Taurine attenuates lung ischemia–reperfusion injury after lung transplantation in rats

Purpose

Taurine, the major intracellular free amino acid found in high concentrations in mammalian cells, is known to be an endogenous antioxidant and a membrane-stabilizing agent. It was hypothesized that taurine may be effective in reducing ischemia–reperfusion injury after lung transplantation and an experimental study was conducted in a rat model.

Methods

The number of Sprague–Dawley rats used in the study was 35. Animals were randomized into five groups of 7 rats each, including control, donor I, donor II, ischemia–reperfusion injury, and treatment groups. All animals were exposed to the same experimental conditions in the preoperative period. Rats were fixed in a supine position after the induction. After the rats were shaved, a left pneumonectomy was performed following sternotomy in control, donor I, and donor II groups. The harvested grafts in donor I and donor II groups were transplanted to the rats of the ischemia–reperfusion group and treatment group, respectively. However, taurine was administered intraperitoneally for 3 days before the harvesting procedure in donor II. All harvested lungs were kept in a Euro-Collins solution at +4 °C for 24 h in a half-inflated manner. After harvesting and transplantation, lungs were sampled for histopathological and biochemical analysis.

Results

Malondialdehyde and superoxide dismutase, glutathione peroxidase, and catalase levels were lower in the treatment group than the other groups (p < 0.05). Histopathological findings were better in treatment group than the ischemia–reperfusion group (p < 0.05).

Conclusion

It was demonstrated that donor treatment with taurine resulted in preservation of transplanted lung tissue in respect to histopathological and biochemical findings.     

Registry of the Japanese society of lung and heart–lung transplantation: the official Japanese lung transplantation report 2012

The Japanese Organ Transplant Law was amended, and the revised law took effect in July 2010 to overcome extreme donor shortage and to increase the availability of donor organs from brain-dead donors. It is now possible to procure organs from children. The year 2011 was the first year that it was possible to examine the results of this first extensive revision of the Japanese Organ Transplant Law, which took effect in 1997. Currently, seven transplant centers, including Tohoku, Dokkyo, Kyoto, Osaka, Okayama, Fukuoka and Nagasaki Universities, are authorized to perform lung transplantation in Japan, and by the end of 2011, a total of 239 lung transplants had been performed. The number of transplants per year and the ratio of brain-dead donor transplants increased dramatically after the revision of the Japanese Organ Transplant Law. The survival rates for lung transplant recipients registered with the Japanese Society for Lung and Heart–lung Transplantation were 93.3 % at 1 month, 91.5 % at 3 months, 86.3 % at 1 year, 79.0 % at 3 years, and 73.1 % at 5 years. The survival curves for brain-dead donor and living-donor lung transplantation were similar. The survival outcomes for both brain-dead and living-donor lung transplants were better than those reported by the International Society for Heart and Lung Transplantation. However, donor shortage remains a limitation of lung transplantation in Japan. The lung transplant centers in Japan should continue to make a special effort to save critically ill patients waiting for lung transplantation.     

Moderate hypothermia attenuates lung in flammation inlipopolysaccharide- induced acute lung injury in rats

