Cyclosporine A Does Not Mitigate Liver Ischemia/Reperfusion Injury in an Ex Vivo Porcine Model of Donation After Circulatory Death Article Swipe
Joshua Hefler
,
Sanaz Hatami
,
Aducio Thiesen
,
Mitchell J. Wagner
,
Guilherme Mainardi Aguiar da Silva
,
Sayed Himmat
,
Constantine Karvellas
,
David L. Bigam
,
Darren H. Freed
,
A. M. James Shapiro
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.12659/aot.941054
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.12659/aot.941054
BACKGROUND Ischemia/reperfusion injury (IRI) is an inherent problem in organ transplantation, owing to the obligate period of ischemia that organs must endure. Cyclosporine A (CsA), though better know as an immunosuppressant, has been shown to mitigate warm IRI in a variety of organ types, including the liver. However, there is little evidence for CsA in preventing hepatic IRI in the transplant setting. MATERIAL AND METHODS In the present study, we tested the effect of CsA on hepatic IRI in a large-animal ex vivo model of donation after circulatory death (DCD). Porcine donors were pre-treated with either normal saline control or 20 mg/kg of CsA. Animals were subject to either 45 or 60 minutes of warm ischemia before hepatectomy, followed by 2 or 4 hours of cold storage prior to reperfusion on an ex vivo circuit. Over the course of a 12-hour perfusion, perfusion parameters were recorded and perfusate samples and biopsies were taken at regular intervals. RESULTS Peak perfusate lactate dehydrogenase was significantly decreased in the lower-ischemia group treated with CsA compared to the untreated group (4220 U/L [3515-5815] vs 11 305 [10 100-11 674]; P=0.023). However, no difference was seen between controls and CsA-treated groups on other parameters in perfusate alanine or asparagine aminotransferase (P=0.912, 0.455, respectively). Correspondingly, we found no difference on midpoint histological injury score (P=0.271). CONCLUSIONS We found minimal evidence that CsA is protective against hepatic IRI in our DCD model.
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Concepts
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.12659/aot.941054
- https://annalsoftransplantation.com/download/index/idArt/941054
- OA Status
- hybrid
- Cited By
- 1
- References
- 29
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4390536086
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4390536086Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.12659/aot.941054Digital Object Identifier
- Title
-
Cyclosporine A Does Not Mitigate Liver Ischemia/Reperfusion Injury in an Ex Vivo Porcine Model of Donation After Circulatory DeathWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-12-27Full publication date if available
- Authors
-
Joshua Hefler, Sanaz Hatami, Aducio Thiesen, Mitchell J. Wagner, Guilherme Mainardi Aguiar da Silva, Sayed Himmat, Constantine Karvellas, David L. Bigam, Darren H. Freed, A. M. James ShapiroList of authors in order
- Landing page
-
https://doi.org/10.12659/aot.941054Publisher landing page
- PDF URL
-
https://annalsoftransplantation.com/download/index/idArt/941054Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://annalsoftransplantation.com/download/index/idArt/941054Direct OA link when available
- Concepts
-
Ex vivo, Medicine, Reperfusion injury, Ischemia, Liver transplantation, Perfusion, Transplantation, Machine perfusion, Lactate dehydrogenase, In vivo, Anesthesia, Cold storage, Surgery, Internal medicine, Biology, Biochemistry, Enzyme, Horticulture, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1Per-year citation counts (last 5 years)
- References (count)
-
29Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.endure. | 21 |
| abstract_inverted_index.hepatic | 56, 76, 229 |
| abstract_inverted_index.lactate | 159 |
| abstract_inverted_index.minimal | 222 |
| abstract_inverted_index.minutes | 112 |
| abstract_inverted_index.present | 67 |
| abstract_inverted_index.problem | 7 |
| abstract_inverted_index.regular | 154 |
| abstract_inverted_index.samples | 148 |
| abstract_inverted_index.storage | 126 |
| abstract_inverted_index.subject | 106 |
| abstract_inverted_index.treated | 168 |
| abstract_inverted_index.variety | 40 |
| abstract_inverted_index.However, | 47, 186 |
| abstract_inverted_index.MATERIAL | 62 |
| abstract_inverted_index.biopsies | 150 |
| abstract_inverted_index.circuit. | 134 |
| abstract_inverted_index.compared | 171 |
| abstract_inverted_index.controls | 192 |
| abstract_inverted_index.donation | 85 |
| abstract_inverted_index.evidence | 51, 223 |
| abstract_inverted_index.followed | 118 |
| abstract_inverted_index.inherent | 6 |
| abstract_inverted_index.ischemia | 17, 115 |
| abstract_inverted_index.midpoint | 214 |
| abstract_inverted_index.mitigate | 35 |
| abstract_inverted_index.obligate | 14 |
| abstract_inverted_index.recorded | 145 |
| abstract_inverted_index.setting. | 61 |
| abstract_inverted_index.(P=0.912, | 205 |
| abstract_inverted_index.P=0.023). | 185 |
| abstract_inverted_index.decreased | 163 |
| abstract_inverted_index.including | 44 |
| abstract_inverted_index.perfusate | 147, 158, 200 |
| abstract_inverted_index.perfusion | 142 |
| abstract_inverted_index.untreated | 174 |
| abstract_inverted_index.(P=0.271). | 218 |
| abstract_inverted_index.BACKGROUND | 0 |
| abstract_inverted_index.asparagine | 203 |
| abstract_inverted_index.difference | 188, 212 |
| abstract_inverted_index.intervals. | 155 |
| abstract_inverted_index.parameters | 143, 198 |
| abstract_inverted_index.perfusion, | 141 |
| abstract_inverted_index.preventing | 55 |
| abstract_inverted_index.protective | 227 |
| abstract_inverted_index.transplant | 60 |
| abstract_inverted_index.CONCLUSIONS | 219 |
| abstract_inverted_index.CsA-treated | 194 |
| abstract_inverted_index.[3515-5815] | 178 |
| abstract_inverted_index.circulatory | 87 |
| abstract_inverted_index.pre-treated | 93 |
| abstract_inverted_index.reperfusion | 129 |
| abstract_inverted_index.Cyclosporine | 22 |
| abstract_inverted_index.hepatectomy, | 117 |
| abstract_inverted_index.histological | 215 |
| abstract_inverted_index.large-animal | 80 |
| abstract_inverted_index.dehydrogenase | 160 |
| abstract_inverted_index.significantly | 162 |
| abstract_inverted_index.lower-ischemia | 166 |
| abstract_inverted_index.respectively). | 207 |
| abstract_inverted_index.Correspondingly, | 208 |
| abstract_inverted_index.aminotransferase | 204 |
| abstract_inverted_index.transplantation, | 10 |
| abstract_inverted_index.immunosuppressant, | 30 |
| abstract_inverted_index.Ischemia/reperfusion | 1 |
| cited_by_percentile_year.max | 95 |
| cited_by_percentile_year.min | 91 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 10 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.6200000047683716 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.68127827 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |