Heart-lung Block Research Articles

An Inexpensive, Reproducible Tissue Simulator for Teaching Thoracoscopic Lobectomy

Simulation is rapidly becoming an integral part of surgical education at all levels including the education of practicing surgeons in new techniques such as thoracoscopic lobectomy. Current thoracoscopic lobectomy simulator models have significant limitations including expense and requirement for specialized facilities. This study describes a novel low-cost, easily reproducible, bench top simulator. Tissue blocks consisting of a porcine heart and bilateral lungs with intact pericardium were secured from a commercially available source. The pulmonary artery and veins were statically distended with ketchup to more realistically mimic the technique of dissection and allow for simultaneous identification of technical errors. This simulator has been used at seven different industry and society sponsored thoracoscopic lobectomy training programs by more than 100 participants. Qualitative data on the performance of the model was collected from faculty and course participants. A low-cost porcine heart-lung block statically perfused with ketchup provides an inexpensive, easily reproducible model for teaching thoracoscopic lobectomy, which reasonably and accurately simulates a clinical experience.

Post-ischemic Infusion of Atrial Natriuretic Peptide Attenuates Warm Ischemia–Reperfusion Injury in Rat Lung

The serious shortage of organs for transplantation, especially lungs, has drawn increasing attention to donation after cardiac death and protection of organs against warm ischemic injury. Atrial natriuretic peptide (ANP) activates guanylate cyclase receptors and increases cyclic guanosine monophosphate (cGMP) levels, which decrease in the lung during ischemia. In this study we investigated the effect on lung ischemia-reperfusion injury of administering synthetic ANP (carperitide) at the onset of reperfusion after warm ischemia. An isolated rat lung perfusion model was used. The rats were allocated into three groups: the control group; the ANP group; and the sham group. In the control and ANP groups, the heart-lung block was exposed to 60 minutes of ischemia at 37 degrees C, and subsequently reperfused for 60 minutes. At the onset of reperfusion, either saline or ANP was added to the perfusate. In the sham group, lungs were continuously perfused without ischemia and only saline was added to the perfusate. ANP significantly reduced pulmonary vascular resistance and pulmonary edema, and improved oxygenation. It also significantly increased cGMP levels in reperfused lungs. Histologically, lungs in the ANP group showed significantly fewer signs of injury and fewer cells demonstrated apoptotic changes or single-stranded DNA than lungs in the control group. Our results indicate that ANP administered at the onset of reperfusion increases cGMP in lung tissue and attenuates warm ischemia-reperfusion injury in isolated perfused rat lung.

Protective effect of thioredoxin perfusion but not inhalation in warm ischemic-reperfused rat lungs

Background: Thioredoxin is a ubiquitous protein with anti-oxidative, anti-apoptotic, and anti-inflammatory effects. It was reported [Fukuse T, Hirata T, Yokomise H et al. Attenuation of ischaemia reperfusion injury by human thioredoxin. Thorax 1995; 50: 387–391] that rhTRX protected lungs from ischemia-reperfusion injury as a radical scavenger; however, the mechanism was not elucidated. Therefore, we investigated the effect of perfusion and inhalation of rhTRX, and the associated mechanisms, by analyzing the concentrations and molecular states of the perfused rhTRX.Materials and methods: Perfusion and inhalation studies of rhTRX were conducted with an isolated rat-lung perfusion model. The heart-lung block was perfused for 15 min and subsequently exposed to a 55-min ischemia followed by a 120-min reperfusion. Pulmonary artery pressure, weight gain, dynamic airway resistance, pulmonary compliance, and tidal volume were measured continuously. The concentrations and molecular states of the perfused rhTRX were measured.Results: A 350-μg/ml perfusion of rhTRX decreased post-ischemic pulmonary artery pressure (P < 0.05), while a 200-μg/ml perfusion did not. Throughout the experiment, the rhTRX concentrations were constant, and the rhTRX molecules were mostly dimeric. The inhalation of rhTRX showed adverse effects on the pulmonary function compared with the control group (P < 0.05).Conclusions: A 350-μg/ml perfusion, but not inhalation, of rhTRX protected rat lungs from ischemia-reperfusion injury. rhTRX was effective in dimeric form without transit to the lung tissue. rhTRX may be effective by some mechanism other than radical scavenging.

