Exercise and pulsatile pulmonary vascular loading in chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty-five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p < 0.001). ExABN patients had lower PA compliance and higher pulmonary vascular resistance at rest and exercise and prolonged resistance-compliance time product at rest. The physiological relationship between changes in PA pressures relative to PAWP was disrupted in the ExABN group. In CTEPD without PH, exercise RHC revealed latent pulmonary vascular afterload elevations in 58% of patients with more frequent augmentation of pulsatile than resistive pulmonary vascular afterload.

Postoperative but not intraoperative transfusions are associated with respiratory failure after pneumonectomy.

OBJECTIVES: Transfusion of blood products has been associated with increased risk of post-pneumonectomy respiratory failure. It is unclear whether intraoperative or postoperative transfusions confer a higher risk of respiratory failure. Our objective was to assess the role of transfusions in developing post-pneumonectomy respiratory failure. METHODS: We performed a retrospective cohort study using prospectively collected data on consecutive pneumonectomies between 2005 and 2015. Patient records were reviewed for intraoperative/postoperative exposures. Univariable and multivariable analyses were performed. RESULTS: Of the 251 pneumonectomies performed during the study period, 24 (9.6%) patients suffered respiratory failure. Ninety-day mortality was 5.6% (n = 14) and was more likely in patients with respiratory failure (7/24 vs 7/227, P < 0.001). Intraoperative and postoperative transfusions occurred in 42.2% (n = 106) and 44.6% (n = 112) of patients, respectively and were predominantly red blood cells. On univariable analysis, both intraoperative (P = 0.03) and postoperative transfusion (P = 0.004) were associated with a higher risk of respiratory failure. The multivariable model significantly predicted respiratory failure with an area under curve (AUC) = 0.88 (P = 0.001). On multivariable analysis, the only independent predictors of respiratory failure were postoperative transfusions [adjusted odds ratio (aOR) 6.54, 95% confidence interval (CI) 1.74-24.59; P = 0.005] and lower preoperative forced expiratory volume (adjusted OR 0.96, 95% CI 0.93-0.99; P = 0.03). Estimated blood loss was not significantly different (P = 0.91) between those with (median 800 ml, interquartile range 300-2000 ml) and without respiratory failure (median 800 ml, interquartile range 300-2000 ml). CONCLUSIONS: Respiratory failure occurred in 9.6% of patients post-pneumonectomy and confers a higher risk of 90-day mortality. Postoperative (but not intraoperative) transfusion was the strongest independent predictor associated with respiratory failure. Intraoperative transfusion may be in reaction to active/unpredictable blood loss and may not be easily modifiable. However, postoperative transfusion may be modifiable and potentially avoidable. Transfusion thresholds should be assessed in light of potential cost-benefit trade-offs.

Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury.

OBJECTIVES: In vivo lung perfusion (IVLP) is an emergent strategy to treat lung metastases because it allows localized delivery of chemotherapy with minimal systemic exposure. Previously, short-term (± 30 minutes) IVLP resulted in variable efficacy and significant lung toxicity. We hypothesize that a modified IVLP strategy derived from an ex vivo lung perfusion technique could minimize lung injury. Our objective was to demonstrate the feasibility and safety of a modified prolonged (4 hours) IVLP. METHODS: Six Yorkshire pigs were used for the experiments. A thoracotomy was performed, the left pulmonary artery and pulmonary veins were cannulated, and the left lung was isolated in situ. IVLP was performed at normothermia for 4 hours using Steen Solution (XVIVO Perfusion, Göteburg, Sweden) as perfusate. The flow rate was 16% of estimated cardiac output and left atrial pressure was maintained between 3 and 5 mm Hg. Perfusate was deoxygenated and supplied with CO2 to physiologic levels before entering the lungs. A protective mode of ventilation was used. After IVLP, the left lung was allowed to reperfuse for additional 4 hours. Airway dynamics, gas exchange, and pulmonary vascular resistance were used to assess left lung physiology. Histologic signs of lung injury were assessed before and after IVLP, and 4 hours after reperfusion. RESULTS: Lung function parameters were stable throughout the 4-hour IVLP and during reperfusion. No significant histologic evidence of acute lung injury was observed. CONCLUSIONS: Four hours of IVLP is feasible without adding significant lung injury. Prolonged perfusion time and a protective protocol might provide safer and more efficacious treatment of pulmonary metastases.

Initial experience with lung donation after cardiocirculatory death in Canada.

