Alpha-1-antitrypsin protects vascular grafts of brain-dead rats against ischemia/reperfusion injury
Introduction - Endothelial dysfunction is a potential side effect of brain death (BD). Ischemia/reperfusion (IR) injury during heart transplantation may lead to further endothelial damage. Protective effects of alpha-1-antitrypsin (AAT), a human neutrophil serine protease inhibitor, have been demons...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 2023
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| In: |
Journal of surgical research
Year: 2023, Volume: 283, Pages: 953-964 |
| ISSN: | 1095-8673 |
| DOI: | 10.1016/j.jss.2022.11.047 |
| Online Access: | Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jss.2022.11.047 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022480422007880 
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| Author Notes: | Qingwei Ding, MD, Sivakkanan Loganathan, MD, Pengyu Zhou, MD, Alex Ali Sayour, MD, Paige Brlecic, MD, Tamás Radovits, MD, PhD, Roxane Domain, MSc, Brice Korkmaz, PhD, Matthias Karck, MD, Gábor Szabó, MD, PhD, and Sevil Korkmaz-Icöz, PhD |
| Summary: | Introduction - Endothelial dysfunction is a potential side effect of brain death (BD). Ischemia/reperfusion (IR) injury during heart transplantation may lead to further endothelial damage. Protective effects of alpha-1-antitrypsin (AAT), a human neutrophil serine protease inhibitor, have been demonstrated against IR injury. We hypothesized that AAT protects brain-dead rats’ vascular grafts from IR injury. - Methods - Donor rats were subjected to BD by inflation of a subdural balloon. After 5.5 h, aortic rings were immediately mounted in organ baths (BD, n = 6 rats) or preserved in saline, supplemented either with vehicle (BD-IR, n = 8 rats) or AAT (BD-IR + AAT, n = 14 rats) for 24 h. During organ bath experiment, rings from both IR groups were exposed to hypochlorite to simulate warm reperfusion-associated endothelial injury. Endothelial function was measured ex vivo. Immunohistochemical staining for caspases was carried out and DNA-strand breaks were evaluated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Data are presented as median (interquartile range). - Results - AAT improved IR-induced decreased maximum endothelium-dependent vasorelaxation to acetylcholine in the BD-IR + AAT aortas compared to the BD-IR group (BD: 83 (9-28) % versus BD-IR: 49 (39-60) % versus BD-IR + AAT: 64 (24-42) %, P < 0.05). Additionally, an increase in the rings’ sensitivity to acetylcholine was noted after AAT (pD2-value: BD-IR + AAT: 7.35 (7.06-7.89) versus BD-IR: 6.96 (6.65-7.21), P < 0.05). Caspase-3, -8, -9, and -12 immunoreactivity and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells were significantly decreased by AAT. - Conclusions - AAT alleviates endothelial dysfunction, prevents increased caspase-3, -8, -9, and -12 levels, and decreases apoptotic DNA breakage due to BD and IR injury. This suggests that AAT treatment may be therapeutically beneficial to reduce IR-induced vascular damage. |
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| Item Description: | Online verfügbar: 9. Dezember 2022 Gesehen am 10.08.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1095-8673 |
| DOI: | 10.1016/j.jss.2022.11.047 |