| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Circulation | ||||
| Publisher: | LIPPINCOTT WILLIAMS & WILKINS | ||||
| Place of Publication: | PHILADELPHIA | ||||
| Volume: | 127 | ||||
| Number of Issue or Book Chapter: | 12 | ||||
| Page Range: | pp. 1290-1299 | ||||
| Date: | 2013 | ||||
| Institutions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie | ||||
| Identification Number: |
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| Keywords: | ISCHEMIA-REPERFUSION INJURY; P-SELECTIN LIGAND; LIVER-REGENERATION; ACTIVATION; RAT; C3A; ALLOGRAFT; C5A; MEDIATORS; KIDNEY; inflammation; ischemia; reperfusion injury; transplantation | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 62727 |
Web of ScienceAbstract
Background-Brain death (BD) can immunologically prime the donor organ and is thought to lead to exacerbated ischemia/reperfusion injury after transplantation. Using a newly developed mouse model of BD, we investigated the effect of donor BD on posttransplantation cardiac ischemia/reperfusion injury. We further investigated the therapeutic effect of a targeted complement inhibitor in recipients of ...
Abstract
Background-Brain death (BD) can immunologically prime the donor organ and is thought to lead to exacerbated ischemia/reperfusion injury after transplantation. Using a newly developed mouse model of BD, we investigated the effect of donor BD on posttransplantation cardiac ischemia/reperfusion injury. We further investigated the therapeutic effect of a targeted complement inhibitor in recipients of BD donor hearts and addressed the clinical relevance of these studies by analyzing human heart biopsies from BD and domino (living) donors. Methods and Results-Hearts from living or BD donor C57BL/6 mice were transplanted into C57BL/6 or BALB/c recipients. Recipient mice were treated with the complement inhibitor CR2-Crry or vehicle control (n=6). Isografts were analyzed 48 hours after transplantation for injury, inflammation, and complement deposition, and allografts were monitored for graft survival. Human cardiac biopsies were analyzed for complement deposition and inflammatory cell infiltration. In the murine model, donor BD exacerbated ischemia/reperfusion injury and graft rejection, as demonstrated by increased myocardial injury, serum cardiac troponin, cellular infiltration, complement deposition, inflammatory chemokine and cytokine levels, and by decreased graft survival. CR2-Crry treatment of recipients significantly reduced all measured outcomes in grafts from both BD and living donors compared with controls. Analysis of human samples documented the relevance of our experimental findings and revealed exacerbated complement deposition and inflammation in grafts from BD donors compared with grafts from living donors. Conclusions-BD exacerbates posttransplantation cardiac ischemia/reperfusion injury in mice and humans and decreases survival of mouse allografts. Furthermore, targeted complement inhibition in recipient mice ameliorates BD-exacerbated ischemia/reperfusion injury. (Circulation. 2013; 127: 1290-1299.)
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