Reperfusion of ischemic livers
There is a shortage of donor livers, and subsequently patients with liver failure are dying on the waiting lists. To be used as a donor, the donor must fulfil the brain death criteria including a total seizure of brain circulation - donation after brain death (DBD). Many potential donors on life support with irreversible brain damage do not fulfil the criteria and can only be harvested after withdraw of life support - donation after cardiac death (DCD). DCD livers are exposed to prolonged ischemia due to the withdraw of life support prior to harvesting, thus liver transplanted patients after DCD are variable, with many patients ending with a non-functioning liver and more frequently ischemic cholangiopathy. The current preservation method for organs is on ice - static cold storage (SCS) - allowing about 4 hours from harvest to implant. This time limit combined with the vast distances in Norway, and other parts in the world, make many livers unsuitable for transplantation.
Connecting the liver to an extracorporeal system allows for ex-vivo perfusion with oxygenated blood or fluid can dramatically improve the pool of livers. The purpose of our study is to increase our knowledge of the physiology, biochemistry and pathophysiology of the machine-perfused liver by harvesting porcine livers and perfusing them extracorporeally with various protocols.
The project will inflict minimal distress to the animals. The pigs will be kept in the animal department prior to the experiments. The conditions in the animal room will be controlled in terms of temperature, relative humidity and light/dark cycle. The animals will be fed standard porcine feed. All animals will be fasted overnight with free access to water prior to anesthesia. The experiment will be non - recovery.
This is a pilot study. The expected benefit of this study is to increase knowledge about machine perfusion of livers and potentially increasing the pool of donor livers. A total of 16 SPF Landrace pigs will be used.
We will adhere to the 3Rs. There are no alternatives to animal experiments to address our questions. The porcine liver anatomy and size is comparable to the human anatomy which in turn makes it clinically relevant. The data obtained from this study will be used in a power analysis (a statistical power of 0.8 and a one-sided type I error of 0.05), to reach a minimum required group size. There is a theoretical risk of losing animals due to transportation or bleeding during the instrumentation, in addition there is a risk of liver lesions (.e.g. due to migrating A. suum larvae causing lesions in the liver) which will render the liver unusable. We therefore include 8 animals per group, a total of 16 animals. We aim at 7 animals per groups to be included, 14 in total. In case of reaching 14 animals without any loss of animals, the remaining two will not be used. Standard sedation, anesthesia, and analgesia for pigs will be applied. Euthanasia will be due to induction of cardiac arrest with IV overdose of pentobarbital.
Connecting the liver to an extracorporeal system allows for ex-vivo perfusion with oxygenated blood or fluid can dramatically improve the pool of livers. The purpose of our study is to increase our knowledge of the physiology, biochemistry and pathophysiology of the machine-perfused liver by harvesting porcine livers and perfusing them extracorporeally with various protocols.
The project will inflict minimal distress to the animals. The pigs will be kept in the animal department prior to the experiments. The conditions in the animal room will be controlled in terms of temperature, relative humidity and light/dark cycle. The animals will be fed standard porcine feed. All animals will be fasted overnight with free access to water prior to anesthesia. The experiment will be non - recovery.
This is a pilot study. The expected benefit of this study is to increase knowledge about machine perfusion of livers and potentially increasing the pool of donor livers. A total of 16 SPF Landrace pigs will be used.
We will adhere to the 3Rs. There are no alternatives to animal experiments to address our questions. The porcine liver anatomy and size is comparable to the human anatomy which in turn makes it clinically relevant. The data obtained from this study will be used in a power analysis (a statistical power of 0.8 and a one-sided type I error of 0.05), to reach a minimum required group size. There is a theoretical risk of losing animals due to transportation or bleeding during the instrumentation, in addition there is a risk of liver lesions (.e.g. due to migrating A. suum larvae causing lesions in the liver) which will render the liver unusable. We therefore include 8 animals per group, a total of 16 animals. We aim at 7 animals per groups to be included, 14 in total. In case of reaching 14 animals without any loss of animals, the remaining two will not be used. Standard sedation, anesthesia, and analgesia for pigs will be applied. Euthanasia will be due to induction of cardiac arrest with IV overdose of pentobarbital.