A mouse model of orthotopic, single-lung transplantation

Progress in studying acute and chronic pulmonary allograft rejection has been hampered by the lack of feasible experimental animal transplantation models. Contemporary approaches are limited by anatomic applicability (heterotopic tracheal implantation) and lack of genetic variability (rat model). To utilize the breadth of available genetic modifications in a physiologic setup, we optimized and validated a procedure of orthotopically transplanted, perfused, and ventilated single pulmonary transplantation in mice. C57BL/6 mice served as recipient, with Balb/c as donor. At time of harvest, explanted lungs were perfused with Perfadex, and the heart-lung block excised. Under 30 to 40x magnification, vessels and bronchus were cuffed. Following left thoracotomy in the recipient, hilar structures were incised and cuff-anastomosed with the corresponding donor parts. Allogeneic and syngeneic transplantations (n = 12/group) were performed with a follow-up period of 5 days and up to 90 days, respectively. The success rate of lung transplantation in mice was 87.5% (21/24). Mean cold ischemia time was 32.3 +/- 3.7 minutes, and warm ischemia time was 30.8 +/- 9.5 minutes. Deaths were due to bleeding during dissection of the hilus and/or caused by thrombosis postoperatively. Allogeneic grafts were rejected by day 5; syngeneic grafts were slightly congested but mainly unchanged up to day 90 posttransplantation. Unilateral lung transplantation in mice can be performed in a standardized and controlled fashion with low mortality, comparable to the rat. Employing transgenic and knockout mice strains, this procedure holds great promise to advance the understanding of immunologic pathways in acute and chronic rejection in a physiologic model of pulmonary transplantation.

446: Successful Subzero Non-Freezing Preservation of Rat Lungs with Supercooling Technology

Purpose: Supercooling is defined as a non-freezing state of liquid below freezing temperature. Stable supercooling at the temperature between 0°C to –10°C is achieved in a newly developed refrigerator with a power voltage of 3,000 V. We hypothesized that supercooling would reduce metabolism of organ grafts and lungs preserved in supercooling would have better physiological function than in the clinically standard storage at 4°C. Methods and Materials: We investigated in a previously published isolated rat lung perfusion model, in which physiological parameters such as tidal volume, arterial oxygen tension, and lung weight were measured. The heart-lung block was preserved for 17 hr and subsequently reperfused for 60 minutes. All animals were divided into three groups. In the supercoolng group (n 7), non-freezing preservation at -2°C was kept in a supercooling refrigerator. In the control group (n 7), the ordinary hypothermic preservation was maintained at 4°C. In the sham group (n 7), after harvesting lungs were continuously perfused without hypothermic preservation. Results: Two animals in the control group were excluded from the following analysis because of severe lung edema within 12 minutes of reperfusion. Oxygen tensions at 60 minutes of reperfusion were 101.8 2.6 in the supercooling, 58.6 10.8 in the control, and 104.4 1.9 in the fresh (mmHg). At 60 minutes, tidal volumes were 2.0 0.1 in the supercooing, 1.0 0.3 in the control, and 2.2 0.1 in the fresh (mL). The lung weight gains during the 60 minutes were 1248 56, 2983 543, and 693 69, in supercooling, in control and in fresh, respectively (mg). Throughout the experiment, oxygen tensions and tidal volumes in the supercooling and the fresh were significantly higher than the control group(p 0.001, p 0.05, respectively), and the lung weight gains in the supercooling and the fresh were significantly lower than the control (p 0.001). Conclusions: Supercooling demonstrated the superiority in hypothermic preservation of rat lungs to the standard storage of 4°C in an isolated rat lung perfusion model.

