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The medical researchers have succeeded in keeping the lungs viable for up to 24 hours, a feat no other group worldwide has achieved to date. The research is being supported by the Saarland state government.
The following text has been machine translated from the German with no human editing.
The research laboratory not only resembles an intensive care unit, it is one – for a single organ. In the middle of the room stands a table covered with blue surgical drapes, on which sits a large glass box flanked by numerous medical devices: monitoring screens display curves, cables and tubes lead from a heart-lung machine, ventilator and infusion pumps to the rear glass wall of the box. Its panes are so fogged up from the moisture inside that the pig lung in its silver shell is not immediately visible. Only after a doctoral student briefly turns off the humidification and fans away the mist inside does the lung gradually appear in the glass case. It comes from a six-month-old pig, looks surprisingly large and rises and falls rhythmically when ventilated.
"This is a living organ," emphasises Professor Sascha Kreuer, "we have to constantly humidify the lungs and keep their metabolism going." The physician is a professor at Saarland University and heads the Laboratory for Experimental Anaesthesiology at Saarland University Hospital in Homburg. Together with Professor Thomas Volk, Director of the University Clinic for Anaesthesiology, and Christian Bur, an expert in gas sensor systems, Kreuer is working to reduce animal testing for pharmaceutical and medical research and replace it with the living lung as a novel, universal, interdisciplinary test model.
The team led by Sascha Kreuer and Thomas Volk is the first research group worldwide to succeed in stabilising pig lungs, which would otherwise end up as slaughterhouse waste, for 24 hours using their innovative method – as a living organ with an intact metabolism. In individual cases, they have even managed to achieve this for longer. "We can usually manage 12 to 24 hours. Our goal is to continue optimising the processes so that we can keep the organs stable for 24 hours as standard," says Sascha Kreuer. That's a lot of time available for experiments. "The lungs consume glucose and have a metabolism. This allows us to test the effects of drugs on them under real-life conditions and measure them in the exhaled air, among other things," explains the physician.
At four o'clock in the morning, when the research team picks up the lungs from the butcher, a meticulously planned schedule begins. The researchers also meticulously record each of their steps, when which tests are carried out, when they administer which drugs or what measures they take to maintain lung function. The organ is ventilated and supplied with blood: a special device replaces the heart and pumps pig's blood, heated to exactly 37 degrees and already mixed with carbon dioxide and oxygen, through the pulmonary artery into the dense network of tiny blood vessels – before it flows back from the pulmonary vein into the pump's container.
Universal research platform
"With the lung model, we are creating a universal research platform that allows us to perform a wider range of tests than would be possible with laboratory animals," explains Clinic Director Thomas Volk, who holds the Chair of Anaesthesiology at Saarland University. Under real conditions, new active substances can be tested, for example those that are inhaled: to do this, the doctors nebulise the inhalant directly into the lungs. The organ can also be rinsed out and the composition of the fluid obtained in this way analysed. "We can also add active substances to the blood that supplies the lungs and then measure their concentration in the exhaled air without contact. This allows us to use the model to research the individual dosage of drugs, for example, and expand the possibilities for drug monitoring," says Sascha Kreuer.
Until now, drug levels have mostly been determined by blood tests, which are time-consuming, costly and produce delayed results. If the lung model could be used to investigate whether drugs are transferred into exhaled air, this would be the first step towards contact-free, rapid and simple respiratory gas analysis. "A model for lung infection is also possible. We can infect parts of the organ with pathogens and then examine exhaled air or tissue," adds Thomas Volk.
The medical researchers are collaborating with other disciplines at Saarland University. "The collaboration with the departments of clinical pharmaceutical science and medical microbiology, for example, enriches the project. We are currently expanding these collaborations to include additional working groups," says Sascha Kreuer.
Last year, the team led by Thomas Volk, Sascha Kreuer and Christian Bur was awarded the Saarland Research Prize for the Avoidance of Animal Testing for the development of the lung research platform.
Analysis of exhaled air
The analysis of exhaled air is the focus of Professor Sascha Kreuer's research. After several years of research, he succeeded in optimising the method used to measure the anaesthetic propofol in exhaled air. "Using the lung model, we were also able to show that propofol can be metabolised by the lungs. This had been suspected, but could not be proven," explains Sascha Kreuer. "We can generally measure the concentration of active substances or their degradation products in the exhaled air of our lung model. Based on this, we calculate the concentration in blood plasma and draw conclusions about the effect or an individualised dosage," explains the researcher.
The research team has been developing the entire novel procedure for the lung research platform for around three years – there was hardly any empirical data they could draw on. On the one hand, the physicians worked out the numerous individual steps required to supply the lungs. On the other hand, the team coordinated all technical devices for the procedure in its experiments – right down to the custom-made connections between the technology and the lungs and the sophisticated measurement methods for analysing the exhaled air. This is where Christian Bur comes in. The engineer has a doctoral degree and conducts research at the Chair of Measurement Technology in Saarbrücken as part of Professor Andreas Schütze's team: the engineers specialise in gas measurement technology and the associated artificial intelligence.
Gas sensor system
The sensor technology challenge in this project lies in measuring substances in very low concentrations. Exhaled air consists of a veritable cocktail of many different gaseous substances, from carbon dioxide and nitrogen to a multitude of minute traces of substances that vary from person to person and from animal to animal," explains Christian Bur, who is researching novel gas sensor systems to detect volatile organic compounds with ever greater accuracy.
The technical sensory organs developed by the Saarbrücken research team track down individual molecules among billions of air molecules: in a whole universe of particles, they detect specific individual gas particles and measure their concentration. The team normally uses this technology to monitor indoor spaces for pollutants and air purity, detect leaks or assess the quality of food. Now Christian Bur is using the sophisticated technical sensory organs to find tiny traces in the respiratory gas of the lung model. "To do this, the sensors continuously measure the concentration of certain substances, providing information about the amount exhaled over a period of time. Metal oxide-based semiconductor gas sensors are used for this purpose. We are constantly refining their signal evaluation," explains Christian Bur.
Numerous doctoral candidates and students are involved in the research, both on the medical and technical sides.
The Saarland Ministry of Science has already approved two consecutive grants for the lung research platform: as part of the state research funding programme, Saarland supported the development of the test model, and since August, the follow-up project has been funded, in which the research teams aim to automate many of the process steps.
The working groups are part of the "3R Platform Saar" project: on the initiative of Saarland University, numerous partners have joined forces on this platform with the aim of avoiding, reducing and improving animal testing (replace, reduce, refine, or "3R"). The platform systematically records alternative methods to animal testing available in Saarland, raises awareness of them and connects researchers.
Questions answered by:
Prof. Dr. med. Sascha Kreuer (Department of Anaesthesiology, Intensive Care Medicine, Emergency Medicine and Pain Therapy at Saarland University Hospital)
Tel.: +49 6841 16-26915 E-mail: sascha.kreuer(at)uks.eu
Prof. Dr. med. Thomas Volk (Chair of Anaesthesiology at Saarland University and Director of the Department of Anaesthesiology, Intensive Care and Pain Management at Saarland University Hospital)
Tel.: +49 6841 16-22485, email: thomas.volk(at)uks.eu
Dr Christian Bur (postdoctoral researcher and group leader for gas measurement technology at the Chair of Measurement Technology, Saarland University)
Tel.: 0681-302/2256, email: c.bur(at)lmt.uni-saarland.de
Press photos available for download:
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