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Complement-dependent inflammation and injury in a murine model of brain dead donor hearts.

Authors :
Atkinson C
Varela JC
Tomlinson S
Source :
Circulation research [Circ Res] 2009 Nov 20; Vol. 105 (11), pp. 1094-101. Date of Electronic Publication: 2009 Oct 08.
Publication Year :
2009

Abstract

Rationale: Donor brain death (BD) is an unavoidable occurrence in heart transplantation and results in profound physiological derangements that render the heart more susceptible to ischemia/reperfusion injury in the recipient and likely has negative long-term consequences to allograft survival.<br />Objective: We developed a novel mouse model of BD and investigated the role of complement in BD-induced myocardial inflammation and injury.<br />Methods and Results: BD was induced by inflation of a balloon catheter in the cranial cavity. BD in wild-type mice resulted in a significant increase in serum concentrations of the complement activation product complement component (C)3a, and immunohistochemical analysis of heart sections demonstrated C3 deposition on the vascular endothelium and surrounding myocytes. Following induction of BD in complement (C3)-deficient mice, cardiac troponin levels, and histological evidence of injury were significantly reduced compared to wild-type mice. C3 deficiency was also associated with reduced myocardial leukocyte infiltration and reduced or absent expression of P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor-alpha, and interleukin-1beta.<br />Conclusions: These data indicate an important role for complement in BD-induced inflammation and injury and suggest that a complement inhibitory strategy applied to the donor (in addition to the recipient) may provide graft protection.

Details

Language :
English
ISSN :
1524-4571
Volume :
105
Issue :
11
Database :
MEDLINE
Journal :
Circulation research
Publication Type :
Academic Journal
Accession number :
19815824
Full Text :
https://doi.org/10.1161/CIRCRESAHA.109.194977