (PMN) were admixed to the recirculating perfusate. In presence of anti-5b antibody plus 5b-positive PMN plus rabbit plasma as complement-source, severe lung edema occurred after a latent period of 3 to 6 hours. Pulmonary artery pressure was only transiently and moderately increased, and the leakage reaction could be traced back to a several-fold increase in lung vascular permeability. In contrast, no vascular leakage was noted in lungs perfused in the absence of anti-5b antibody, PMN, or rabbit plasma. Moreover, no permeability increase occurred on use of 5b-negative PMN. This reproduction of TRALI in an ex vivo lung model corroborates the role of leukoagglutinating antibodies in initiating PMN-dependent respiratory distress and suggests a contribution of concomitant complement activation.
Agglutinins↗