Donor Brain Death Exacerbates Complement-Dependent Ischemia/Reperfusion Injury in Transplanted Hearts

被引：63

作者：

Atkinson, Carl ^{[1
]}

Floerchinger, Bernhard ^{[2
,3
,4
]}

Qiao, Fei ^{[1
]}

Casey, Sarah ^{[1
]}

Williamson, Tucker ^{[1
]}

Moseley, Ellen ^{[5
]}

Stoica, Serban ^{[5
,6
,7
]}

Goddard, Martin ^{[5
]}

Ge, Xupeng ^{[8
]}

Tullius, Stefan G. ^{[2
,3
]}

Tomlinson, Stephen ^{[1
,9
]}

机构：

[1] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Transplant Surg, Boston, MA 02115 USA

[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Transplant Surg Res Lab, Boston, MA 02115 USA

[4] Univ Med Ctr Regensburg, Dept Cardiothorac Surg, Regensburg, Germany

[5] Papworth Hosp NHS Trust, Dept Pathol, Cambridge, England

[6] Bristol Childrens Hosp, Bristol, Avon, England

[7] Inst Heart, Bristol, Avon, England

[8] Univ Calif Los Angeles, Los Angeles, CA 90024 USA

[9] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA

来源：

CIRCULATION | 2013年 / 127卷 / 12期

基金：

美国国家卫生研究院;

关键词：

inflammation; ischemia; reperfusion injury; transplantation; ISCHEMIA-REPERFUSION INJURY; P-SELECTIN LIGAND; LIVER-REGENERATION; ACTIVATION; RAT; C3A; ALLOGRAFT; C5A; MEDIATORS; KIDNEY;

D O I：

10.1161/CIRCULATIONAHA.112.000784

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.)

引用

页码：1290 / +

页数：12

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