Ex-Vivo Perfusion and Ventilation of Rat Lungs From Non-Heart-Beating Donors Before Transplant

We developed an ex-vivo circuit to evaluate human lungs retrieved from non-heart-beating donors. We assessed the effect of a similar circuit on the function of transplanted rat lungs retrieved from non-heart-beating donors. One hour after death, Sprague-Dawley rat heart-lung blocks were flushed with 20 mL of cold Perfadex, stored cold for 1 hour, then warmed to 37 degrees C in a circuit perfused with Earle's crystalloid solution with or without washed porcine erythrocytes (hematocrit 12% to 15%). At 37 degrees C, lungs were ventilated for 15 minutes with alveolar gas, perfusion-cooled to 20 degrees C, flushed again with cold Perfadex, and then stored cold for 2.5 hours. The left lung was transplanted using a modified cuff technique with flow probes on the main and left pulmonary arteries. After 1 hour of reperfusion, arterial blood gases from the left pulmonary vein and wet/dry weight ratio (W/D) of both donor lungs were determined. Lungs transplanted after retrieval from heart-beating or non-heart-beating donors served as controls (n = 6 per group). Lungs gained weight in the circuit but W/D and PO2 were similar after transplantation for all groups. After transplantation, vascular resistance was higher and dynamic compliance was lower for lungs perfused in the circuit. Myeloperoxidase and conjugated diene levels were modestly elevated in lungs transplanted from non-heart-beating donors irrespective of perfusion in the circuit. Rat lungs are suitable for transplant after ex-vivo perfusion and ventilation. This model closely mimics methods used to evaluate the function of lungs retrieved from human non-heart-beating donors and can economically evaluate ex-vivo therapies for lungs retrieved from non-heart-beating donors.

In vitro study of the safety limits of bronchoscopic argon plasma coagulation in the presence of airway stents

The purpose of this study was to identify the safety limits of bronchoscopic argon plasma coagulation (APC) around indwelling airway stents. This is an experimental in vitro study simulating a patient-care environment. Uncovered and covered Nitinol (Ultraflex), uncovered and covered Wallstent and studded silicone stents were deployed in the tracheobronchial tree of a ventilated and oxygenated heart-lung block from an expired pig. APC was performed at power settings of 40 and 80 W using F(I)O(2) of 0.21, 0.40 and 1.00 and an argon gas-flow rate of 0.8 L/min through a flexible fiberoptic bronchoscope. The primary outcome was the time taken for the APC to cause stent damage. Stent damage was defined as discoloration, ignition or rupture. Airway fires involving all five stents consistently occurred in the presence of 100% oxygen at powers of 40 W and 80 W. At lower F(I)O(2) (0.21 and 0.40) silicone stents were not damaged at 40 W and 80 W. Uncovered Ultraflex stents were undamaged using 40 W at either F(I)O(2) (0.21 and 0.40), but could be damaged using both F(I)O(2) levels when the power was increased to 80 W. Covered Ultraflex and both uncovered and covered Wallstents were damaged at both power settings (40 W and 80 W) and F(I)O(2) (0.21 and 0.40) levels, with a trend towards earlier damage using higher F(I)O(2) and power. Working within the parameters identified in this study (power 40 W, F(I)O(2) 0.21, APC flow-rate 0.8 L/min), APC is a safe method for tissue devitalization and destruction and avoids the risk of airway stent ignition, especially if short bursts of APC are employed. The safety limits identified using an F(i)O(2) of 0.4, however, are also important because some patients undergoing resection may require oxygen therapy.

Protective Effect of a Nebulized β 2-Adrenoreceptor Agonist in Warm Ischemic–Reperfused Rat Lungs