Objective To investigate the role of moderate h.vpothennia in the lung inflammation of rat acute lung injury induced by lipopolysaccharide(LPS). Methods A rat model of acute lung injury (ALl) was established by in-tin-tracheal instillation of lipopolysaccharide ( 1.5 mg/kg, 0.5 ml) at 16 h after LPS ( 1.0 mg/kg) intraperitoneal adrninis-tmtion. Thirty-four male Sprague Dawley rats were randomly divided into four groups: control group, receiving saline only;LPS group, receiving LPS; hypothennia group, treated with hypothennia without LPS; LPS hypothennia group, treated with LPS and cooled to 32.5℃-33.0℃ as PaO2/FiO2. was below 300 mmHg. Hemodynamics and blood gases were record-ed every hour throughout the study. Rats were killed 4 h after ALl, and lung lavage was performed to measure the tumor ne-crosis factor α(TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) concentrations in bronchoalveolar lavage fluid (BALF) by using enzyme-linked immunosorbent assay (ELISA). Results PaO2/FiO2 was significantly decreased and PaCO2 was increased in the LPS group as compared to their baseline values( P＜0.01). Treatment with hypothermia inhib-ited the increase in PaCO2( P＜0.05) but had no effect on PaO2/FiO2 in the presence of LPS. The administration of LPS significantly increased the concentrations of TNF-α, IL-6 and IL-10 in BALF as compared to the control experiment( P＜0.05, P＜0.01 ). Moderate hypothermia reduced the expressions of TNF-α and IL-6 ( P＜0.01 ) but had no effect on the production of IL-10 ( P＞0.05). Conclusion Moderate hypothermia significantly inhibits proinflammatory cytokine ex-pressions in lipopolysaccharide-induced acute lung injury.     

Lobar lung transplantation—Is it comparable with standard lung transplantation?

Lobar lung transplantation is used mainly for urgent small recipients who are less likely to obtain size matched lungs in due time. Only limited numbers have been published, and we herewith report the largest series of lobar‐LuTX. We analyzed our LuTX database from 1/2001 to 12/2012 and compared the outcome of lobar‐LuTX recipients with those receiving standard LuTX. Seven hundred and seventy‐eighty LuTX (group 1) were performed either in standard technique by implanting the whole lungs (n = 539) or with downsizing by wedge resection of the right middle lobe and/or the left lingula (n = 239). One hundred and thirty‐eight LuTX were performed in lobar technique (group 2) to overcome more pronounced size discrepancies. Patients in group 1 had a different spectrum of diagnoses and were less frequently bridged to LuTX (P < 0.001). Intubation time, ICU stay, and hospital stay were shorter in group 1 (P < 0.001). One‐year survival was 84.8% vs. 65.1%, and 5‐years survival 69.9% vs. 54.9% (P < 0.001). In multivariate analyzes, procedure, diagnosis, and pre‐operative bridging were shown to be significant prognostic factors in survival. Early postoperative outcome in Lobar LuTX was significantly inferior to standard LuTX recipients. However, survival rates of successfully dismissed patients were comparable with standard LuTX (P = 0.168); thereby, Lobar‐LuTX remains an important option in the management of urgent small recipients.     

Can one lung ventilation prevent air embolism in the lung injury victim?

The current literature indicates that patients with hilar lung injury who are receiving positive pressure ventilation are at risk for systemic air embolism, but no studies have yet tested an alternative to the current management: immediate thoracotomy and hilar clamping. We wanted to demonstrate that one lung ventilation of the uninjured lung protects against the formation of arterial air embolism in the presence of contralateral hilar lung injury.In 6 juvenile swine, the right bronchus was selectively ventilated, and ultrasound of the abdominal aorta was used to detect air emboli. The hilum of the left lung was stabbed with a scalpel; after a brief period of monitoring to detect air emboli, the tip of the endotracheal tube was withdrawn into the trachea and the left lung ventilated.Air emboli were detected in 2 animals. The air emboli did not form while the lung was isolated, but they did appear immediately when the endotracheal tube was withdrawn into the trachea. Air was also noted in the chambers of the heart and coronary arteries, and led to fibrillation and death.One lung ventilation appears to protect against arterial air embolism in unilateral hilar lung injury. (Curr Surg 57:349-353)     

