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Objectives: Detecting particle flow from the airways by none invasively online analysing technique might serve as an additional tool to monitor mechanical ventilation. In the present study we used a customised Pexa (Particles in Exhaled Air), which is an optical particle counter for airway monitoring of particle flow in exhaled air. Positive end expiratory pressure (PEEP) is often used as a tool during recruitment manoeuvre and the aim of this study was to investigate the impact of different levels of PEEP on particle flow in exhaled in an experimental setting.Methods: Five animals received a gradual increase of 5 PEEP to a maximum of 25 PEEP during VCV. Measurements were done before every increase in PEEP in fully anaesthetised domestic pigs. The particle count along with vital parameters and ventilator settings were collected continuously. The particle sizes measured was between 0.41 µm and 4.55 µm.Results: All animals had a significant increase in particle count going from all increased levels of PEEP and back down to baseline PEEP of 5 cmH2O. Here shown with PEEP 15 that had a mean particle count of 401 ± 122 particles compared to after release of PEEP back to 5 with a mean particle count of 5968 ± 1784 (p2O.Conclusions: In the present study significant increase in particle count was seen when releasing PEEP back to baseline compared to all levels of PEEP. This finding may indicate that this technique can give diagnostic possibilities for monitoring lung function during mechanical ventilation.

Acute respiratory distress syndrome (ARDS) is a common cause of death in the intensive care unit, with mortality rates of ~30–40%. To reduce invasive diagnostics such as bronchoalveolar lavage and time-consuming in-hospital transports for imaging diagnostics, we hypothesized that particle flow rate (PFR) pattern from the airways could be an early detection method and contribute to improving diagnostics and optimizing personalized therapies. Porcine models were ventilated mechanically. Lipopolysaccharide (LPS) was administered endotracheally and in the pulmonary artery to induce ARDS. PFR was measured using a customized particles in exhaled air (PExA 2.0) device. In contrast to control animals undergoing mechanical ventilation and receiving saline administration, animals who received LPS developed ARDS according to clinical guidelines and histologic assessment. Plasma levels of TNF-α and IL-6 increased significantly compared with baseline after 120 and 180 min, respectively. On the other hand, the PFR significantly increased and peaked 60 min after LPS administration, i.e., ~30 min before any ARDS stage was observed with other well-established outcome measurements such as hypoxemia, increased inspiratory pressure, and lower tidal volumes or plasma cytokine levels. The present results imply that PFR could be used to detect early biomarkers or as a clinical indicator for the onset of ARDS.

In severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) is a life‐prolonging treatment, especially among COVID‐19 patients. Evaluation of lung injury progression is challenging with current techniques. Diagnostic imaging or invasive diagnostics are risky given the difficulties of intra‐hospital transportation, contraindication of biopsies, and the potential for the spread of infections, such as in COVID‐19 patients. We have recently shown that particle flow rate (PFR) from exhaled breath could be a noninvasive, early detection method for ARDS during mechanical ventilation. We hypothesized that PFR could also measure the progress of lung injury during ECMO treatment. Lipopolysaccharide (LPS) was thus used to induce ARDS in pigs under mechanical ventilation. Eight were connected to ECMO, whereas seven animals were not. In addition, six animals received sham treatment with saline. Four human patients with ECMO and ARDS were also monitored. In the pigs, as lung injury ensued, the PFR dramatically increased and a particular spike followed the establishment of ECMO in the LPS‐treated animals. PFR remained elevated in all animals with no signs of lung recovery. In the human patients, in the two that recovered, PFR decreased. In the two whose lung function deteriorated while on ECMO, there was increased PFR with no sign of recovery in lung function. The present results indicate that real‐time monitoring of PFR may be a new, complementary approach in the clinic for measurement of the extent of lung injury and recovery over time in ECMO patients with ARDS., Particle flow rate (PFR) used in conjunction with mechanical ventilation can be used to monitor lung injury during ECMO treatment in animals with LPS induced ARDS and in humans with COVID‐19 induced ARDS. The present results indicate that real‐time monitoring of PFR may be a new, complementary approach in the clinic for measurement of the extent of lung injury and recovery over time in ECMO patients with ARDS.

Despite improvements, lung transplantation (LTx) remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine filtration as a means of restoring ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 12 donor pigs. Lungs were then treated with or without cytokine filtration during ex vivo lung perfusion (EVLP) and post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine filtration was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.

Despite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.