It seems inevitable that non-beating-heart donors will be utilized to resolve the shortage of donors for clinical lung transplantation. The control of warm ischemia-reperfusion injury is crucial in manipulating non-beating-heart donors. We hypothesized that nebulization of a beta2-adrenoreceptor agonist, salmeterol xinafoate (SLM), during warm ischemia would increase lung tissue cyclic adenosine monophosphate (cAMP) levels, resulting in lung protection. Two studies were conducted. The first investigated the effect of SLM nebulization during ischemia on pulmonary ischemia-reperfusion injury, using an isolated rat lung-perfusion model. The heart-lung block was excised with cannulation of the pulmonary artery and vein, exposed to 55 minutes of ischemia at 37 degrees C, and subsequently reperfused for 60 minutes. Several parameters were measured during reperfusion. In the second study, to measure changes in lung tissue cAMP levels during warm ischemia with or without SLM nebulization, rat lungs were harvested and exposed to 60 minutes of warm ischemia with ventilation. Salmeterol xinafoate nebulization significantly decreased the pulmonary shunt fraction, airway resistance, and pulmonary vascular resistance. It also inhibited pulmonary edema throughout the reperfusion period. Lung tissue cAMP was effectively maintained by SLM nebulization at the end of reperfusion. Myeloperoxidase activity in the lungs was decreased significantly by SLM nebulization. Lung tissue cAMP levels decreased during the 60 minutes of warm ischemia, but increased with SLM nebulization (p < 0.01). Our results confirmed that SLM nebulization during warm ischemia maintained lung tissue cAMP levels, resulting in the alleviation of pulmonary warm ischemia-reperfusion injury.

Transplantation at 100 Years: Alexis Carrel, Pioneer Surgeon

n December 23, 1954, Ronald Herrick became the first ealthy human being to subject himself to a major urgical procedure for the benefit of someone other than imself. He was the donor of a kidney to his identical win brother, Richard, who was dying of end-stage renal isease. His brother’s donated kidney allowed Richard to urvive for another 8 years [1]. The surgeon, Dr Joseph urray of the Peter Brigham Hospital in Boston, had one extensive preliminary experimental work and coninued to be a leader not only in clinical transplantation, ut also in the study of the immune phenomena surounding transplantation. Dr Murray, along with E. Donall Thomas, was awarded the Nobel Prize in Physiology r Medicine in 1990, “for their discoveries concerning rgan and cell transplantation in the treatment of human isease” [2]. Last year, the semi-centennial anniversary of the proedure was widely celebrated as the beginning of clinical rgan transplantation. Although the 1954 procedure aunched clinical transplantation, the science of organ ransplantation actually began a half-century earlier. The ear 2005 marks the centennial anniversary of Alexis arrel’s publication of his first article on successful organ ransplantation in October 1905 [3]. The critical technical prerequisite for successful translantation surgery was the development of techniques or suturing blood vessels. Such methods had not been eveloped yet in 1894 when the president of France, Sadi arnot, was assassinated in Lyon. Carnot was stabbed in he abdomen and bled to death from a laceration of the ortal vein. Surgical opinion held that the president ould not have been saved because of the nature of his njury. A young medical student at the University of yon, Alexis Carrel, argued to the contrary that Carnot ould have been saved if surgeons could repair blood essels as they repaired other tissues. In 1896, Carrel was n intern at Lyon’s Hotel Dieu, and he was aware that atthieu Jaboulay at the University of Lyon had successully repaired a divided carotid artery experimentally, sing everting interrupted mattress sutures. However, is method did not work in the repair of small blood essels. In that year, Carrel started his own experiments, nd before long his work gained local notoriety. He ecognized that extremely fine needles and thread were eeded, and he found what he needed, but not in surgical

Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced lung injury*

To assess the influence of massive brain injury on pulmonary susceptibility to injury attending subsequent mechanical or ischemia/reperfusion stress. Prospective experimental study. Animal research laboratory. Twenty-four anesthetized New Zealand White rabbits randomized to control (n = 12) or induced brain injury (n = 12) group. After randomization, brain injury was induced by inflation of an intracranial balloon-tipped catheter, and animals were ventilated with a tidal volume of 10 mL/kg and zero end-expiratory pressure for 120 mins. Following heart-lung block extraction, isolated and perfused lungs were subjected to injurious ventilation with peak airway pressure 30 cm H2O and positive end-expiratory pressure 5 cm H2O for 30 mins. No difference was observed between groups in gas exchange, lung mechanics, or hemodynamics during the 2-hr in vivo period following induction of brain injury. However, after 30 mins of ex vivo injurious mechanical ventilation, lungs from the brain injury group showed greater change in ultrafiltration coefficient, weight gain, and alveolar hemorrhage (all p < .05). Massive brain injury might increase lung vulnerability to subsequent injurious mechanical or ischemia-reperfusion insults, thereby increasing the risk of clinical posttransplant graft failure.

