Noncardiogenic Edema Research Articles

Long Non-coding RNA LINC-PINT and LINC00599 Polymorphisms are Associated With High-altitude Pulmonary Edema in Chinese

BackgroundHigh-altitude pulmonary edema (HAPE) is a kind of non-cardiogenic edema with high incidence and life-threatening. This study was designed to explore the association of LINC-PINT and LINC00599 polymorphisms with HAPE susceptibility. MethodsThis study included 244 HAPE patients and 243 age-, sex-matched healthy controls from the Chinese population. The genotypes of polymorphisms were detected using the Agena MassARRAY. The relationship between polymorphisms and HAPE risk was evaluated using a χ2 test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models. ResultsWe observe a significant association between the rs157928 and decreased HAPE risk in genotype model (OR=0.65, 95% CI=0.43–0.98, p=0.038). The subgroup analysis results indicated that rs2272026 was associated with a decreased risk of HAPE in younger patients with age ≤32 (codominant model: p=0.006; recessive model: p=0.005 additive model: p=0.018; and allele model: p=0.012; rs72625676, codominant model: p=0.038; recessive model: p=0.037). Among patients older than 32 years, there was a significantly increased risk of HAPE associated with the rs2272026 and rs1962430 (rs2272026: genotype model: p=0.049; recessive model: p=0.029; rs1962430: genotype model: p=0.024; recessive model: p=0.020). Nevertheless, rs157928 had relationship with significantly reducing the risk of HAPE in the genotype model (p=0.018). ConclusionOur study suggests that LINC-PINT and LINC00599 polymorphisms are associated with HAPE susceptibility in Chinese population.

NR3C1 gene polymorphisms are associated with high-altitude pulmonary edema in Han Chinese

BackgroundHigh-altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic edema which occurs in unacclimatized individuals after rapid ascent to high altitude. NR3C1 gene encodes for glucocorticoid receptor (GR) which plays an important role in stress and inflammation. This study aimed to investigate the association of NR3C1 polymorphisms with the susceptibility to HAPE in Han Chinese.MethodsThe 30 SNPs in the NR3C1 gene were genotyped by the Sequenom MassARRAY SNP assay in 133 HAPE patients (HAPE-p) and 135 matched Han Chinese resistant to HAPE (HAPE-r). The genotypic and allele frequencies, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated, respectively.ResultsThe 12 SNPs showed a significant difference between the HAPE-p and HAPE-r groups. In allelic model analysis, we found that the allele “A” of rs17287745, rs17209237, rs17209251, rs6877893, and rs1866388; the allele “C” of rs6191, rs6188, and rs2918417; the allele “T” of rs33388 and rs4634384; and the allele “G” of rs41423247 and rs10052957 were associated with increased the risk of HAPE. In the genetic model analysis, we found that rs17287745, rs6191, rs6188, rs33388, rs2918417, rs6877893, rs1866388, rs41423247, rs4634384, and rs10052957 were relevant to the increased HAPE risk under the dominant model.In addition, the haplotype AACACTCAAGTG of the 12 SNPs was detected to be significantly associated with HAPE risk (OR = 2.044, 95%CI = 1.339~3.120, P = 0.0008), while the haplotype GGAGCACGACCG was associated with the decreased risk of HAPE (OR = 0.573, 95% CI = 0.333~0.985, P = 0.0422).ConclusionsOur findings provide new evidence for the association between SNPs in NR3C1 and an increased risk of HAPE in the Chinese population. NR3C1 polymorphisms are associated with the susceptibility to HAPE in Han Chinese.

Molecular and Immune Biomarkers in Acute Respiratory Distress Syndrome: A Perspective From Members of the Pulmonary Pathology Society.

Acute respiratory distress syndrome (ARDS) is a multifactorial syndrome with high morbidity and mortality rates, characterized by deficiency in gas exchange and lung mechanics that lead to hypoxemia, dyspnea, and respiratory failure. Histologically, ARDS is characterized by an acute, exudative phase, combining diffuse alveolar damage and noncardiogenic edema, followed by a later fibroproliferative phase. Despite an enhanced understanding of ARDS pathogenesis, the capacity to predict the development of ARDS and to risk-stratify patients with the disease remains limited. Biomarkers may help to identify patients at the greatest risk of developing ARDS, to evaluate response to therapy, to predict outcome, and to improve clinical trials. The ARDS pathogenesis is presented in this article, as well as concepts and information on biomarkers that are currently used clinically or are available for laboratory use by academic and practicing pathologists and the developing and validating of new assays, focusing on the assays' major biologic roles in lung injury and/or repair and to ultimately suggest innovative, therapeutic approaches.