BACKGROUND: Organ donation after cardiac death (DCD) has the potential to alleviate some of the shortage of suitable lungs for transplantation. Only limited data describe outcomes after DCD lung transplantation. This study describes the early and intermediate outcomes after DCD lung transplantation in Canada. METHODS: Data were collected from donors and recipients involved in DCD lung transplantations between June 2006 and December 2008. Described are the lung DCD protocol, donor characteristics, and the occurrence of post-transplant events including primary graft dysfunction (PGD), bronchial complications, acute rejection (AR), bronchiolitis obliterans syndrome (BOS), and survival. RESULTS: Successful multiorgan controlled DCD increased from 4 donors in 2006 to 26 in 2008. Utilization rates of lungs among DCD donors were 0% in 2006, 11% in 2007, and 27% in 2008. The lung transplant team evaluated 13 DCD donors on site, and lungs from 9 donors were ultimately used for 10 recipients. The 30-day mortality was 0%. Severe PGD requiring extracorporeal membrane oxygenation occurred in 1 patient. Median intensive care unit stay was 3.5 days (range, 2-21 days). Hospital stay was 25 days (range, 9-47 days). AR occurred in 2 patients. No early BOS has developed. Nine (90%) patients are alive at a median of 270 days (range, 47-798 days) with good performance status and lung function. One patient died of sepsis 17 months after transplantation. CONCLUSION: DCD has steadily increased in Canada since 2006. The use of controlled DCD lungs for transplantation is associated with very acceptable early and intermediate clinical outcomes.

Screening for malignant pleural mesothelioma and lung cancer in individuals with a history of asbestos exposure.

PURPOSE: We established a screening program for prior asbestos workers using low-dose computed tomography (LDCT). METHODS: Between March 2005 and October 2007 we performed LDCT (50-60 mA, 120 kV, 1.25 mm) in 516 asbestos-exposed individuals. Parenchymal nodules were followed according to lung cancer screening recommendations, morphology and location of pleural plaques was noted in detail. RESULTS: We included 507 men and 9 women (median 60.0 years), 395 (76.6%) were smokers. Annual repeat has been performed in 356 participants. We found plaques in 357 subjects (69.2%), commonly calcified (79.6%), flat (86.6%), and symmetric (86.8%), and mostly involving the costal (96.4%) and diaphragmatic (81.8%) pleura. Uncommon plaques were lobulated (13.2%), right-dominant asymmetric (4.5%), or with effusions (0.1%).We found pulmonary nodules in 371 subjects (71.9%), 91 (17.6%) had at least one nodule > or =5 mm; 10 growing nodules were found on annual repeat LDCT. In 41 individuals, plaques were regarded as atypical; three had new pleural/peritoneal abnormalities on annual repeat LDCT. An interim limited computed tomography of the observed abnormality prompted 10 diagnostic biopsies, resulting in a diagnosis of six lung cancers, two pleural mesothelioma and two peritoneal mesothelioma; overall rate of screen-detected malignancies is 2.1%. There were four interval cancers, diagnosed after baseline (n = 1) or after the annual repeat (n = 3): two pleural and one peritoneal mesothelioma, and one mixed squamous/small cell carcinoma. CONCLUSION: Screening prior asbestos workers detects advanced malignant pleural mesothelioma and early as well as late stage lung cancer. We expect to learn more about the appearance of "early mesothelioma" with continued screening.

Implementation of real-time ultrasound in a thoracic surgery practice.

PURPOSE: The purpose of this study was to implement real-time transthoracic ultrasound in a thoracic surgery and lung transplant practice. DESCRIPTION: Ultrasound units that are light, small, robust, and portable are now available. Obstacles to use include demarcation issues between specialties, training, and a perception that basic ultrasound may be difficult to use. The experience of implementing this is described. EVALUATION: After a training period, 62 studies were performed in 4 months. Patients and clinicians gave positive feedback. The learning time was short, and with ultrasonic guidance, all interventional procedures were successful at the first attempt, without any complications. CONCLUSIONS: Basic transthoracic ultrasound was found to be easy to learn and use by thoracic surgeons, fellows, and specialist nurses. Patients were appreciative. Real-time use may have genuine advantages to patient care.

Ischemia-reperfusion decreases protein tyrosine phosphorylation and p38 mitogen-activated protein kinase phosphorylation in rat lung transplants.

BACKGROUND: Dramatic alterations of protein tyrosine phosphorylation have been found during the ischemia-reperfusion (IR) period of human lung transplantation. IR also induces activation of p38 mitogen-activated protein kinase (p38) in the heart and kidney. The objective of the present study was to determine whether these changes exist in a rat single-lung transplant model for further mechanistic investigations. METHODS: Isogeneic lung transplantation was performed from Lewis (LEW) to LEW rats, whereas allogeneic transplantation was from LEW to Brown Norway (BN) rats. Blood gases and peak airway pressure were monitored. Lung tissues were collected after 6 hours of cold ischemic preservation, after 30 minutes of warm ischemia for lung implantation, and after 2 hours of reperfusion. Protein tyrosine kinase (PTK) and phosphatase (PTP) activities were measured. Protein tyrosine phosphorylation, Src PTK and p38 expression and p38 phosphorylation were examined by western blotting. RESULTS: In both iso- and allografts, the lung function of transplants was very well preserved. Protein tyrosine phosphorylation, PTK and PTP activities were decreased significantly after 2 hours of reperfusion. Src protein level and phosphorylation of p38 were reduced after 2 hours of reperfusion. CONCLUSIONS: During the early IR period of lung transplantation, decreased protein tyrosine phosphorylation may be involved in apoptosis and other biologic changes. The lack of p38 activation suggests that activity of mitogen-activated protein kinase pathways in the lung transplantation setting may be different from other IR processes.