IL-1β in bronchial lavage fluid is a non-invasive marker that predicts the viability of the pulmonary graft from the non-heart-beating donor

Background Viability testing of the pulmonary graft retrieved from the non-heart-beating donor (NHBD) is mandatory for successful outcome after lung transplantation. Functional assessment by ex vivo reperfusion, however, remains a cumbersome procedure. In this study, therefore, we wanted to investigate the possible value of the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) measured in bronchial lavage fluid (BLF) in predicting functional outcome of the pulmonary graft after reperfusion. Methods Domestic pigs (29.9 ± 0.56 kg) were sacrificed and divided in 5 groups ( n = 5/group). In the non-ischemic group (NHBD-0), the heart-lung block was explanted immediately. In the other groups the animals were left untouched with increasing time intervals (1 hour = NHBD-1; 2 hours = NHBD-2; 3 hours = NHBD-3). Thereafter both lungs were cooled topically via chest drains up to a total ischemic interval of 4 hours. Finally, in the heart-beating donor group lungs were flushed and stored for 4 hours (4°C) [HBD]. BLF samples were taken from the right lung in all groups after explantation for measurement of IL-1β and TNF-α and the left lung was prepared for evaluation in an isolated reperfusion circuit. Haemodynamic, aerodynamic and oxygenation parameters were measured. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. Results Graft function deteriorated with increasing time intervals after death. A strong correlation was found between the increase of IL-1β concentration measured in BLF and the increase in pulmonary vascular resistance (r = 0.80), mean airway pressure (r = 0.74) and wet-to dry weight ratio (r = 0.78); ( p < 0.0001, for all parameters). No significant differences in TNF-α levels in BLF were observed amongst groups ( p = 0.933). Conclusions IL-1β in BLF prior to reperfusion correlated well with graft function and may therefore be a useful, non-invasive marker that can predict the viability of the pulmonary graft from the NHBD.

Lung Transplantation in Rats: a Viable Experimental Model

To incorporate a new fast, safe, and reversible anesthetic procedure into the experimental model of lung transplantation (LT) using a cuff technique originally described by Mizuta. Eighty-eight Sprague-Dawley rats were used in the experimental model. Thirty left LTs were performed, using 60 rats. The donor heart-lung block was excised by median sternotomy with dissection of the left lung and cuffs (intravenous catheters cut into 3-mm sections) were put in place. The left lung was implanted in the recipient by lateral thoracotomy using the cuffs for anastomoses. The duration of surgery and postoperative complications were recorded. Also noted were signs of ischemia-reperfusion injury, and acute rejection of the transplanted lung. We discarded lungs excised from 8 animals when developing the experimental model. Transplants could not be completed in 10 rats due to technical problems, despite satisfactory excision. Of the rats who received a transplant, 4 died in the first 24 hours and 26 survived to 48 hours. They were then killed and examined. The state of the anastomoses was good and signs of ischemia-reperfusion injury, as well as acute rejection were observed in the parenchyma of the transplanted lung. LT with cuffs in rats is a valid, reliable, reproducible, and cheap model for studying ischemia-reperfusion injury and rejection in LT. The surgical technique is complex, requiring experienced surgeons and a long learning process. Modification of the technique to more closely resemble the surgical procedure in humans is possible, thus facilitating interpretation and allowing more reliable extrapolation to humans.

