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Activation and modulation of cardiac poly-adenosine diphosphate ribose polymerase activity in a rat model of brain death

Lookup NU author(s): Dr John Brain, Dr Anthony RostronORCiD, Professor John Dark, Emeritus Professor John Kirby

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Abstract

DNA damage during transplantation can activate poly-adenosine diphosphate ribose polymerase (PARP) resulting in the generation of polymers of adenosine diphosphate-ribose (PAR). Excessive linkage of PAR to nuclear proteins can induce cell death, thereby limiting the function of transplanted organs. This study uses a rat model of brain death to determine the profile of PARP activation and whether mechanisms that lead to cell death can be ameliorated by appropriate donor resuscitation. The expression of PAR-linked nuclear proteins within cardiac myocytes was greatly increased after the induction of donor brain death. Importantly, infusion of noradrenaline or vasopressin to normalize the chronic hypotension produced by brain death reduced the expression of PAR to a level below baseline. These data suggest that chronic hypotension after donor brain death has the potential to limit cardiac function through the activation of PARP; however, this early cause of graft damage can be mitigated by appropriate donor resuscitation. © 2008 Lippincott Williams & Wilkins, Inc.

Publication metadata

Author(s): Brain JG, Rostron AJ, Dark JH, Kirby JA

Publication type: Article

Publication status: Published

Journal: Transplantation

Year: 2008

Volume: 85

Issue: 9

Pages: 1348-1350

ISSN (print): 0041-1337

ISSN (electronic): 1534-6080

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/TP.0b013e31816c7cec

DOI: 10.1097/TP.0b013e31816c7cec

PubMed id: 18475194

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