How to Recondition Ex Vivo Initially Rejected Donor Lungs for Clinical Transplantation: Clinical Experience from Lund University Hospital

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 reconditioned ex vivo that 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 reconditioned ex vivo in 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. This ex vivo evaluation 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

How to Recondition Ex Vivo Initially Rejected Donor Lungs for Clinical Transplantation: Clinical Experience from Lund University Hospital

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 reconditioned ex vivo that 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 reconditioned ex vivo in 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. This ex vivo evaluation 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

Cardiorespiratory effects of venous lipid micro embolization in an experimental model of mediastinal shed blood reinfusion

<p>Abstract</p> <p>Background</p> <p>Retransfusion of the patient's own blood during surgery is used to reduce the need for allogenic blood transfusion. It has however been found that this blood contains lipid particles, which form emboli in different organs if the blood is retransfused on the arterial side. In this study, we tested whether retransfusion of blood containing lipid micro-particles on the venous side in a porcine model will give hemodynamic effects.</p> <p>Methods</p> <p>Seven adult pigs were used. A shed blood surrogate containing 400 ml diluted blood and 5 ml radioactive triolein was produced to generate a lipid embolic load. The shed blood surrogate was rapidly (<2 minutes) retransfused from a transfusion bag to the right atrium under general anesthesia. The animals' arterial, pulmonary, right and left atrial pressure were monitored, together with cardiac output and deadspace. At the end of the experiment, an increase in cardiac output and pulmonary pressure was pharmacologically induced to try to flush out lipid particles from the lungs.</p> <p>Results</p> <p>A more than 30-fold increase in pulmonary vascular resistance was observed, with subsequent increase in pulmonary artery pressure, and decrease in cardiac output and arterial pressure. This response was transient, but was followed by a smaller, persistent increase in pulmonary vascular resistance. Only a small portion of the infused triolein passed the lungs, and only a small fraction could be recirculated by increasing cardiac output and pulmonary pressure.</p> <p>Conclusion</p> <p>Infusion of blood containing lipid micro-emboli on the venous side leads to acute, severe hemodynamic responses that can be life threatening. Lipid particles will be trapped in the lungs, leading to persistent effects on the pulmonary vascular resistance.</p

Lipid Micro Emboli in Cardiac Surgery

This thesis is based on five studies. It includes the characterization of lipid micro emboli in shed mediastinal blood during cardiac surgery. The reuse of blood directly by cardiotomy suction is a common practice in order to reduce the need of blood transfusions. In shed mediastinal blood we showed that there is an abundance of lipid particles in the size range of 10-60μm. These lipid particles are also recirculated by the cardiotomy suction, through filters and the plastic tubing in the cardiopulmonary bypass (CPB) circuit. The lipid particles are quite probably in an emulsified state which renders them hydrophilic and less prone to stick to the plastic surfaces of tubing and filters. With a series of samples from the mediastinal blood and from the arterial circulation we found that the lipid particles are formed during the operation. Probable sites of origin are the bone marrow after sternotomy and the mediastinal fat tissue manipulated during the surgery in order to expose the heart for cannulation. When the blood was collected in a separate transfusion bag and transfused over a short period of time the increase of lipid micro emboli could be detected in the arterial circulation of the CPB circuit. This was measured by using a Coulter counter to analyze and count emboli in a series of blood samples. The Coulter counter was shown in the first study to be a valuable technique to evaluate embolic loads of lipid micro emboli in blood. The lungs act as physiological filters for the circulation. Embolic material is filtered effectively by the lungs. Using this filtering property of the lungs could therefore be an option in retransfusing the lipid laden mediastinal blood gathered during cardiac surgery. Using a pig model and a shed blood phantom laden with radioactive triolein as embolic material, we registered the hemodynamic results of this during CPB. Furthermore we registered the embolic load in the circulation by measuring beta radioactivity in a series of blood samples. We found that the lungs do act to trap a great deal of these lipid particles but these are then to a certain extent recirculated again. This was especially evident when the cardiac output and pressure were increased by a bolus of volume and vasoconstrictors Lipid emboli find their way into the circulation during cardiac surgery, where they can be detected and counted by the Coulter counter. When simultaneously registering micro embolic signals from a transcranial Doppler and counting lipid micro emboli in blood samples taken from the arterial line, we found a strong correlation between the two phenomena. Lipid material was also tagged by beta radioactivity and found to end up in different organs. By comparing two shed blood phantoms, one with nonemulsified lipids and the other with emulsified lipids we found that the lipid embolic matter increases in the circulation and is more easily deposited in the tissue. The overall purpose was to show that lipid micro emboli are released into the shed mediastinal blood during cardiac surgery. When this blood is retransfused, it is the source of a bombardment of lipid micro emboli in the circulation. These emboli are lodged in various organs. Lipid emboli in the emulsified state are more likely to pass into the circulation during retransfusion of shed mediastinal blood. These emboli can be detected by a transcranial Doppler in the arterial circulation of patients undergoing cardiac surgery