RADIOGRAPHIC APPEARANCE OF PRESUMED NONCARDIOGENIC PULMONARY EDEMA AND CORRELATION WITH THE UNDERLYING CAUSE IN DOGS AND CATS.

Noncardiogenic pulmonary edema is an important cause of respiratory disease in dogs and cats but few reports describe its radiographic appearance. The purpose of this retrospective case series study was to describe radiographic findings in a large cohort of dogs and cats with presumed noncardiogenic pulmonary edema and to test associations among radiographic findings versus cause of edema. Medical records were retrieved for dogs and cats with presumed noncardiogenic edema based on history, radiographic findings, and outcome. Radiographs were reviewed to assess lung pattern and distribution of the edema. Correlation with the cause of noncardiogenic pulmonary edema was evaluated with a Fisher's exact test. A total of 49 dogs and 11 cats were included. Causes for the noncardiogenic edema were airway obstruction (n = 23), direct pulmonary injury (n = 13), severe neurologic stimulation (n = 12), systemic disease (n = 6), near-drowning (n = 3), anaphylaxis (n = 2) and blood transfusion (n = 1). Mixed, symmetric, peripheral, multifocal, bilateral, and dorsal lung patterns were observed in 44 (73.3%), 46 (76.7%), 55 (91.7%), 46 (76.7%), 46 (76.7%), and 34 (57.6%) of 60 animals, respectively. When the distribution was unilateral, pulmonary infiltration involved mainly the right lung lobes (12 of 14, 85.7%). Increased pulmonary opacity was more often asymmetric, unilateral, and dorsal for postobstructive pulmonary edema compared to other types of noncardiogenic pulmonary edema, but no other significant correlations could be identified. In conclusion, noncardiogenic pulmonary edema may present with a quite variable radiographic appearance in dogs and cats.

Sports-related lung injury during breath-hold diving.

The number of people practising recreational breath-hold diving is constantly growing, thereby increasing the need for knowledge of the acute and chronic effects such a sport could have on the health of participants. Breath-hold diving is potentially dangerous, mainly because of associated extreme environmental factors such as increased hydrostatic pressure, hypoxia, hypercapnia, hypothermia and strenuous exercise.In this article we focus on the effects of breath-hold diving on pulmonary function. Respiratory symptoms have been reported in almost 25% of breath-hold divers after repetitive diving sessions. Acutely, repetitive breath-hold diving may result in increased transpulmonary capillary pressure, leading to noncardiogenic oedema and/or alveolar haemorrhage. Furthermore, during a breath-hold dive, the chest and lungs are compressed by the increasing pressure of water. Rapid changes in lung air volume during descent or ascent can result in a lung injury known as pulmonary barotrauma. Factors that may influence individual susceptibility to breath-hold diving-induced lung injury range from underlying pulmonary or cardiac dysfunction to genetic predisposition.According to the available data, breath-holding does not result in chronic lung injury. However, studies of large populations of breath-hold divers are necessary to firmly exclude long-term lung damage.

Bidirectional Crosstalk between Kidney and Lung

Data reported recently suggest that acute kidney injury (AKI) is a systemic disease that adversely affects the function of other organs—including the heart, lung, liver, brain and immune system—which is related to the high mortality rate of affected patients. Kidney and lung function are closely related in both health and disease. Data support deleterious bidirectional crosstalk between the lung and kidney. AKI is a common complication in patients with acute respiratory distress syndrome, and has been reported to exert adverse effects on the lungs. Mortality rates for AKI combined with acute lung injury (ALI) can be up to 80% in critically ill patients. Although AKI-associated ALI presents clinically as increased pulmonary edema, the mechanism of AKI-associated ALI extends beyond simple volume overload. Data from animal studies suggest that AKI-induced pulmonary edema is related to both cardiogenic edema (due to elevated hydrostatic pressure) and non-cardiogenic edema (due to pulmonary endothelial and epithelial cell injury caused by inflammation, oxidative stress, and apoptosis). ALI with mechanical ventilation causes a decline in renal hemodynamic function and apoptosis. Elucidation of the mechanisms of kidney–lung crosstalk would facilitate development of effective therapies and reduce the mortality rate of AKI combined with respiratory failure. Keywords: Acute kidney injury; Respiratory distress syndrome, Adult; Acute lung injury 중심 단어: 급성 ì‹ ë¶€ì „; 급성 호흡곤란증후군; 급성 폐 손상

The Role of Omega-3 Polyunsaturated Fatty Acids in the Treatment of Patients with Acute Respiratory Distress Syndrome: A Clinical Review.

Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process. Recent report on the prognostic value of eicosanoids in patients with ARDS suggests that modulating the inflammatory response through the use of polyunsaturated fatty acids may be a useful strategy for ARDS treatment. The use of enteral diets enriched with eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) has reported promising results, showing an improvement in respiratory variables and haemodynamics. However, the interpretation of the studies is limited by their heterogeneity and methodology and the effect of ω-3 fatty acid-enriched lipid emulsion or enteral diets on patients with ARDS remains unclear. Therefore, the routine use of ω-3 fatty acid-enriched nutrition cannot be recommended and further large, homogeneous, and high-quality clinical trials need to be conducted to clarify the effectiveness of ω-3 polyunsaturated fatty acids.

Abstract T P358: Impact of Clipping Versus Coiling on Postoperative Hemodynamics and Pulmonary Edema after Subarachnoid Hemorrhage

Introduction: Volume management is critical for assessment of vasospasm after aneurysmal subarachnoid hemorrhage (SAH). We compared the impact of surgical clipping versus endovascular coiling on postoperative hemodynamics and pulmonary edema. Methods: This multicenter prospective cohort study measured hemodynamic parameters in patients with SAH using a transpulmonary thermodilution system (PiCCO Plus) from days 1 to 14. Parameters were compared according to treatment strategy. Results: This study included 202 patients, including 160 who underwent clipping and 42 who underwent coiling. There were no differences in global ejection fraction (GEF), cardiac index, systemic vascular resistance index, or global end-diastolic volume index between the clipping and coiling groups in the early period. However, the pulmonary parameters, extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI), were significantly higher in the clipping group during the spasm period. Postoperative C-reactive protein (CRP) level was higher in the clipping group and correlated significantly with postoperative brain natriuretic peptide level. Multivariate analysis found that PVPI and GEF were independently associated with high EVLWI in the early period, suggesting cardiogenic edema (P=0.001 and P=0.004, respectively), and that CRP and PVPI, but not GEF, were independently associated with high EVLWI in the spasm period, suggesting non-cardiogenic edema (P=0.022, P=0.001, and P=0.507, respectively). Conclusions: Postoperative hemodynamics were similar in both groups in the early period, but afterload mismatch may occur in the spasm period. Clipping affects postoperative CRP level and may thereby enhance non-cardiogenic pulmonary edema in the spasm period. Postoperative CRP level may predict pulmonary complications. Trial Registration: University hospital Medical Information Network: UMIN000003794.

Genome Wide Expression Analysis Suggests Perturbation of Vascular Homeostasis during High Altitude Pulmonary Edema

BackgroundHigh altitude pulmonary edema (HAPE) is a life-threatening form of non-cardiogenic edema which occurs in unacclimatized but otherwise normal individuals within two to four days after rapid ascent to altitude beyond 3000 m. The precise pathoetiology and inciting mechanisms regulating HAPE remain unclear.Methodology/Principle findingsWe performed global gene expression profiling in individuals with established HAPE compared to acclimatized individuals. Our data suggests concurrent modulation of multiple pathways which regulate vascular homeostasis and consequently lung fluid dynamics. These pathways included those which regulate vasoconstriction through smooth muscle contraction, cellular actin cytoskeleton rearrangements and endothelial permeability/dysfunction. Some notable genes within these pathways included MYLK; rho family members ARGEF11, ARHGAP24; cell adhesion molecules such as CLDN6, CLDN23, PXN and VCAM1 besides other signaling intermediates. Further, several important regulators of systemic/pulmonary hypertension including ADRA1D, ECE1, and EDNRA were upregulated in HAPE. We also observed significant upregulation of genes involved in paracrine signaling through chemokines and lymphocyte activation pathways during HAPE represented by transcripts of TNF, JAK2, MAP2K2, MAP2K7, MAPK10, PLCB1, ARAF, SOS1, PAK3 and RELA amongst others. Perturbation of such pathways can potentially skew vascular homeostatic equilibrium towards altered vascular permeability. Additionally, differential regulation of hypoxia-sensing, hypoxia-response and OXPHOS pathway genes in individuals with HAPE were also observed.Conclusions/SignificanceOur data reveals specific components of the complex molecular circuitry underlying HAPE. We show concurrent perturbation of multiple pathways regulating vascular homeostasis and suggest multi-genic nature of regulation of HAPE.