Background Different mechanical ventilation settings are known to affect lung preservation for lung transplantation. Measurement of particle flow in exhaled air may allow online assessment of the impact of ventilation before changes in the tissue can be observed. We hypothesized that by analyzing the particle flow, we could understand the impact of different ventilation parameters. Methods Particle flow was monitored in vivo, post mortem, and in ex vivo lung perfusion (EVLP) in six porcines with the Pexa (particles in exhaled air) instrument. Volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) were used to compare small versus large tidal volumes. The surfactant lipids dipalmitoylphosphatidylcholine (DPPC) and phosphatidylcholine (PC) were quantified by mass spectrometry. Results In vivo the particle mass in VCV1 was significantly lower than in VCV2 (p = 0.0186), and the particle mass was significantly higher in PCV1 than in VCV1 (p = 0.0322). In EVLP, the particle mass in VCV1 was significantly higher than in PCV1 (p = 0.0371), and the particle mass was significantly higher in PCV2 than in PCV1 (p = 0.0127). DPPC was significantly higher in EVLP than in vivo. Conclusions Here, we introduce a new method for measuring particle flow during mechanical ventilation and confirm that these particles can be collected and analyzed. VCV resulted in a lower particle flow in vivo but not in EVLP. In all settings, large tidal volumes resulted in increased particle flow. We found that DPPC was significantly increased comparing in vivo with EVLP. This technology may be useful for developing strategies to preserve the lung and has a high potential to detect biomarkers.

Objective Lung transplantation is hampered by the lack of organs resulting in deaths on the waiting list. The usage of donation after circulatory death (DCD) lungs would dramatically increase donor availability. The most optimal organ preservation method, and the need for antithrombotic and fibrinolytic treatment to prevent thrombosis in the donor lungs is currently on debate. The present study investigated, in a simulated clinical DCD situation, whether the addition of alteplase in the flush-perfusion solution at the time of pulmonary graft harvesting could prevent thrombosis in the donor lung and thereby improve pulmonary graft function. Methods Twelve Swedish domestic pigs were randomized into two groups. All animals underwent ventricular fibrillation and were then left untouched for 1 h after declaration of death. None of the animals received heparin. The lungs were then harvested and flush-perfused with Perfadex® solution and the organs were then stored at 8 °C for 4 h. In one group alteplase was added to the Perfadex® solution (donation after cardiac death with alteplase (DCD-A)) and in the other, it was not (DCD). Lung function was evaluated, using ex vivo lung perfusion (EVLP), with blood gases at different oxygen levels, pulmonary vascular resistance (PVR), lung weight, and macroscopic appearance. Results During EVLP, there were no significant differences between groups in PaO2 at any investigated FiO2 level (1.0, 0.5, or 0.21). At FiO2 1.0, the PaO2 in the DCD and DCD-A was 51.7 ± 2.05 kPa and 60.3 ± 3.67 kPa, respectively (p = 0.1320). There were no significant differences between groups PVR levels, in the DCD (372 ± 31 dyne x s/cm5) and in the DCD-A (297 ± 37 dyne x s/cm5) groups (p = 0.1720). There was no significant difference between groups in macroscopic appearance. Conclusions All the lungs showed excellent blood gases after EVLP, and they all meet the criteria's for clinical lung transplantation. The use of alteplase did not seem to have any obvious benefit to the donor lungs in a DCD situation. The donor lungs treated with alteplas showed slightly better blood gases and slightly lower PVR compared to the group without alteplas, however the difference was not significant. DCD appears to be a safe and effective method to expand the donor pool.

Background In 2006 and 2007 we performed double lung transplantation with marginal donor lungs assessed and reconditioned by Ex Vivo Lung Perfusion (EVLP), using a technique developed by Professor Stig Steen. Here we present a 10-year follow-up comparing the outcomes of lung transplantations performed at our clinic using EVLP lungs vs. conventional lungs. Method Between 2006 and 2007, 21 patients (6 EVLP, 15 conventional) underwent double lung transplantation (LTx) with follow-up on May 2017 at Lund University Hospital, Sweden. Pulmonary function was measured at 3/6/12 months, and annually thereafter for a period of 10 years in addition to survival and freedom from chronic lung allograft dysfunction (CLAD) being analyzed. Results Regarding Forced Expiratory Volume in 1 s (FEV1) and 6MWT at 3, 6, and 12 months and annually thereafter, no difference in median FEV1 nor 6MWT was found for EVLP-LTx vs. conventional-LTx (p > 0.05). No difference was shown in post-operative survival between EVLP-LTx vs. conventional LTx for patients with an overall survival up to 10-years (p > 0.05). The same pattern was shown in sub analyses for patients with a limited survival up to 1 and 5 years (p > 0.05). Conclusion No superiority was found in conventional-LTx over EVLP-LTx, neither in long-term survival nor pulmonary function. No difference in CLAD-free survival was seen between the two groups. We believe that EVLP is a safe and effective method to use in LTx, greatly increasing the donor pool by improving marginal lungs and providing an objective assessment of the viability of marginal donor lungs.