Pulmonary preservation effect of nitroglycerine in isolated rat lung reperfusion model

Purpose Though nitric oxide has many favorable protective effects on donor lungs, it may also have cytotoxic side effects. In this regard, we investigated whether administration of nitroglycerine, a nitric oxide donor, could minimize ischemia-reperfusion injury in an isolated rat lung reperfusion model. Materials and methods Thirty-five Sprague-Dawley rats were used for this experiment. The nitroglycerine (NTG) group ( n = 18) received the drug intravenously and the 17 control group hosts were treated with the same amount of normal saline. The heart-lung block was retrieved, weighed, and maintained in University of Wisconsin solution for 24 hours at 10°C. Reperfusion was performed using human blood diluted in Krebs-Hensleit solution for 60 minutes. Peak inspiratory pressure, pulmonary artery pressure, and blood gas analysis were performed. After 60 minutes of reperfusion, the amount of protein in bronchoalveolar lavage (BAL) fluid and the myeloperoxidase (MPO) activity in the lung were measured. Results There were no major statistical differences between the two groups in peak inspiratory pressure and pulmonary artery pressure, but the NTG group maintained lower pulmonary artery pressure during the whole period of reperfusion. Oxygen tension in the NTG group was significantly higher, whereas there were no differences in carbon dioxide tension, BAL fluid, protein, or MPO activity. Conclusion Administration of NTG before donor lung preservation resulted in better lung protection, a possible strategy for clinical application.

Ultrastructural evaluation of the protective effect of nitroglycerin in preservation-reperfusion injury of rat lungs

Aim of study Nitric oxide (NO) has been reported as a favorable protective supplement in donor lung preservation, but related ultrastructural studies are rare in the literature. This study was performed to assess the ultrastructural changes and to evaluate the protective effect of NO as donor nitroglycerin (NTG) treatment of ischemia-reperfusion injury in rat lungs. Materials and methods Fifteen Sprague-Dawley rats weighing 300 to 350 g were used in this study. The NTG group (n = 5) used intravenous administration followed by mixture in the University of Wisconsin (UW) solution. For the non-NTG group (n = 5), we injected the same amount of normal saline intravenously followed by admixture in the UW solution. The heart-lung blocks were removed, weighed, and kept in UW solution for 24 hours at 10°C. Reperfusion using human blood diluted in Krebs-Hensleit solution was done for 60 minutes. For the control group (n = 5), we injected the same amount of normal saline intravenously, and removed the lungs with no preservation and reperfusion procedures. Results The non-NTG group showed multiple patchy areas of alveolar collapse with marked swelling and destruction of type I epithelial cells, loss of type II cell surfactant granules, endothelial swelling and papillary projection, interstitial edema, and alveolar macrophages with active phagocytosis of the destroyed materials. The NTG group showed similar ultrastructural changes, but in a lesser severity compared with the non-NTG group. Conclusion Administration of the NTG reduced the ischemia-reperfusion injury in the rat donor lungs. Ultrastructural examination was an effective tool to evaluate the protective effect of NTG in ischemia-reperfusion procedures of donor lungs.

Cytomegalovirus antibody status of donor/recipient does not influence the incidence of bronchiolitis obliterans syndrome in lung transplantation

Background: We have previously reported that prophylaxis for cytomegalovirus (CMV) infection does not influence the incidence of bronchiolitis obliterans syndrome (BOS) at 2 years. The effect of CMV infection (without evidence of disease) on BOS is still not well understood. Moreover, the incidence and risk factors for development of BOS in CMV-antibody-negative donor/recipient matches in lung transplantation have not been described. The aim of this study is to determine the incidence of BOS in lung transplant patients with CMV-antibody-negative (−) donors (D) and recipients (R), and to evaluate the risk factors that predispose to BOS in this sub-group. Method: A retrospective study of data from the transplant database of our center was performed. All single-lung (SL), double-lung (DL) and heart–lung block (HL) transplant patients who survived >2 years post-transplant were included in the study group. They were grouped as follows: D −/R −, n = 102; D −/R +, n = 70; D +/R −, n = 33, and D +/R +, n = 92. Results: The 3-year BOS-free survival rates were 65%, 56%, 58% and 67%, respectively, and the incidence rates of BOS at 5 years post-transplant in the different groups were 57%, 62%, 78% and 55% ( p > 0.05). In the D −/R − group, the significant risk factor for developing BOS was three or more episodes of acute rejection ( p = 0.02). The mean numbers of acute rejection episodes per 100 patients-days within the first 6 months were 1.28, 1.06, 0.50 and 1.11 ( p < 0.001 overall) for the four groups, respectively. Conclusion: Although CMV is believed to be a risk factor for BOS, its absence did not affect the occurrence or incidence of BOS in lung transplant patients. The main risk factor for BOS in the CMV-antibody-negative population remains the number of acute rejection episodes within the first 6 months after transplantation.

Maternal and foetal outcome following pregnancy after intrathoracic organ transplantation: single centre experience in 21 patients

Between 1987 and 2000, 21 patients who underwent intrathoracic organ transplantation conceived on 29 occassions. Transplants performed included Heart-Lung block (10), Heart transplant(8), Bilateral lung transplants (2) and Single lung transplantation (2). Mean age at transplantation was 23.2 years (range = 14-33) and at the time of conception was 29.0 years (range = 20.5-37). 16 patients (76.2%) in this series are currently alive. The outcome of pregnancy was Full term delivery in 11(38%), Live pre-term deliveries in 4 (13.8%), Miscarriages in 7(24.1%), 3rd trimester Intrabsaerine deaths in 2 (6.9%) and 1st trimester Medical termination in 5 (17.24%) instances. Immunosuppression included Cyclosporine and Azathioprine except in 1patient who had FK506 in addition. Prednisolone was used only in 12 patients (57.14%). Though of the 29 conceptions, only 3 (10.34%) were complicated by biopsy-proven rejection, there was evidence of significant graft dysfunction (Lung) in further 3 patients during pregnancy. None of the patients who had full term delivery had any rejection episode during the 1st trimester. The follow-up period of children born (full term and pre-term) ranges from 2.5-15 years. There has been no evidence of immunocompromise in children born to these mothers. None of the foetuses had any gross congenital malformations at birth or at autopsy.

Effect of Adenosine Triphosphate–Sensitive Potassium Channel Openers on Lung Preservation

ATP-sensitive potassium channel (KATP) openers have been proven to be involved in ischemic preconditioning, which protects ischemic tissue. However, the effect of KATP openers on ischemia-reperfusion injury of the lungs remains unknown. We investigated whether a KATP opener, pinacidil, can attenuate ischemia-reperfusion injury using an ex vivo rat lung model. Heart-lung blocks were flushed and preserved with phosphate-buffered saline (control group) or with one of the solutions containing pinacidil (pinacidil group) or pinacidil + glibenclamide (a KATP blocker) (glibenclamide group). The control and glibenclamide groups showed significantly higher values with respect to shunt fraction, pulmonary arterial pressure, and peak inspiratory pressure than the pinacidil group. The concentrations of total adenine nucleotides and ATP in the lung after reperfusion became significantly lower in the control and glibenclamide groups than in the fresh group. Lipid peroxidation of the lungs increased significantly in the control and glibenclamide groups after reperfusion. State 3 mitochondrial respiration and State 3/4 ratios of mitochondrial respiration were significantly decreased in the lungs of the control and glibenclamide groups. These findings suggested that KATP openers would maintain the mitochondrial respiratory function during lung preservation, prevent lipid peroxidation after reperfusion, and attenuate ischemia-reperfusion injury.

Nd-YAG Laser Damage to Metal and Silicone Endobronchial Stents: Delineation of Margins of Safety Using an In Vitro Experimental Model