The effect of three anaesthetic protocols on the stress response in cane toads (Rhinella marina)

ObjectiveThree anaesthetics (MS222, clove oil and a mixture of ketamine/diazepam) were administered to cane toads to determine their effect on the hypothalamic-pituitary-adrenal (HPA) axis. Time to induction and recovery and any adverse events were also evaluated. Study designProspective randomized experimental trial. AnimalsThirty adult male cane toads (Rhinella marina) with body mass ranging between 130 and 250 g were captured from the field. MethodsThree groups of 10 toads were anaesthetized with ketamine (200 mg kg−1) and diazepam (0.2 mg kg−1) by intramuscular injection, MS222 (3 g L−1) or clove-oil (0.3 mL L−1) both by immersion. Blood samples were collected to determine plasma corticosterone concentrations. Induction and recovery time were recorded in each treatment. After full recovery animals were euthanized and a complete post-mortem examination was performed. ResultsSignificant differences were found in the activation of the HPA axis and in the times of induction and recovery between treatments (p < 0.001). Animals anaesthetized with clove-oil had the highest levels of corticosterone in plasma (42.5 ± 21.6 ng mL−1). No differences were found between ketamine/diazepam (15.0 ± 13.3 ng mL−1) and MS222 (22.0 ± 13.6 ng mL−1) groups. The mean ± SD induction (minutes) and recovery (hours) times respectively were; ketamine/diazepam 66.5 ± 11 and 8 ± 3, clove oil 39 ± 12 and 7.6 ± 3, and MS222 42.5 ± 11 and 1.5 ± 0.5. Clove oil exposure had 30% mortality. Death followed a period of respiratory distress with changes consistent with non-cardiogenic oedema observed at post-mortem examination. Conclusions and Clinical relevanceBased on shorter induction and recovery times and minimal activation of HPA, MS222 is the anaesthetic of choice in cane toads. If it is not possible to use immersion methods of anaesthesia, ketamine/diazepam can be used but induction and recovery times are prolonged. Clove oil had unacceptable mortality in this study and should be used with extreme caution.

Kardiales und nicht kardiales Lungenödem: Pathomechanismen und Ursachen

The development of pulmonary edema is divided in cardiogenic and non-cardiogenic. Cardiogenic edema pathogenically is caused by elevated hydrostatic pressure in the pulmonary capillaries due to left sided congestive heart failure. Non-cardiogenic pulmonary edema is categorized depending on the underlying pathogenesis in low-alveolar pressure, elevated permeability or neurogenic edema. Some important examples of causes are upper airway obstruction like in laryngeal paralysis or strangulation for low alveolar pressure, leptospirosis and ARDS for elevated permeability, and epilepsy, brain trauma and electrocution for neurogenic edema. The differentiation between cardiogenic versus non-cardiogenic genesis is not always straightforward, but most relevant, because treatment markedly differs between the two. Of further importance is the identification of the specific underlying cause in non-cardiogenic edema, not only for therapeutic but particularly for prognostic reasons. Depending on the cause the prognosis ranges from very poor to good chance of complete recovery.