Objectives Noninvasive online monitoring of different particle flows from the airways may serve as an additional tool to assess mechanical ventilation. In the present study, we used a customised PExA, an optical particle counter for monitoring particle flow and size distribution in exhaled air, to analyse airway particle flow for three subsequent days. We compared volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) and performed recruitment manoeuvres (RM). Methods Six animals were randomised into two groups: half received VCV before PCV and the other half received PCV before VCV. Measurements were taken daily for 1 h in each mode during three subsequent days in six fully anaesthetised domestic pigs. A RM was performed twice daily for 60 s at positive end-expiratory pressure (PEEP) of 10, 4 breaths/min and inspiratory-expiratory ratio (I:E) of 2:1. Measurements were taken for 3 min before the RM, 1 min during the RM and for 3 min after the RM. The particle sizes measured were between 0.48 and 3.37 μm. Results A significant stepwise decrease was observed in total particle count from day 1 to day 3, and at the same time, an increase in fluid levels was seen. Comparing VCV to PCV, a significant increase in total particle count was observed on day 2, with the highest particle count occurring during VCV. A significant increase was observed comparing before and after RM on day 1 and 2 but not on day 3. One animal developed ARDS and showed a different particle pattern compared to the other animals. Conclusions This study shows the safety and useability of the PExA technique used in conjunction with mechanical ventilation. We detected differences between the ventilation modes VCV and PCV in total particle count without any significant changes in ventilator pressure levels, FiO2 levels or the animals’ vital parameters. The findings during RM indicate an opening of the small airways, but the effect is short lived. We have also showed that VCV and PCV may affect the lung physiology differently during recruitment manoeuvres. These findings might indicate that this technique may provide more refined information on the impact of mechanical ventilation.

Purpose Despite improvements in lung transplantation (LTx), severe primary graft dysfunction (PGD) remains the leading cause of early mortality. In addition, a major challenge to LTx as a therapy, is the scarcity of donor organ. One major reason for rejecting a lung donor offer is acute lung injury in fear for severe PGD. To increase the number of donor organs, the possibilities of repairing damaged lungs is appealing. Cytokine filtration has shown to have an immunomodulation capacity and might therefore increase the tolerability towards the donor organ. Methods In the present study we induce acute respiratory distress syndrome (ARDS) using lipopolysaccharide (LPS) in donor pigs. Lungs where then treated with or without a cytokine filtration system in two steps. The first treatment step occurs during the use of ex vivo lung perfusion (EVLP). The left lung was subsequently transplanted, and treatment step two was initiated using ex vivo hemoperfusion in the recipient. The transplanted lung was thereafter evaluated after a right pneumonectomy to evaluate the impact on PGD at 48 hours. Figure 1) Overview. Figure 2a) Filtration EVLP 2b) Hemoperfusion recipient Results All pulmonary grafts had moderate to severe ARDS at the initiation of EVLP. Over the course of EVLP, the treated lungs increased their gas exchange capacity.The treated group required significantly less inotropic support post-transplantation and showed improved hemodynamic stability compared to the control group. During the first day post-transplantation no significant difference could be seen in the gas exchange between the groups. During the second day, however, and especially after the right pneumonectomy, a significant increase in gas exchange could be seen in the treated group compared to the controls. Conclusion Hemoperfusion post transplantation using cytokine filtration did regenerate lung function in ARDS injured donor lungs and did significantly reduced PGD.

OBJECTIVES The use of donation after cardiac death (DCD) to overcome organ shortage is slowly moving into the clinic. In this study, we compare the protective effect of warm ischaemia versus cold ischaemia on thrombotic formation in non-heparinized pulmonary grafts. METHODS Twelve Landrace pigs were randomized into two groups: warm ischaemia and cold ischaemia. Ventricular fibrillation without the administration of heparin was induced to mimick an uncontrolled DCD situation. The animals were then exposed to either 1 h of cold ischaemia (insertion of drain and installation of cold fluid in the pleuras) or warm ischaemia (body temperature). After 1 h, the pulmonary artery was opened and the pulmonary arterial branches were then macroscopically studied for thrombotic material. RESULTS After 60 min, the temperature was 36.6 ± 0.0°C in the warm ischaemic group and 14.6 ± 0.1°C in the cold ischaemic group (P < 0.001). In the warm ischaemic group, no thrombotic material could be found in the pulmonary artery in the animals examined and in the cold ischaemic group 6.8 ± 0.2 ml thrombotic material was found in the pulmonary artery (P < 0.001). In the warm ischaemic group, no thrombotic material could be found in the arterial branches of the pulmonary artery and in the cold ischaemic group 2.3 ± 0.1 ml thrombotic material was found in the arterial branches of the pulmonary artery (P < 0.001). CONCLUSIONS Warm ischaemia rather than cold ischaemia seems to protect the pulmonary graft from thrombosis in uncontrolled non-heparinized DCD pigs.

