Establishment and assessment of pancreas preservation using oxygenated hypothermic machine perfusion
<p><strong>Background:</strong> Pancreatic transplantation is the treatment of choice for a selected group of patients with the most severe complications of diabetes. The two main causes of early failure in this transplant are pancreatitis and venous graft thrombosis. Due to its an...
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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2022
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| _version_ | 1797106535495630848 |
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| author | Hakim, G |
| author2 | Friend, P |
| author_facet | Friend, P Hakim, G |
| author_sort | Hakim, G |
| collection | OXFORD |
| description | <p><strong>Background:</strong> Pancreatic transplantation is the treatment of choice for a selected group of patients with the most severe complications of diabetes. The two main causes of early failure in this transplant are pancreatitis and venous graft thrombosis. Due to its anatomy and physiology, the pancreas is an organ that is particularly sensitive to ischaemia reperfusion injury. The current standard technique for preserving transplants after removal and before transplantation remains static cold storage (SCS). Changes in donor characteristics (older, with more co-morbidities) have led transplant teams to consider for transplant increasingly high-risk pancreases, which are even more susceptible to ischaemia reperfusion injury.</p>
<p><strong>Aim:</strong> The objective of this study was to establish the modalities of an innovative technique for the preservation of pancreatic transplants on a pulsatile hypothermic perfusion machine (HMP) and to compare SCS, HMP and Hypothermic Oxygenated Pulsatile Perfusion (HMPO2) preservation methods for pancreas in a Donation after Circulatory Death (DCD) porcine model.</p>
<p><strong>Methods:</strong> Pancreases were retrieved after cold preservation solution flush from Sus scrofa domesticus pigs sourced at an abattoir, in a DCD model. Pancreases were cold preserved with Static Cold Storage (n=5), Hypothermic Machine Perfusion (Waves machine) (n=4), or with Hypothermic Oxygenated Pulsatile Perfusion (n=4) (medical air 300ml/min). General injury markers (lactate; lactate dehydrogenase) and exocrine markers (amylase, lipase) were assessed in the perfusate (or preservation solution for SCS) during preservation. Pancreatic resistance index, pressure and flow were also analysed. Biopsies were collected to assess pancreas oedema (wet to dry weight ratios before and after preservation).</p>
<p><strong>Results:</strong> SCS resulted in an oedema scale assessment score of 0 when compared with both HMP groups (score 1), however wet-to-dry weight ratio percentage difference was highest for SCS indicating the presence of oedema. Flow and resistance index were shown to be reciprocal, with the highest flow being achieved in the HMPO2 group. No statistically significant difference was found between HMPO2 and HMP groups for oxygen pressure in the perfusate over time. LDH levels were significantly higher in the SCS group, as well as lactate levels. Amylase and lipase levels were found to be significantly greater in the HMPO2 group. Glucose levels were highest in the HMPO2 group, whilst pH was greatest in the SCS group despite being stable across all three groups HMP, HMPO2 and SCS.</p>
<p><strong>Conclusions:</strong> HMPO2 appears to be a promising alternative method to SCS preservation, despite research in the pancreas proving more challenging than in other organs. The flow was higher in the HMPO2 group, while the degree of oedema appeared to be lower alongside lower levels of general tissue injury markers, making HMPO2 a potentially suitable alternative to preservation by static cold storage.</p> |
| first_indexed | 2024-03-07T07:03:51Z |
| format | Thesis |