Pulmonary Complications After Acute Kidney Injury

The development of respiratory failure in patients with AKI is a particularly devastating consequence that greatly increases patient mortality. When respiratory failure and AKI occur together, the mortality is greater than 80%. A clear understanding of the mechanisms leading to respiratory failure is of great clinical relevance to patients with AKI in order to prevent and treat this life-threatening complication. Pulmonary edema leading to respiratory failure has been a recognized complication of kidney failure since 1901. Remarkably, the pathogenesis of this complication remains elusive, despite over 100 years of clinical and experimental debate in the literature. A review of this literature suggests that there are 4 causes of pulmonary edema leading to respiratory failure in patients with AKI: (1) volume overload (cardiogenic edema), (2) left ventricular dysfunction (cardiogenic edema), (3) increased lung capillary permeability (noncardiogenic edema), and (4) acute lung injury (noncardiogenic edema with inflammation). In this review, these mechanisms are presented in historical context including the original descriptions of pathology and pathophysiology, recent epidemiologic data, and experimental studies in animals. Although volume overload is a well-accepted mechanism of pulmonary edema in patients with AKI, the purpose of this review was to highlight the evidence showing that noncardiogenic edema and acute lung injury also occur. By recognizing that the pulmonary complications of AKI are not simply from volume overload, specific treatment strategies may be discovered and used to improve outcomes in patients with the ominous and life threatening combination of AKI and respiratory failure.

HLA-Haploidentical Cellular Immunotherapy.

An immune-mediated anti-tumor response is the ultimate goal of allogeneic transplantation for relapsed, refractory malignancies. We developed a transplant protocol with less toxicity compared with standard allogeneic transplantation. We utilize multiple donor lymphocyte infusions after nonmyeloablative HLA-haploidentical stem cell transplantation for refractory disease. We have performed a total of 41 HLA-mismatched transplants with escalation of the CD3+ dose to 2×108 cells/kg using G-CSF primed product, with a conditioning regimen of 100cGy total body irradiation (TBI). Our phase I/II study had 26 with hematologic malignancies. This therapy results in loss of detectable macrochimerism. Despite this, 13 responses, six major, occurred outside of macrochimerism. We have observed a new infusion related clinical entity named haploimmunostorm (HIS), observed after infusion. This syndrome occurred in 26 out of 30 (87%) patients with a CD3+ dose more than 108 cells/kg. In the syndrome, a constellation of symptoms occurred, some with variable penetrance, in which hyperpyrexia and malaise were a constant feature occurring as early as 4 hrs after cell infusion (median of 14 hrs). A morbilliform rash was seen in 40% of patients. Biopsies revealed no evidence of hyperacute or acute GVHD. Diarrhea was present in a 20% of patients; biopsies taken also failed to show any evidence of GVHD. Transient elevations of liver enzymes occurred in 40% of the patients usually. Steroids were used successfully if the HIS syndrome lasted more than 72 hrs. We used a Bioplex machine and analyzed 17-separate cytokine levels serially in these patients beginning with pre-treatment levels. Cytokine level analysis showed a cluster of cytokines that had up to a 1100 fold level increase compared with baseline pretreatment cytokine levels with significant increases of at least 10 fold in IFN-g, IL-10, IL-13, IL-2, IL-5, IL-6, IL-7, IL-8, MCP-1, and MIP-1b. This syndrome appears to be immunologically based and represents neither hyperacute nor acute GVHD. This syndrome is different than an engraftment syndrome reported in some patients undergoing autologous transplant with a different cluster of cytokine elevation (IL-6, IL-8, IL-10, IFN-g, MCP-1, MIP-1b) compared with (IL-1, IL-2, IL-8, TNFa, IFNg) for engraftment syndrome Engraftment syndrome occurs at time of engraftment, opposed to HIS in which may be a rejection syndrome. HIS deviates from engraftment syndrome with absence of noncardiogenic edema, pulmonary infiltrates, renal insufficiency weight gain and encephalopathy. The skin and intestinal biopsy results are distinctly different than GVHD or engraftment syndrome. HIS may be critical to our observed tumor responses. The increased presence of MCP-1 and MIB-1b, which up-regulate NK cell function and recruitment, suggests that NK cells have some role in this syndrome and are possibly mediating tumor response, essentially breaking host tumor tolerance. In summary, we have observed a new clinical entity that was not previously seen and is a result of the donors having a relatively intact immune system at the time of cell infusion. TBI of 100cGy followed by HLA-haploidentical transplant is a biologically active therapy for refractory hematologic disease. The responses outside of chimerism are intriguing and may be related to marrow rejection and or a unique type of cytokine storm. These data further indicate that persistent donor chimerism may not be necessary for durable anti-tumor response. The rejection of donor derived cells, in concert with elevations of specific cytokines, may represent a novel therapeutic approach for hematological malignancies.