Objectives: We previously described and showed that the method for cardiac de-airing involving: (1) bilateral, induced pulmonary collapse by opening both pleurae and disconnecting the ventilator before cardioplegic arrest and (2) gradual pulmonary perfusion and ventilation after cardioplegic arrest is superior to conventional de-airing methods, including carbon dioxide insufflation of the open mediastinum. This study investigated whether one or both components of this method are responsible for the effective de-airing of the heart. Methods: Twenty patients scheduled for open, left heart surgery were randomized to two de-airing techniques: (1) open pleurae, collapsed lungs and conventional pulmonary perfusion and ventilation; and (2) intact pleurae, expanded lungs and gradual pulmonary perfusion and ventilation. Results: The number of cerebral microemboli measured by transcranial Doppler sonography was lower in patients with open pleurae 9 (6-36) vs 65 (36-210), p=0.004. Residual intra-cardiac air grade I or higher as monitored by transesophageal echocardiography 4-6 minutes after weaning from cardiopulmonary bypass was seen in few patients with open pleurae 0 (0%) vs 7 (70%), p=0.002. Conclusions: Bilateral, induced pulmonary collapse alone is the key factor for quick and effective de-airing of the heart. Gradual pulmonary perfusion and ventilation, on the other hand, appears to be less important.

Objective Systemic effects of carbon dioxide (CO 2 ) insufflation during left-sided cardiac surgery were evaluated in a prospective randomized study, with regard to acid–base status, gas exchange, cerebral hemodynamics, and red blood cell morphology. Methods Twenty patients undergoing elective left-sided cardiac surgery were randomized to de-airing procedure either by CO 2 insufflation technique (CO 2 group, n = 10) or by Lund technique without CO 2 insufflation (Lund group, n = 10). Groups underwent assessment of acid–base status by intermittent arterial blood gases and in-line blood gas monitoring. Capnography was used to determine volume of CO 2 produced. Cerebral hemodynamics was measured by transcranial Doppler sonography and near-infrared spectroscopy. Red cell morphology from cardiotomy suction and vent tubing was studied by scanning electron microscopy. Results Patients in the CO 2 group consequently developed significantly higher levels of hypercapnia with a concomitant increase in the volume of CO 2 produced despite significantly higher oxygenator gas flows compared with the Lund group. Effects on cerebral hemodynamics were observed in the CO 2 group with significantly higher blood flow velocities in the middle cerebral artery and higher regional cerebral saturation. Red blood cell damage was observed in the CO 2 group by scanning electron microscopy (97% in CO 2 group vs 18% in Lund group). Conclusions Insufflation of CO 2 into the cardiothoracic wound cavity during left-sided cardiac surgery can induce hypercapnic acidosis and increased cerebral blood flow and local blood cell damage. These systemic effects should be monitored by in-line capnography and acid–base measurements for early and effective correction by increase in gas flows to the oxygenator.

It has been debated whether or not heparin infusion before or after non-heart-beating donors are declared dead improves the quality of pulmonary grafts. In clinical lung transplantation with heart-beating donors (HBDs) heparin is routinely infused prior to organ harvesting since it is believed to improve pulmonary grafts by minimizing thrombosis formation in the pulmonary grafts. Here, we raise the question of whether or not the use of heparin in HBDs improves the quality of the pulmonary grafts.Twelve landrace pigs were divided into two groups of six animals; heparin was given prior to lung harvesting in one group, while the other group did not receive any heparin. The lungs were evaluated using an ex vivo lung perfusion (EVLP) method.No significant difference in arterial oxygen partial pressure (PaO2) was observed between the two groups at an inspired oxygen fraction (FiO2) of 1.0 (mean 69.2 kPa, range 46.1-77.0 in the non-heparin group, and 61.6 kPa, range 47.9-71.4 in the heparin group, p = 0.44), neither in pulmonary vascular resistance: mean 543 ((dyne × s)/cm(5)) (range 280-615) in the non-heparin group and 533 ((dyne × s)/cm(5)) (320-762) in the heparin group (p = 0.99).Heparin did not seem to improve pulmonary graft function in our animal model using conventional HBDs.