γδ T-cell immunotherapy for lung cancer

Lung cancer is the leading cause of cancer death worldwide, yet there are still no satisfactory protocols available for treating this disease, emphasizing the urgency for more effective therapies. Recent clinical trials have provided encouraging evidence of the benefits of certain forms of immunotherapy. Here, we summarize recent developments in the area of γδ T-cell therapy for lung cancer in our center. γδ T cells constitute 2%–10% of T lymphocytes in human blood and play a role in immune surveillance against microbial pathogens and, possibly, cancer. These T cells recognize phosphoantigens via polymorphic γδ T-cell antigen receptors (TCR), as well as the major histocompatibility complex (MHC) class I chain-related molecules, A and B (MICA and MICB), via nonpolymorphic NKG2D receptors in an MHC-unrestricted manner. This implies that γδ T cells could retain antitumor effects despite reduced expression of MHC and tumor antigens on cancer cells. Thus, clinical trials have been conducted to evaluate the safety and efficacy of γδ T-cell-based immunotherapies for non-Hodgkin lymphoma, multiple myeloma, and solid tumors. This review focuses on the current status of γδ T-cell-based immunotherapy for lung cancer.     

How to prevent ventilator-induced lung injury?

The experimental evidence that ventilator could injure lungs through the application of excessive end-inspiratory volumes and transpulmonary pressures has led to major changes in the clinical management of patients suffering from the acute respiratory distress syndrome (ARDS). The prevention of ventilator-induced lung injury has become one of the main goals of current ventilator strategies for patients with ARDS as well as for patients with normal lungs that require mechanical ventilation. Tidal volume reduction allowed for a reduction in mortality that confirmed the clinical relevance of ventilator-induced lung injury. In contrast, strategies for setting positive end-expiratory pressure (PEEP) have been proposed but the optimal PEEP level remains unsettled. Considerable efforts have been made within the last decades to try to develop new ventilator strategies as well as pharmacological and mechanical measures in order to prevent VILI and further improve the outcome of ARDS patients. This review will strive to describe seminal experimental and clinical studies that aimed at preventing the development of VILI.     

Resection of lung metastases--risk or chance?

INTRODUCTION: The resection of pulmonary metastases can extend life of patients, even offering the possibility of cure. A risk analysis of the surgical procedure under the current practice of the thoracic surgery has been performed in this study. MATERIALS AND METHODS: Using a prolective method, data from 199 patients with 300 lung resections for pulmonary metastases done in our university department (1/1994-01/2003) were evaluated. Risk factors and therapy results were investigated in an uni- and multivariate analysis (Fishers Exact Test, Chi-Square and logistic regression). RESULTS: Overall lethality was 1 % and the total morbidity rate was 19 %. The 232 atypical resections were associated with 14 % morbidity rate, while the anatomical and combined ones were associated with 38 % (p = 0.0001). 19 patients revealed a FEV (1) < 1.6 l linked with a morbidity of 42 %. In patients without FEV (1) restriction morbidity was 18 % (p = 0.0172). Both, risk factors and the anatomical resection showed in the multivariate analysis a statistically significant increased morbidity. Additional risk factors (ASA > 2, age over 65, sex or cardial risk factors) did not influence postoperative morbidity. DISCUSSION: According to our data, no patient with good lung function should be withhold from atypical resection of pulmonary metastases offering the possibility of cure with low morbidity. However the indication should be critically evaluated if anatomical resection is required.     

What influences reconvalescence after lung resection?

INTRODUCTION: Reconvalescence after lung resections underlies several influences. The aim of this study was to outline the effect of patient and operative factors. METHODS: Between 1/97 and 6/98 a cross sectional prospective study was undertaken at the University of Ulm. 125 patients with lung resections for various reasons via anterolateral thoracotomy were included. Variants thought to affect postoperative recovery were statistically analysed using uni- and multivariate analysis. A "good postoperative recovery" (GPR) was seen as at least two of the following criteria were fulfilled on the second postoperative day: Spitzer Index >/=6, FEV1 >40% of preoperative measurement, pain on LASA scale 相似文献   

Effects of glucose on rat lung preservation: Report of a study conducted on an isolated lung reperfusion model utilizing another isolated lung as a “deoxygenator”