The Haploimmunostorm Syndrome: A Distinct Clinical Entity Seen in HLA-Haploidentical Cellular Immunotherapy.

An immune-mediated anti-tumor response is the ultimate goal of allogeneic transplantation for relapsed, refractory malignancies. We developed a transplant protocol with less toxicity compared with standard allogeneic transplantation. We utilize multiple donor lymphocyte infusions after nonmyeloablative HLA-haploidentical stem cell transplantation for refractory disease. We have performed a total of 41 HLA-mismatched transplants with escalation of the CD3+ dose to 2×108 cells/kg using G-CSF primed product, with a conditioning regimen of 100cGy total body irradiation. Our phase I/II study had 26 with hematologic malignancies. This therapy results in loss of detectable macrochimerism. Despite this, 13 responses, six major, occurred outside of macrochimerism. We have observed a new infusion related clinical entity named haploimmunostorm (HIS), observed after infusion. This syndrome occurred in 26 out of 30 (87%) patients with a CD3+ dose more than 1×108 cells/kg. In the syndrome, a constellation of symptoms occurred, some with variable penetrance, in which hyperpyrexia and malaise were a constant feature occurring as early as 4 hrs after cell infusion (median of 14 hrs). A morbilliform rash was seen in 40% of patients. Biopsies revealed no evidence of hyperacute or acute GVHD. Diarrhea was present in a 20% of patients; biopsies taken also failed to show any evidence of GVHD. Transient elevations of liver enzymes occurred in 40% of the patients usually. Steroids were used successfully if the HIS syndrome lasted more than 72 hrs. We used a Bioplex machine and analyzed 17-separate cytokine levels serially in these patients beginning with pre-treatment levels. Cytokine level analysis showed a cluster of cytokines that had up to a 1100 fold level increase compared with baseline pretreatment cytokine levels with significant increases of at least 10 fold in IFN-g, IL-10, IL-13, IL-2, IL-5, IL-6, IL-7, IL-8, MCP-1, and MIP-1b. This syndrome appears to be immunologically based and represents neither hyperacute nor acute GVHD. This syndrome is different than an engraftment syndrome reported in some patients undergoing autologous transplant with a different cluster of cytokine elevation (IL-6, IL-8, IL-10, IFN-g, MCP-1, MIP-1b) compared with (IL-1,IL-2, IL-8, TNFa, IFNg) for engraftment syndrome Engraftment syndrome occurs at time of engraftment, opposed to HIS in which may be a rejection syndrome. HIS deviates from engraftment syndrome with absence of noncardiogenic edema, pulmonary infiltrates, renal insufficiency weight gain and encephalopathy. The skin and intestinal biopsy results are distinctly different than GVHD or engraftment syndrome. The anti-tumor responses may be due to activation of host natural killer and T-cells with increases in MCP-1, MIP-1b and IL-6, essentially breaking host tumor tolerance. In summary, we have observed a new clinical entity that was not previously seen and is a result of the donors having a relatively intact immune system at the time of cell infusion.

Pulmonary oedema after venous air embolism during craniotomy

Pulmonary oedema after venous air embolism during craniotomy

Interactions of lung stretch, hyperoxia, and MIP-2 production in ventilator-induced lung injury.

The use of positive pressure mechanical ventilation can cause ventilator-induced lung injury (VILI). We hypothesized that hyperoxia in combination with large tidal volumes (VT) would accentuate noncardiogenic edema and neutrophil infiltration in VILI and be dependent on stretch-induced macrophage inflammatory protein-2 (MIP-2) production. In rats ventilated with VT 20 ml/kg, there was pulmonary edema formation that was significantly increased by hyperoxia. Total lung neutrophil infiltration and MIP-2 in bronchoalveolar lavage (BAL) fluid were significantly elevated, in animals exposed to high VT both on room air (RA) and with hyperoxia. Hyperoxia markedly augmented the migration of neutrophils into the alveoli. Anti-MIP-2 antibody blocked migration of neutrophils into the alveoli in RA by 51% and with hyperoxia by 65%. We concluded that neutrophil migration into the alveoli was dependent on stretch-induced MIP-2 production. Hyperoxia significantly increased edema formation and neutrophil migration into the alveoli with VT 20 ml/kg, although BAL MIP-2 levels were nearly identical to VT 20 ml/kg with RA, suggesting that other mechanisms may be involved in hyperoxia-augmented neutrophil alveolar content in VILI.