| id | oxford-uuid:d9f436d3-759f-432e-a450-bdda92943dd7 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:03:51Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | oxford-uuid:d9f436d3-759f-432e-a450-bdda92943dd72022-04-05T07:30:14ZEstablishment and assessment of pancreas preservation using oxygenated hypothermic machine perfusionThesishttp://purl.org/coar/resource_type/c_bdccuuid:d9f436d3-759f-432e-a450-bdda92943dd7DiabetesPancreas TransplantationPerfusion (Physiology)EnglishHyrax Deposit2022Hakim, GFriend, PBranchereau, J<p><strong>Background:</strong> Pancreatic transplantation is the treatment of choice for a selected group of patients with the most severe complications of diabetes. The two main causes of early failure in this transplant are pancreatitis and venous graft thrombosis. Due to its anatomy and physiology, the pancreas is an organ that is particularly sensitive to ischaemia reperfusion injury. The current standard technique for preserving transplants after removal and before transplantation remains static cold storage (SCS). Changes in donor characteristics (older, with more co-morbidities) have led transplant teams to consider for transplant increasingly high-risk pancreases, which are even more susceptible to ischaemia reperfusion injury.</p> <p><strong>Aim:</strong> The objective of this study was to establish the modalities of an innovative technique for the preservation of pancreatic transplants on a pulsatile hypothermic perfusion machine (HMP) and to compare SCS, HMP and Hypothermic Oxygenated Pulsatile Perfusion (HMPO2) preservation methods for pancreas in a Donation after Circulatory Death (DCD) porcine model.</p> <p><strong>Methods:</strong> Pancreases were retrieved after cold preservation solution flush from Sus scrofa domesticus pigs sourced at an abattoir, in a DCD model. Pancreases were cold preserved with Static Cold Storage (n=5), Hypothermic Machine Perfusion (Waves machine) (n=4), or with Hypothermic Oxygenated Pulsatile Perfusion (n=4) (medical air 300ml/min). General injury markers (lactate; lactate dehydrogenase) and exocrine markers (amylase, lipase) were assessed in the perfusate (or preservation solution for SCS) during preservation. Pancreatic resistance index, pressure and flow were also analysed. Biopsies were collected to assess pancreas oedema (wet to dry weight ratios before and after preservation).</p> <p><strong>Results:</strong> SCS resulted in an oedema scale assessment score of 0 when compared with both HMP groups (score 1), however wet-to-dry weight ratio percentage difference was highest for SCS indicating the presence of oedema. Flow and resistance index were shown to be reciprocal, with the highest flow being achieved in the HMPO2 group. No statistically significant difference was found between HMPO2 and HMP groups for oxygen pressure in the perfusate over time. LDH levels were significantly higher in the SCS group, as well as lactate levels. Amylase and lipase levels were found to be significantly greater in the HMPO2 group. Glucose levels were highest in the HMPO2 group, whilst pH was greatest in the SCS group despite being stable across all three groups HMP, HMPO2 and SCS.</p> <p><strong>Conclusions:</strong> HMPO2 appears to be a promising alternative method to SCS preservation, despite research in the pancreas proving more challenging than in other organs. The flow was higher in the HMPO2 group, while the degree of oedema appeared to be lower alongside lower levels of general tissue injury markers, making HMPO2 a potentially suitable alternative to preservation by static cold storage.</p> |
| spellingShingle | Diabetes Pancreas Transplantation Perfusion (Physiology) Hakim, G Establishment and assessment of pancreas preservation using oxygenated hypothermic machine perfusion |
| title | Establishment and assessment of pancreas preservation using oxygenated hypothermic machine perfusion |
| title_full | Establishment and assessment of pancreas preservation using oxygenated hypothermic machine perfusion |
| title_fullStr | Establishment and assessment of pancreas preservation using oxygenated hypothermic machine perfusion |
| title_full_unstemmed | Establishment and assessment of pancreas preservation using oxygenated hypothermic machine perfusion |
| title_short | Establishment and assessment of pancreas preservation using oxygenated hypothermic machine perfusion |
| title_sort | establishment and assessment of pancreas preservation using oxygenated hypothermic machine perfusion |
| topic | Diabetes Pancreas Transplantation Perfusion (Physiology) |
| work_keys_str_mv | AT hakimg establishmentandassessmentofpancreaspreservationusingoxygenatedhypothermicmachineperfusion |