title: Heat shock protein, inducible nitric oxide synthase and apoptotic markers in the acute phase of human cardiac transplantation.
abstract: OBJECTIVE
  Solid organ transplantation is associated with activation of apoptotic pathways and other stress markers. We aimed to describe the expression of Bax, Bcl-2, iNOs and Hsp-70 in the endothelium and myocytes of both ventricles and to see if there is any relationship with clinical donor organ failure.
  
  
  METHODS
  Twelve patients undergoing heart or heart-lung transplantation (including three domino cases) were studied with transmural biopsies from the right (RV) and the left ventricles (LV) at the following points: after donor optimisation; at the end of ischaemic time; and after 10 min of reperfusion. The 1-week endomyocardial RV biopsy was also examined. Five donor hearts turned down purely on functional grounds were analysed also.
  
  
  RESULTS
  There was no difference between the RV and the LV for any of the markers at intraoperative assessment. The pattern of expression was not predictive of allograft failure. Donor hearts, however, have a strong pro-apoptotic phenotype, which is largely unopposed by the protective factors Bcl-2 and Hsp-70. Furthermore, the intensity of myocyte staining increases over time for Bax (P<0.001) and iNOs (P=0.02). Domino hearts showed a similar pattern. Compared to usable organs, poorly functioning donor hearts have stronger myocardial staining for Bax (P=0.002) and iNOs (P=0.01).
  
  
  CONCLUSIONS
  Clinical cardiac transplantation is associated with activation of the Bax and iNOs pathways in both ventricles. The myocardium is affected in time-dependent fashion but this is compatible, to a certain extent, with satisfactory allograft function. Donor hearts turned down on the basis of poor haemodynamic performance have significantly higher expression of Bax and iNOs.
authors.affiliation: Department of Transplantation, Papworth Hospital, Cambridge, UK.
authors.forename: Serban C
authors.initials: SC
authors.lastname: Stoica
authors.forename: Duwarakan K
authors.initials: DK
authors.lastname: Satchithananda
authors.forename: Carl
authors.initials: C
authors.lastname: Atkinson
authors.forename: Susan
authors.initials: S
authors.lastname: Charman
authors.forename: Martin
authors.initials: M
authors.lastname: Goddard
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Large
mesh_terms: D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007432:Intraoperative Period; D008137:Longitudinal Studies; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011184:Postoperative Period; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II