Activation and modulation of cardiac poly-adenosine diphosphate ribose polymerase activity in a rat model of brain death.
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.
Brain
John G
JG
Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, The Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, United Kingdom. j.g.brain@ncl.ac.uk
Rostron
Anthony J
AJ
Dark
John H
JH
Kirby
John A
JA
D000818:Animals; D001925:Brain Damage, Chronic / Q000209:etiology; D001926:Brain Death / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology; D004249:DNA Damage; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D032383:Myocytes, Cardiac / Q000201:enzymology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D014180:Transplantation / Q000009:adverse effects
D011065:Poly(ADP-ribose) Polymerases