Background: The method of ex vivo lung perfusion (EVLP) has been suggested as a reliable means of differentiating between “good” and “poor” pulmonary grafts in marginal donors as, when grafts identified as good by this method are transplanted, the results do not differ from those using lungs fulfilling standard criteria. The EVLP method is also thought to improve pulmonary grafts by reducing lung edema and eliminating lung atelectasis. In the present study, we investigated whether the pulmonary graft could be further improved by extending the duration of EVLP. Methods and Materials: Six Landrace pigs were used. The lungs were reconditioned and evaluated, using the EVLP method, as double lungs. After the initial evaluation, EVLP was continued for a further 90 minutes. Results: The arterial oxygen level (pO2) was 60.8 ± 4.8 kPa after the standard 60 minutes of EVLP and 67.1 ± 2.2 kPa after 150 minutes (p = 0.48). The pulmonary vascular resistance was 453 ± 78 dyne*s/cm5 after 60, 90, 120 and 150 minutes of EVLP (p = 1.0). The pulmonary artery pressure was 17.8 ± 1.0 mmHg after 60, 90, 120, and 150 minutes of EVLP (p = 1.0) and the pulmonary artery flow was 3.5 ± 0.4 l/min after 60, 90, 120, and 150 minutes of EVLP (p = 1.0). The mean weight of the pulmonary grafts after harvesting was 574 ± 20 g at the beginning of EVLP 541 ± 24 g and, after 150 min of EVLP, 668 ± 33 (p = 0.011). Conclusions: The blood gases and hemodynamic parameters in the pulmonary grafts did not improve as a result of the extra 90 minutes of EVLP. However, the weight of the pulmonary graft increased significantly with increasing duration of EVLP, indicating lung perfusion injury.

BACKGROUND: A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. A method to evaluate and recondition lungs ex vivo has been tested on donor lungs that have been rejected for transplantation. METHODS: The donor lungs were reconditioned ex vivo in an extracorporeal membrane oxygenation (ECMO) circuit with STEEN solution (Vitrolife AB, Kungsbacka, Sweden) mixed with erythrocytes. The hyperoncotic solution dehydrates edematous lung tissue. Functional evaluations were performed with deoxygenated perfusate by varying the inspired fraction of oxygen. After the reconditioning, the lungs were kept immersed at 8 degrees C in extracorporeal membrane oxygenation until transplantation was performed. RESULTS: Six of nine initially rejected donor lungs were reconditioned to acceptable function, and in six recipients, double lung transplantation was performed. Three-month survival was 100%. One patient has since died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are alive and well without any sign of bronchiolitis obliterans syndrome 24 months after the transplantation. CONCLUSIONS: The result from the present study is promising, and we continue to transplant reconditioned lungs.

The effect of acute intraoperative plateletpheresis (25% platelet yield) in combination with intraoperative low-dose aprotinin (2 million units) on blood conservation was investigated in 18 young adult patients undergoing elective Ross operation. The results were compared with a group of 19 similar patients without plateletpheresis (control group). The hematological and coagulation parameters at admission and discharge were statistically similar in both groups. The total blood product transfusion requirements were significantly reduced in the plateletpheresis group compared with the control group (3.2 units and 5.1 units, respectively, P=0.036). The total blood donor exposure was also reduced significantly in the plateletpheresis group compared with the control group (3.2 and 6.9 donors/patient, respectively, P

The pulmonary donor pool would increase substantially if lungs could be donated after cardiac death (DCD). There have been ethical and legal obstacles since administration of heparin and cooling has to be done immediately after cardiac death. This study examines whether ventilation of DCD lungs without administering heparin or cooling the lungs after cardiac death could improve graft function.Twelve donor pigs with a mean bodyweight of 70 kg were randomized into two groups. Six animals were ventilated in situ with 50% oxygen, 4 L/min, and 5 cm H2O in positive end-expiratory pressure or PEEP for 2 h after cardiac death. Six animals served as non-ventilated controls and were exposed to warm ischemia for 2 h. After 2 h, all lungs were harvested and flush perfused with Perfadex(®) solution and stored at 8°C for another 2 h. An ex vivo lung perfusion or EVLP circuit was used for evaluation.Non-ventilated lungs developed pulmonary edema, and had highly impaired blood gas levels and a significantly increased weight. The ventilated lungs demonstrated excellent blood gas levels and unchanged weight.The increase in tolerable warm ischemic time in combination with avoiding heparinization and cooling might facilitate the use of DCD lungs for transplantation.

Background The limiting factor for lung transplantation is the lack of donor organs. The usage of lungs from donation after cardiac death (DCD) would dramatically increase donor availability. In the present paper we wanted to investigate lungs exposed to 1 h of warm ischemia without heparin followed by flush-perfusion and cold storage compared to lungs harvested from heart beating donors (HBD) using standard harvesting technique. Methods Twelve Swedish domestic pigs were randomized into two groups. Six pigs (DCD group) underwent ventricular fibrillation and were then left untouched for 1 h after declaration of death. They did not receive heparin. The lungs were then harvested and flush-perfused with Perfadex® solution and the organs were stored at 8 °C for 4 h. Six pigs (HBD group) received heparin and the lungs were harvested and flush-perfused with Perfadex® solution and the organs were stored at 8 °C for 4 h. Lung function was evaluated, using ex vivo lung perfusion (EVLP), with blood gases at different oxygen levels, pulmonary vascular resistance (PVR), lung weight, and macroscopic appearance. Results At FiO2 1.0, the PaO2 in the DCD group was 51.7 ± 2.0 kPa and in the HBD group 68.6 ± 2.4 kPa (p