Technique and results of hyperthermic (41°C) isolated lung perfusion with high-doses of cisplatin for the treatment of surgically relapsing or unresectable lung sarcoma metastasis

A technique of hyperthermic isolated lung perfusion (ILP) chemotherapy was developed. Since April 1999, four patients with unilateral (n=2) or bilateral (n=2) sarcoma metastasis confined to a lobe (n=2) or entire lung (n=2) entered into a pilot study of hyperthermic (41 degrees C) ILP with high doses of cisplatin (70 mg/m(2)). Eligibility included drug resistant metastasis and at least four previous surgical metastectomies. The ILP of the lung segments was carried out following metastectomy, for 20-40 min at a rate of 0.3-0.5 l/min, a mean perfusion pressure lower than the own mean pulmonary artery pressure, and an inflow temperature of 41 degrees C or higher. Before and following ILP, the isolated lung segments were flushed with normothermic saline (1 l). Flow was continuously maintained by a centrifugal pump. All patients successfully completed 31.7+/-9 min perfusion time at 41.4+/-0.3 degrees C, and this time-point corresponded to the maximal platinum lung-uptake (93.8 ng/mg tissue). The total vascular isolation was confirmed by continuously low systemic cisplatin plasma levels. There was no systemic drug-related toxicity but all patients experienced transient pulmonary toxicity as non-cardiogenic edema of the treated lung segments. With a median follow-up of 12 months, three patients are alive and disease-free and one died from cerebral metastasis without autopsy evidence of local recurrence 13 months following ILP. Hyperthermic perfusion chemotherapy can be done safely and effectively. It represents a new treatment modality and deserves further investigations for patients with advanced, drug resistant or surgically refractory, lung sarcoma metastasis. However, further studies are needed to limit the ILP-induced pulmonary toxicity.

Noncardiogenic Edema in Marathon Runners

Heatstroke is the most commonly identified cause of collapse following very strenuous exercise. In this case series, investigators identified 7

Estimation of non-cardiogenic pulmonary oedema using dual-frequency electrical impedance.

The study investigates the effects of non-cardiogenic oedema, especially the accumulation of protein in extracellular fluid, on thoracic impedance and proposes a new method of oedema measurement based on an impedance ratio from a dual-frequency measurement. In vitro measurements in a cell containing an albumin-in-saline solution yield a resistance increase when the albumin concentration increases. Subsequently, 13 patients having acute respiratory failure are measured. The single-frequency Z0 measurements and the proposed impedance ratio are compared with extravascular lung water (EVLW) determined by the double indicator dilution method. The single-frequency measurement correlates poorly with EVLW (r = -0.24, p = 0.56). In some patients, a total thoracic impedance increase is found with increasing EVLW. The correlation between the impedance ratio and EVLW is r = -0.79 (p < 0.0005). The ratio decreases as EVLW increases. Thus, when oedema is measured using bio-impedance, cardiogenic and non-cardiogenic oedema yield different results. It is well recognised that cardiogenic oedema decreases total thoracic impedance. In non-cardiogenic oedema, however, protein accumulation causes an impedance increase. The decrease in the impedance ratio as EVLW increases can be explained by the accumulation of albumin in the extracellular compartment.

Acute Lung Failure Induced by Tricyclic Antidepressants

Overdosing of several drugs, such as tricyclic antidepressants, salicylates, and opiates, is known to induce effects like those seen in patients with adult respiratory distress syndrome. By exposing isolated perfused and ventilated rat lungs via the perfusate to six different tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine, mianserine, and maprotiline), we investigated possible effects on ventilation (conductance and dynamic compliance), lung perfusion flow, and edema formation. The effects of these substances were pronounced and appeared within 15 min after exposure. Amitriptyline was studied in greater detail and caused a dose-related (0.01–1.0 mm) reduction in ventilation and perfusion flow. At the highest drug concentration pronounced lung edema was observed. Morphological studies were conducted with a transmission electron microscope. The microscopic preparations showed dose-related edema (amitriptyline 0.1 and 1.0 mm). The effects noted in our experimental studies are similar to those described in patients who have taken an overdose of tricyclic antidepressants. This emphasizes the possibility of a noncardiogenic edema component in these patients.