We describe herein a new experimental model in which an isolated rat lung was ventilated with a mixture of 95% nitrogen and 5% carbon dioxide to decrease the oxygen and increase the carbon dioxide in the perfused blood to create and maintain a gas composition similar to that of venous blood. By utilizing this system as a deoxygenator, pulmonary functions, including gas exchange, could be measured for at least 60 min in isolated and preserved lungs on reperfusion. When the effects of glucose in the flushing and storage solution were examined, 5 mM glucose in the solution resulted in better preservation of the lung, as shown by a higher uptake of oxygen and a lower intratracheal pressure, than when no glucose was given. However, the presence of 50 mM glucose was not beneficial, but rather increased the wet/dry weight ratio of the tissue.     

What is expected in lung function after lung transplantation due to end‐stage pulmonary silicosis?

In this study, we aimed to determine the impact of lung transplantation (LTx) on pulmonary function tests (PFTs) and survival among patients with end‐stage silicosis. We included patients with end‐stage silicosis on the wait list for LTx, between January 1989 and July 2015 (N = 26). Sixteen of these patients received LTx; 10 were eligible, but did not undergo LTx (non‐LTx) during the study period. Retrospective information on PFTs (spirometry [volumes and flows], 6‐minute walking test [6MWT], and DLCO) was retrieved from patients’ medical charts, including baseline information for all patients and follow‐up information for the LTx. At baseline, most patients presented with spirometric and 6MWT values that were suggestive of severe disease (FEV₁/FVC 76.5 ± 29.7; 6MWT 267.4 ± 104.5 m). Significant increases in these values were observed at follow‐up in the LTx (P = .036 and .151, respectively). The overall median survival of patients in the LTx and non‐LTx was 3.35 years (95% CI: 0.16‐14.38) and 0.78 years (95% confidence interval [CI]: 0.12‐3.65) (P = 0.002), respectively. For patients with end‐stage silicosis, LTx offers significant benefits regarding pulmonary function and survival when compared to non‐LTx, and is a reliable tool to help this critical population of patients, whose only treatment option is LTx.     

An experimental study of local chemotherapy for metastatic lung tumor —Isolated lung perfusion and pulmonary artery infusion—

Purpose

We evaluated the efficacy of local chemotherapy using isolated lung perfusion (ILP) and pulmonary artery infusion (PAI) in vivo to improve prognosis for patients with metastatic lung diseases.

Material and methods

Male F344 rats were used. The left lung was isolated and chemotherapeutic agents were administrated to the isolated lung by the ILP or PAI technique. Agents used were cisplatin (CDDP) and fluorouracil (5-FU), and their levels in the perfused lung and serum were measured (renal levels were also measured in CDDP groups). The results were compared with those obtained following intravenous administration (IV). In the ILP group, the left pulmonary artery and vein were clamped during perfusion. The agents were infused from the pulmonary artery, and the perfusate was collected from the pulmonary venotomy site following flushing with saline before declamping. In the PAI group, the left pulmonary artery was clamped and perfused with 0.2 ml of the agents, pulmonary arterial flow was occluded for 20 minutes, and perfusate was not collected. Rats were sacrificed 5 minutes after declamping in both groups, and the perfused lung and blood (and also kidneys in the CDDP group) were collected for pharmacokinetic examination. Histological examination of the perfused lung was also performed. Results: In the ILP group treated with 1 mg of CDDP and PAI group treated with 0.1 mg of CDDP administration, the lung CDDP levels were significantly higher and the serum and renal CDDP levels were significantly lower than those in the IV group. In the ILP group treated with 150 mg of 5-FU and PAI group treated with 10 mg of 5-FU, the lung 5-FU levels were significantly higher than those in all IV groups and the serum 5-FU levels were lower than those in the IV group treated with 10 mg and 15 mg of 5-FU. The bronchopulmonary construction was histologically maintained in the perfused lung in each group. Conclusion: We concluded that local chemotherapy using ILP or PAI could be a safe and effective choice of therapy, and this method may be clinically applicable.