Background. Only a minority of the potential candidates for lung donation are considered suitable, using current evaluation methods. A new method for ex vivo evaluation, with the potential for reconditioning of marginal and nonacceptable lungs, has been developed. This is a report of the ex vivo evaluation of six donor lungs deemed nonacceptable (arterial oxygen pressure less than 40 kPa) by the Scandiatransplant, Eurotransplant, and UK transplant organizations. Methods. The lungs are perfused ex vivo with Steen solution, a lung evaluation-preservation solution, mixed with red blood cells to a hematocrit of 15%. This extracellular solution is designed to have an optimal colloid osmotic pressure so that physiologic pressure and flow can be maintained without development of pulmonary edema. An oxygenator connected to the extracorporeal circuit maintains a normal mixed venous blood gas level in the perfusate. The lungs are ventilated and evaluated through analyses of pulmonary vascular resistance, oxygenation capacity, and arterial carbon dioxide pressure minus end-tidal carbon dioxide difference. Results. The arterial oxygen pressure (inspired oxygen fraction, 1.0) increased from 27 kPa (range, 17 to 34 kPa) in situ in the organ donor at the referring hospital to 57 kPa (range, 39 to 66 kPa) during the ex vivo evaluation. The pulmonary vascular resistance varied from 3.2 to 5.7 Wood units, and the arterial carbon dioxide pressure minus end-tidal carbon dioxide difference was in the range of 1 to 2.5 kPa. Conclusions. The arterial oxygen pressure improves significantly in this model. This ex vivo evaluation model is a valuable addition to the armamentarium in finding acceptable lungs in a donor population with inferior arterial oxygen pressure values.

The aim of the present study was to compare the efficacy of intratracheal continuous insufflation of oxygen (CIO) with intermittent positive pressure ventilation (IPPV) regarding gas exchange and haemodynamics during mechanical chest compression-active decompression cardiopulmonary resuscitation (mCPR) provided by the LUCAS device. Ventricular fibrillation (VF) was induced electrically and ventilation was discontinued in 16 pigs, mean body weight 23 kg (range 22-27 kg). They were randomized into two groups (CIO versus IPPV). After 8 min of VF, mCPR was started and run for 30 min in normothermia, after which defibrillation was attempted during on-going mCPR. Return of spontaneous circulation was obtained in eight of eight CIO pigs and in four of eight IPPV pigs. Arterial oxygen tension (P < 0.05) and coronary perfusion pressure (P < 0.01) were significantly higher in the CIO pigs. Arterial CO(2)-tension was subnormal in both groups and significantly (P < 0.05) lower in the IPPV-pigs (around 4.5 versus 3.0 kPa). The intratracheal pressure differed significantly (P < 0.001) between the two groups. It was negative in each decompression phase in the IPPV pigs in spite of 6 mmHg of PEEP. The CIO pigs had a positive intratracheal pressure during the whole cycle of mCPR, with a minimum pressure of 8 mmHg during each decompression phase. To conclude, mCPR combined with CIO gave adequate ventilation and significantly better oxygenation and coronary perfusion pressure than mCPR combined with IPPV.

Outcome after prehospital defibrillation remains dire. The aim of the present study was to elucidate the pathophysiology of cardiac arrest and to suggest ways to improve outcome. Ventricular fibrillation (VF) was induced in air-ventilated pigs, after which ventilation was withdrawn. After 6.5 min of VF, ventilation with 100% oxygen was initiated. In six pigs (group I), defibrillation was the only treatment carried out. In another six pigs (group II), mechanical chest compression-decompression CPR (mCPR) was carried out for 3.5 min followed by a 40-s hands-off period before defibrillation. If unsuccessful, mCPR was resumed for a further 30 s before a second or a third, 40-s delayed, shock was given. In a final six pigs (group III) mCPR was applied for 3.5 min after which up to three shocks (if needed) were given during on-going mCPR. Return of spontaneous circulation (ROSC) occurred in none of the pigs in group I (0%), in 1 of six pigs in group II (17%) and in five of six pigs in group III (83%). During the first 3 min of VF arterial blood was transported to the venous circulation, with the consequence that the left ventricle emptied and the right ventricle became greatly distended. It took 2 min of mCPR to establish an adequate coronary perfusion pressure, which was lost when the mCPR was interrupted. During 30 s of mCPR coronary perfusion pressure was negative, but a carotid flow of about 25% of basal value was obtained. In this pig model, VF caused venous congestion, an empty left heart, and a greatly distended right heart within 3 min. Adequate heart massage before and during defibrillation greatly improved the likelihood of return of spontaneous circulation (ROSC).

