The assessment of the quality of the graft in an animal model for lung transplantation using the metabolomics 1H high-resolution magic angle spinning NMR spectroscopy.

Standards are needed to control the quality of the lungs from nonheart-beating donors as potential grafts. This was here assessed using the metabolomics 1H high-resolution magic angle spinning NMR spectroscopy. Selective perfusion of the porcine bilung block was set up 30 min after cardiac arrest with cold Perfadex®. Lung alterations were analyzed at 3, 6, and 8 h of cold ischemia as compared to baseline and to nonperfused lung. Metabolomics analysis of lung biopsies allowed identification of 35 metabolites. Levels of the majority of the metabolites increased over time at 4°C without perfusion, indicating cellular degradation, whereas levels of glutathione decreased. When lung was perfused at 4°C, levels of the majority of the metabolites remained stable, including levels of glutathione. Levels of uracil by contrast showed a reverse profile, as its signal increased over time in the absence of perfusion while being totally absent in perfused samples. Our results showed glutathione and uracil as potential biomarkers for the quality of the lung. The metabolomics 1H high-resolution magic angle spinning NMR spectroscopy can be efficiently applied for the assessment of the quality of the lung as an original technique characterized by a rapid assessment of intact biopsy samples without extraction and can be implemented in hospital environment.

Severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A prospective French multicenter cohort.

BACKGROUND: A small proportion of patients with chronic obstructive pulmonary disease (COPD) patients present severe pulmonary hypertension (PH), defined by mean pulmonary artery pressure (mPAP) ≥35 mm Hg measured by right heart catheterization. Little is known about the characteristics of severe PH-COPD. The aim of the study based on a national registry was to describe this phenotype. METHODS: We prospectively included and followed patients with incident PH-COPD. Clinical, functional, hemodynamic data at inclusion and follow-up were retrieved. Survival assessed by Kaplan-Meier analysis was the primary end-point. RESULTS: From 2012 to 2016, 99 patients from 13 French centers were included in the study (82 males; median age 66.0 years [interquartile range 62.0-72.0]). At inclusion, most patients had marked dyspnea (55.6% and 22.2% New York Heart Association class III and IV, respectively). During 12 months before inclusion, 42.9% had an exacerbation requiring a hospitalization. Pulmonary function tests showed a moderate obstructive pattern with median (interquartile range) FEV1 50.0 [35.0-63.0] % predicted and low diffusing capacity for carbon monoxide, median 20.0 [16.5-30.6] % predicted. The median values for PaO2 and PaCO2 on room air were 50.0 [44.8-62.0] and 36.0 [31.1-43.0] mm Hg. Median values of mPAP, pulmonary artery occlusion pressure, cardiac index and pulmonary vascular resistance were 42.0 [37.0-48.0] mm Hg, 11.0 [9.0-14.0] mm Hg, 3.0 [2.4-3.6] L/min/m2, and 6.3 [4.2-7.9] WU, respectively. Mean restricted survival was 15.0 [13.9-16.0] months. CONCLUSIONS: Severe PH-COPD is characterized by moderate airway obstruction but marked dyspnea and marked hypoxemia, low DLCO and high mPAP. This phenotype is associated with poor prognosis.

Skeletal and Respiratory Muscle Dysfunctions in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a rare disease, which leads to the progressive loss and remodeling of the pulmonary vessels, right heart failure, and death. Different clinical presentations can be responsible for such a bad prognosis disease and the underlying mechanisms still need to be further examined. Importantly, skeletal and respiratory muscle abnormalities largely contribute to the decreased quality of life and exercise intolerance observed in patients with PAH. At the systemic level, impaired oxygen supply through reduced cardiac output and respiratory muscle dysfunctions, which potentially result in hypoxemia, is associated with altered muscles vascularization, inflammation, enhanced catabolic pathways, and impaired oxygen use through mitochondrial dysfunctions that are likely participate in PAH-related myopathy. Sharing new insights into the pathological mechanisms of PAH might help stimulate specific research areas, improving the treatment and quality of life of PAH patients. Indeed, many of these muscular impairments are reversible, strongly supporting the development of effective preventive and/or therapeutic approaches, including mitochondrial protection and exercise training.

Embolisation of pulmonary arteriovenous malformations using high-frequency jet ventilation: benefits of minimising respiratory motion.

BACKGROUND: To evaluate patient radiation dose and procedural duration recorded during pulmonary arteriovenous malformation (PAVM) embolisation performed using high-frequency jet ventilation (HFJV) as compared with conventional intermittent positive pressure ventilation (IPPV) METHODS: Patients undergoing PAVM embolisation with HFJV assistance after April 2017 were retrospectively identified as group A, and those treated with IPPV before April 2017 as group B. Primary outcomes were patient radiation dose and procedural duration between groups A and B. Secondary outcomes were difference in diaphragmatic excursion between groups A and B, in group A with/without HFJ assistance, technical/clinical success, and complications. RESULTS: Twelve PAVMs were embolised in 5 patients from group A, and 15 PAVMs in 10 patients from group B. Mean patient radiation was significantly lower in group A than in group B (54,307 ± 33,823 mGy cm2 [mean ± standard deviation] versus 100,704 ± 43,930 mGy cm2; p = 0.022). Procedural duration was 33.4 ± 16.1 min in group A versus 57.4 ± 14.9 min in group B (p = 0.062). Diaphragmatic excursion was significantly lower in group A (1.3 ± 0.4 mm) than in group B (19.7 ± 5.2 mm; p < 0.001) and lower with near statistical significance in group A with HFJV than without HFJV (1.3 ± 0.4 mm versus 10.9 ± 3.1 mm; p = 0.062). Technical and clinical success was 100% in both groups, without relevant complications. CONCLUSION: HFJV-assisted PAVM embolisation is a safe, feasible technique resulting in reduced patient radiation doses and procedural time.

Should we perform bilateral-lung or heart­lung transplantation for patients with pulmonary hypertension?

A best evidence topic was constructed according to a structured protocol. The following question was addressed: of the following two procedures, heart­lung transplantation or bilateral-lung transplantation (BLTx), which offers the best outcome for patients with pulmonary hypertension (PH) listed for thoracic transplantation? Of the 77 papers found using a report search for PH and thoracic transplantation, 9 represented the best evidence to answer this clinical question. Overall, 1189 (67%) lung transplantations and 578 (33%) heart­lung transplantations have been reported worldwide for idiopathic PH. For patients with Eisenmenger's syndrome, HLTx represents up to 70% of the transplantation procedures they undergo. On the whole, neither procedure demonstrated an overall survival benefit, when compared with the other. However, PH patients represent a heterogeneous population according to (i) the primary mechanism of PH and (ii) the consequences of PH on right or/and left heart function. With regard to the latter consideration, the current evidence shows that HLTx offers excellent functional and survival outcomes for patients with congenital heart disease and Eisenmenger's syndrome, severe right or/and left heart dysfunction, and who are chronically inotropic dependent. As far as heart dysfunction is concerned, the published evidence approximated cut-off values at 10­25% for the right ventricle ejection fraction (RVEF) and at 32­55% for the left ventricle ejection fraction (LVEF). In the case of lower values for RVEF and LVEF, HLTx should be performed. In all other patients with PH, the evidence demonstrated that BLTx offers a comparable outcome with the advantage of better organ sharing for other recipients. In order to reduce the waiting time on transplantation lists, cardiac repair and BLTx can be offered in experienced centres to patients with simple cardiac anomalies such as atrial septal defect, patent ductus arteriosus or perimembranous ventricular septal defect.