Study objectiveTo identify margins of safety within which bronchoscopic Nd-YAG laser resection can be performed without damaging indwelling tracheobronchial stents. DesignExperimental in vitro study simulating a patient-care environment. MethodsUncovered and covered metal Wallstent (Schneider; Zurich, Switzerland) and Dumon (Bryan Corporation; Woburn, MA) silicone stents were deployed in the tracheobronchial tree of a ventilated and oxygenated (fraction of inspired oxygen, 40%) heart-lung block of a dead canine. Rigid bronchoscopic Nd-YAG (1,064 nm) laser procedures were performed in order to deliver laser energy using fiber-to-target distances of 10 mm and 20 mm, and noncontact, continuous-mode, 1-s pulses at power settings of 10 W, 30 W, and 40 W. The major outcome measure was laser-induced stent damage, defined as discoloration, ignition, or breakage. This was assessed using six power densities: 75 W/cm2, 172 W/cm2, 225 W/cm2, 300 W/cm2, 518 W/cm2, and 690 W/cm2. ResultsThe uncovered Wallstent and the silicone stent remained intact at power densities of 75 W/cm2 (10 W, 20 mm) and 172 W/cm2 (10 W, 10 mm), but were damaged at power densities > 225 W/cm2 (30 W, 20 mm). The covered Wallstent was damaged at all power densities tested. ConclusionUncovered Wallstent and silicone stents are not damaged when Nd-YAG laser energy is delivered using power densities ≤ 172 W/cm2 (10 W, 10 mm). Covered Wallstents, however, had a high likelihood of ignition at all power densities studied.

Transplantation of lungs from a non-heart-beating donor

In animals, we have previously done successful lung transplantations using organs from non-heart-beating donors. We have also developed an ex-vivo system of assessing the function of such organs before transplantation. The next stage was to try the technique in human beings. Bearing in mind the sensitive ethical issues involved, our first aim was to find out what procedures would be acceptable, and to use the results to guide a clinical lung transplantation from a non-heart-beating donor. The ethical acceptability of the study was gauged from the results of a broad information programme directed at the general public in Sweden, and from discussions with professionals including doctors, nurses, hospital chaplains, and judges. The donor was a patient dying of acute myocardial infarction in a cardiac intensive-care unit after failed cardiopulmonary resuscitation. The next of kin gave permission to cool the lungs within the intact body, and intrapleural cooling was started 65 min after death. Blood samples were sent for virological testing and cross matching. The next of kin then had time to be alone with the deceased. After 3 h, the body was transported to the operating theatre and the heart-lung block removed. The lungs were assessed ex vivo, and the body was transported to the pathology department for necropsy. No contraindications to transplantation were found, and the right lung was transplanted successfully into a 54-year-old woman with chronic obstructive pulmonary disease. The donor lung showed excellent function only 5 min after reperfusion and ventilation, and during the first 5 months of follow-up, the function of the transplanted lung has been good. About half the deaths in Sweden are caused by cardiac and cerebrovascular disease. This group could be a potential source of lung donors. When all hospitals and ambulance personnel in Sweden have received training in non-heart-beating lung donation, we hope that there will be enough donor lungs of good quality for all patients needing a lung transplant.

Bronchiolitis obliterans with organizing pneumonia: possible association with human herpes virus-7 infection after lung transplantation

transplant database of the centre was carried out. All single lung (SL), double lung (DL) and heart-lung block (HL) transplant patients who survived over 2 years post transplant were included in the study group. They were grouped as follows: A 5 D-/R(n5102), B 5 D-/R1 (n570), C 5 D1/R(n533) and E 5 D1/R1 (n592). The respective incidence of BOS in the different groups was 43.1%, 45.7%, 51.5% and 47.8% (p50.32). The 3-year BOS free survival was 65%, 56%, 58% and 67% respectively (p.0.05). In group A, the significant risk factors for developing BOS were three or more episodes of acute rejection (p50.02) and non-CMV pulmonary infection (p50.03). The mean number of acute rejection episodes per 100 patients days within the first six months were 1.28 (group A), 1.06 (group B), 0.50 (group C) and 1.11 (group E) [p,0.05]. Conclusion: Although CMV has been shown to be a risk factor for BOS, its absence did not preclude lung transplant patients from developing BOS. Moreover, absence of CMV was associated with an increase in the number of acute rejection episodes within the first transplant year. However, this could be accounted for by changes in frequency of acute rejection over time. Moreover, this may also reflect the non-uniformity of the pathological processes that are grouped as BOS.