Background If lungs from patients dying of heart attacks are to serve as donor organs in a safe way, their function should be properly assessed before transplantation. The aim of this study was to investigate donor lung function evaluation in a realistic large animal model. Methods Twelve 60-kg pigs were used. Five minutes after ventricular fibrillation was induced, cardiopulmonary resuscitation was initiated and maintained for 20 minutes. After a 10-min hands-off period, heparin was administered through a central venous catheter followed by 20 chest compressions. Intrapleural cooling was initiated after 65 minutes of warm ischemia. Cooling proceeded for 6 hours within the cadaver, after which lung function was assessed ex vivo. Recipient pigs underwent left lung transplantation followed by right pneumonectomy, thus making these animals 100% dependent for their survival on the function of the donor lungs. Results The assessment showed that all lungs had adequate function to serve as donor lungs. All recipient animals were in good condition during the 24-hour observation period after the operation. The blood gas function did not differ significantly from that in the healthy donor animals before induction of ventricular fibrillation; pulmonary vascular resistance was within normal range. Conclusions Lungs from non–heart-beating donors topically cooled in situ for 6 hours after 65 minutes of warm ischemia were assessed ex vivo and found to have normal function. They were then transplanted and retained normal function during a 24-hour observation period.

Summary Background In animals, we have previously done successful lung transplantations using organs from nonheart-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. Methods 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. Results 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. Interpretation 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. Lancet 2001; 357: 825–29 See Commentary page 819

To evaluate the lung function of donors after circulatory deaths (DCDs),ex vivolung perfusion (EVLP) has been shown to be a valuable method. We present modified EVLP where lung atelectasis is removed, while the lung perfusion is temporarily shut down. Twelve pigs were randomized into two groups: modified EVLP and conventional EVLP. When the lungs had reached 37°C in the EVLP circuit, lung perfusion was temporarily shut down in the modified EVLP group, and positive end-expiratory pressure (PEEP) was increased to 10 cm H2O for 10 minutes. In the conventional EVLP group, PEEP was increased to 10 cm H2O for 10 minutes with unchanged lung perfusion. In the modified EVLP group, the arterial oxygen partial pressure (PaO2) was 18.5 ± 7.0 kPa before and 64.5 ± 6.0 kPa after the maneuver (P<0.001). In the conventional EVLP group, the PaO2was 16.8 ± 3.1 kPa and 46.8 ± 2.7 kPa after the maneuver (P<0.01;P<0.01). In the modified EVLP group, the pulmonary graft weight was unchanged, while in the conventional EVLP group, the pulmonary graft weight was significantly increased. Modified EVLP with normoventilation of the lungs without ongoing lung perfusion for 10 minutes may eliminate atelectasis almost completely without harming the lungs.

OBJECTIVES: Allogeneic blood transfusion and reoperation for postoperative bleeding after the coronary artery bypass grafting have a negative impact on the patient outcome. This study aimed at evaluating the effects of reduced doses of heparin and protamine on the patient outcome, using a heparin-coated mini-cardiopulmonary bypass (CPB) system. METHODS: Sixty patients undergoing elective first-time CPB were prospectively randomized either to have a reduced systemic heparinization [activated clotting time (ACT) = 250 s] or to a control group perfused with a full heparin dose (ACT = 420 s). Blood transfusions, ventilation time, early postoperative bleeding, ICU stay, reoperations for bleeding, postoperative cognitive status and the level of mobilization were registered. RESULTS: Twenty-nine patients were randomized to the control group, 27 patients to the low-dose group and 4 patients were excluded because of protocol violations. Four patients in the control group received a total of 10 units of packed red blood cells, and in the lowdose group, no transfusions were given, P= 0.046. No patient was reoperated because of bleeding. The ICU stay was significantly shorter in the low-dose group (8.4 vs 13.7 h, P= 0.020), less dependent on oxygen on the first postoperative day (78 vs 97%, P= 0.034), better mobilized (89 vs 59%, P= 0.006) and had less pain (visual analogue scale 2.0 vs 3.5, P= 0.019) compared with the control group. CONCLUSIONS: The use of a mini-CPB system combined with a low dose of heparin reduced the need for blood transfusions and may facilitate the faster mobilization of the patients.

A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. We have recently reported the results of the first six double lung transplantations performed with donor lungs reconditionedex vivothat had been deemed unsuitable for transplantation by the Scandiatransplant, Eurotransplant, and UK Transplant organizations because the arterial oxygen pressure was less than 40 kPa. The three-month survival of patients undergoing transplant with these lungs was 100%. One patient died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are still alive and well 24 months after transplantation, with no signs of bronchiolitis obliterans syndrome. The donor lungs were reconditionedex vivoin an extracorporeal membrane oxygenation circuit using STEEN solution mixed with erythrocytes, to dehydrate edematous lung tissue. Functional evaluation was performed with deoxygenated perfusate at different inspired fractions of oxygen. The arterial oxygen pressure was significantly improved in this model. Thisex vivoevaluation model is thus a valuable addition to the armamentarium in increasing the number of acceptable lungs in a donor population with inferior arterial oxygen pressure values, thereby, increasing the lung donor pool for transplantation. In the following paper we present our clinical experience from the first six patients in the world. We also present the technique we used in detail with flowchart.

