title: The energy metabolism in the right and left ventricles of human donor hearts across transplantation.
abstract: OBJECTIVE
  Brain death appears to predominantly affect the right ventricle (RV) and right ventricular failure is a common complication of clinical cardiac transplantation. It is not clear to what extent myocardial energy stores are affected in the operative sequence. We aimed to describe the time-dependent variation in high energy phosphate (HEP) metabolism of the two ventricles, and the relationship with endothelial activation and postoperative functional recovery.
  
  
  METHODS
  Fifty-two human donors had serial biopsies from the RV and the left ventricle (LV) at (1) initial evaluation, (2) after haemodynamic optimisation, (3) end of cold ischaemia, (4) end of warm ischaemia, (5) reperfusion, and (6) at 1 week postoperatively. HEP was measured by chemiluminescence in biopsies 1-5 and adhesion molecules (P-selectin, E-selectin, VCAM-1) and thrombomodulin were analysed by immunohistochemistry in biopsies 5-6. Seventeen donors and five recipients had RV intraoperative pressure-volume recordings by a conductance catheter. Six patients served as live controls.
  
  
  RESULTS
  Brain death did not affect HEP metabolism quantitatively. There was no difference between the RV and LV at any time point, but significant time-dependent changes were observed. The RV was prone to HEP depletion at retrieval, with ATP/ADP falling from 3.89 to 3.13, but recovered during cold ischaemia. During warm ischaemia the ATP/ADP ratio fell by approximately 50%, from 5.48 for the RV and 4.26 for the LV, with partial recovery at reperfusion (P<0.005). Hearts with impaired function in the recipient showed marked variations in HEP levels at reperfusion, and those organs with RV dysfunction failed to replenish their energy stores. However, these organs were not different from normally functioning allografts in terms of endothelial activation and clinical risk factors. There was poor correlation between pressure-volume and HEP data in either donor or recipient studies. Hearts followed-up with HEP and pressure-volume studies showed improvement in the recipient, despite functioning against a higher pulmonary vascular resistance.
  
  
  CONCLUSIONS
  HEP are preserved over a wide range of contractile performance in the donor heart, with no metabolic difference between the two ventricles. No correlation with endothelial activation was seen either. Preservation efforts should be directed to the vulnerable periods of implantation and reperfusion.
authors.affiliation: Department of Transplantation, Papworth Hospital, Cambridge CB3 8RE, 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: Paul A
authors.initials: PA
authors.lastname: White
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Redington
authors.forename: Martin
authors.initials: M
authors.lastname: Goddard
authors.forename: Terence
authors.initials: T
authors.lastname: Kealey
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Large
mesh_terms: D000328:Adult; D001926:Brain Death / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D004734:Energy Metabolism; D016027:Heart Transplantation / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D010710:Phosphates