79. Heart transplantation in a patient with eosinophilic granulomatosis with polyangitis (Churg–Strauss syndrome)

Churg–Strauss syndrome, recently renamed eosinophilic granulomatosis with polyangitis (EGPA), was first described in 1951. It is characterized by blood and tissue eosinophilia and disseminated necrotizing vasculitis in asthmatic patients (1). Heart involvement is the leading cause of death in most of these patients which occurs in approximately 8–20% of EGPA patients and is more frequent in ANCA −-ve patients (2). Case: We report a 32 years old man with Churg–Strauss syndrome. He presented with a history of bronchial asthma and corticosteroid treatment. The patient developed severe heart failure necessitating heart transplantation in May 2014. His post operative course was uneventful except for tricuspid regurgitation which subsided during the first two months follow-up. Up till now, the patient has had 5 endomyocardial biopsies with no evidence of acute rejection (grade 0) or recurrence of EGPA. Conclusion: Only 9 patients with EGPA (Churg–Strauss syndrome) who received heart transplantation have been reported in a retrospective international multicentre study (3). To our knowledge this is the 10th case of heart transplantation in a patient with EGPA (Churg–Strauss syndrome)

Circulating particles during cardiac surgery.

Shed blood is known to be a source of lipid micro-emboli in cardiac surgery. The aim of this study was to characterize the occurrence of these particles at different stages of the operation, and to study their occurrence in the circulation at multiple time-points after the retransfusion of shed blood. 44 patients undergoing routine surgery with cardiopulmonary bypass were included. Blood was sampled from the surgical field at different sampling locations during the operation. Shed blood was collected in a transfusion bag and retransfused. After which, blood was sampled from the arterial line of the heart-lung machine. A Coulter counter was used for particle determinion. The mean volume of shed blood collected was 340+/-215 ml. Particles in the size range 10-60 microm were found at varying concentrations, with the highest concentrations being found in blood collected after cannulation and from the pleura. After retransfusion of this blood, a biphasic response was seen in the blood drawn from the efferent line of the heart-lung machine. Particles are found in shed blood at all times during cardiac surgery, and when this blood was retransfused an increase was seen in particle concentration in the heart-lung machine. Keywords: Particles; Lipid particles; Circulation; Shed mediastinal blood

Characterization of lipid particles in shed mediastinal blood.

BACKGROUND: Shed mediastinal blood is known to be a source of microemboli in cardiac surgery. The aim of this study was to characterize in detail the lipid particles found in this blood. METHODS: Blood samples were collected from 24 patients undergoing routine cardiac surgery with cardiopulmonary bypass. Arterial and shed blood was analyzed using the Coulter counter technique to establish the number and size of particles. The composition of these lipid particles was compared with that of adipose tissue from the mediastinum using gas chromatography. Scanning electron microscopy was used to visualize the lipid particles in samples of shed blood. RESULTS: Lipid particles in the size range of 10 to 60 microm were characterized in shed mediastinal blood, and more than 300,000 particles per milliliter of blood were found. Triglyceride profiles in these lipid particles and in adipose tissue were similar, suggesting that their origin is the mediastinum. Scanning electron microscopy showed spherical formations corresponding in size to the particles counted using the Coulter counter. CONCLUSIONS: During the past decade attention has focused on microembolism in cardiac surgery, and this study has helped define the problem. Different strategies, such as eliminating the use of shed mediastinal blood or purifying the blood by different techniques, may improve the results of cardiac surgery in the future

The reversible oral P2Y(12) antagonist AZD6140 inhibits ADP-induced contractions in murine and human vasculature.

OBJECTIVES: The platelet ADP P2Y(12) receptor which is a target for the antithrombotic drug clopidogrel is also distributed on vascular smooth muscle cells and stimulate contraction. This study investigates whether AZD6140, in contrast to clopidogrel, can inhibit ADP-mediated arterial contractions. METHODS: Mice were treated with clopidogrel, 50 mg/kg, 24 and 2 h before experiment. Thoracic aorta ring segments from both clopidogrel-treated (n=5) and untreated (n=4) mice were mounted in myograph baths. Contractions of human left internal mammary arteries (IMA) and small arteries were studied in an identical manner. RESULTS: Clopidogrel treatment per os did not inhibit contractions by the stable ADP analogue 2-MeSADP (10 microM). However, addition of 1 microM AZD6140 in vitro inhibited ADP contraction (% of maximal contraction by 60 mM K(+)) both in the clopidogrel-treated, from 64% to 32% (P=0.002) and in the untreated group, from 59% to 33% (P=0.015). 2-MeSADP contractions in human IMA and small arteries were inhibited by AZD6140. CONCLUSIONS: The antiplatelet drug AZD6140 blocks the contractile effects of ADP in both murine and human vasculature. These effects of AZD6140 could be beneficial in the management of conditions in which vasospasm may play a role