OBJECTIVE: We have compared the effectiveness, time required for de-airing, and safety of a newly developed de-airing technique for open left heart surgery (Lund technique) with a standardized carbon dioxide insufflation technique. METHODS: Twenty patients undergoing elective open aortic valve surgery were randomized prospectively to the Lund technique (Lund group, n = 10) or the carbon dioxide insufflation technique (carbon dioxide group, n = 10). Both groups were monitored intraoperatively during de-airing and for 10 minutes after weaning from cardiopulmonary bypass by transesophageal echocardiography and online transcranial Doppler for the severity and the number of gas emboli, respectively. The systemic arterial partial pressure of carbon dioxide and pH were also monitored in both groups before, during, and after cardiopulmonary bypass. RESULTS: The severity of gas emboli observed on transesophageal echocardiography and the number of microembolic signals recorded by transcranial Doppler were significantly lower in the Lund group during the de-airing procedure (P = .00634) and in the first 10 minutes after weaning from cardiopulmonary bypass (P = .000377). Furthermore, the de-airing time was significantly shorter in the Lund group (9 vs 15 minutes, P = .001). The arterial pH during the cooling phase of cardiopulmonary bypass was significantly lower in the carbon dioxide group (P = .00351), corresponding to significantly higher arterial partial pressure of carbon dioxide (P = .005196) despite significantly higher gas flows (P = .0398) in the oxygenator throughout the entire period of cardiopulmonary bypass. CONCLUSIONS: The Lund de-airing technique is safer, simpler, and more effective compared with the carbon dioxide insufflation technique. The technique is also more cost-effective because the de-airing time is shorter and no extra expenses are incurred. (Less)

Endotoxaemia is thought to occur in cardiac surgery using extracorporeal circulation (ECC) and a positive correlation has been proposed between the magnitude of endotoxaemia and risk for postoperative complications. We studied the effects of a new endotoxin adsorber device (Alteco® LPS adsorber) in patients undergoing cardiac surgery with ECC, with special reference to safety and ease of use. Fifteen patients undergoing coronary artery bypass and/or valvular surgery were studied. In 9 patients, the LPS Adsorber was included in the bypass circuit between the arterial filter and the venous reservoir. Flow through the adsorber was started when the aorta was clamped and stopped at the end of perfusion. Flow rate was kept at 150 ml/min. Six patients served as controls with no adsorber in the circuit. Samples were taken for analysis of endotoxin, TNFα, IL-1ß and IL-6 as well as complement factors C3, C4 and C1q. Whole blood coagulation status was evaluated using thromboelastograpy (TEG) and platelet count. No adverse events were encountered when the adsorber was used in the circuit. Blood flow through the device was easily monitored and kept at the desired level. Platelet count decreased in both groups during surgery. TEG data revealed a decrease in whole blood clot strength in the control group while it was preserved in the adsorber group. Endotoxin was detected in only 2 patients and IL-1ß in 4 patients. IL-6 decreased in both groups whereas no change in TNF concentrations was found. C3 fell in both groups, but no changes wer found in C4 and C1q. The Alteco® LPS adsorber can be used safely and is easy to handle in the bypass circuit. No complications related to the use of the adsorber were noted. The intended effects of the adsorber, i.e. removal of endotoxin from the blood stream could not be evaluated in this study, presumably due to the small number of patients and the relatively short perfusion times.

Purpose This article describes an ex vivo method to recondition and transplant rejected donor lungs. Description A 19-year-old man was brain dead after a traffic accident. A roentgenogram showed bilateral lung contusion. He had ongoing intratracheal bleeding. After optimizing ventilator treatment and suctioning the airways, Pao 2 was 9 kPa (67.5 mm Hg) on FiO 2 = 0.7. The lungs were rejected by all transplantation centers in the Nordic countries. We harvested the lungs for research. The right lung was severely injured. The left lung was edematous with bleeding spots in the lower lobe, and the mediobasal segment was atelectatic. The left lung was reconditioned ex vivo and kept in topical extracorporeal membrane oxygenation until it was transplanted into a 70-year-old man with chronic obstructive pulmonary disease 17 hours later. Evaluation The transplanted lung functioned very well, and the patient recovered uneventfully. At 3 months control, a computed tomographic thoracic scan and transbronchial biopsies showed a normal left lung, and the patient was in very good clinical condition, only to succumb to death from unrelated events 11 months after the transplantation. Conclusions Rejected donor lungs may be successfully transplanted after being reconditioned ex vivo .