Dataset Information

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

ABSTRACT: 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.We developed a novel mouse model of BD and investigated the role of complement in BD-induced myocardial inflammation and injury.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.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.

SUBMITTER: Atkinson C

PROVIDER: S-EPMC2783176 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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

Atkinson Carl C Varela Juan C JC Tomlinson Stephen S

Circulation research 20091008 11

<h4>Rationale</h4>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.<h4>Objective</h4>We developed a novel mouse model of BD and investigated the role of complement in BD-induced myocardial inflammation and injury.<h4>Methods and results</h4>BD was induced by inflat ...[more]

PMID: 19815824

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Project description:Background and objectives: Organ shortage is considered to be a major limitation for increasing transplantation rates. Brain-dead donors (DBDs) are an important source of organs, but up to 50% of potential DBDs might not be identified. An active brain-dead donor search could potentially increase a deceased donor pool. The aim of this study was to evaluate the effectiveness of an active potential DBD identification program and to evaluate one year impact on the potential organ donor pool in Lithuania's biggest medical institution. Materials and Methods: An organ donor coordinator service was established and active DBD search strategy was implemented in the hospital of LSMU Kauno Klinikos, and retrospective data analysis was performed between December 2016 and December 2017. Collected data was compared to the available data of the previous year in the same center and to the donation dynamics of the whole country. Results: A total of 6734 patients were treated in all intensive care units (ICU), and 234 (3.5%) of them were identified as possible donors. No increase in potential donor's number was observed in study year (n = 34) compared to remote year (n = 37). No significant difference in potential donor's demographic data, cause of death, family refusals and medical contraindication rates. Cerebral angiography (CA) repeated in 20% of potential donors in order to confirm brain death diagnosis. More potential donors for whom CA was repeated had decompressive craniectomy done (66.7% vs. 33.3%, p = 0.018). Decompressive craniectomy statistically significantly increases the rate of repeated CA (OR 12.7; 95% CI, 1.42-113.37; p = 0.023). Active search strategy increased length of hospital stay of potential donors comparing to previous year (3.97 ± 4.73 vs. 2.51 ± 2.63, p = 0.003). An optimal time of the first four days of hospitalization to identify a potential donor was observed during our study (OR 10.42; 95% CI, 4.29-25.34; p = 0.001). Conclusions: We were not able to demonstrate active donor identification strategy superiority over the passive strategy during a short one year period; nevertheless, valuable knowledge was gained in brain death diagnostics, new terminology was implemented, and the stability of actual donor numbers was observed in the experimental donor center in the light of decreasing national results. Long-term strategy is required to achieve sustainable results in organ donation.

Dataset Information

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

Publications

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

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