title: Pathophysiological Trends During Withdrawal of Life Support: Implications for Organ Donation After Circulatory Death.
abstract: BACKGROUND
  Donation after circulatory death (DCD) provides an alternative pathway to deceased organ transplantation. Although clinical DCD lung, liver, and kidney transplantation are well established, transplantation of hearts retrieved from DCD donors has reached clinical translation only recently. Progress has been limited by concern regarding the viability of DCD hearts. The aim of this study was to document the pathophysiological changes that occur in the heart and circulation during withdrawal of life (WLS) support.
  
  
  METHODS
  In a porcine asphyxia model, we characterized the hemodynamic, volumetric, metabolic, biochemical, and endocrine changes after WLS for up to 40 minutes. Times to circulatory arrest and electrical asystole were recorded.
  
  
  RESULTS
  After WLS, there was rapid onset of profound hypoxemia resulting in acute pulmonary hypertension and right ventricular distension. Concurrently, progressive systemic hypotension occurred with a fall in left atrial pressure and little change in left ventricular volume. Mean times to circulatory arrest and electrical asystole were 8 ± 1 and 16 ± 2 minutes, respectively. Hemodynamic changes were accompanied by a rapid fall in pH, and rise in blood lactate, troponin-T, and potassium. Plasma noradrenaline and adrenaline levels rose rapidly with dramatic increases in coronary sinus levels indicative of myocardial release.
  
  
  CONCLUSIONS
  These findings provide insight into the nature and tempo of the damaging events that occur in the heart and in particular the right ventricle during WLS, and give an indication of the limited timeframe for the implementation of potential postmortem interventions that could be applied to improve organ viability.
authors.affiliation: 1 The Victor Chang Cardiac Research Institute, Sydney, Australia. 2 Heart & Lung Transplant Unit, St Vincent's Hospital, Darlinghurst, Australia. 3 Department of Cardiothoracic Surgery, St Vincent's Hospital, Darlinghurst, Australia. 4 Department of Clinical Pharmacology, St Vincent's Hospital, Darlinghurst, Australia. 5 Department of Physiology and Pharmacology, University of New South Wales, Randwick, Australia. 6 Department of Cardiology, St Vincent's Hospital, Darlinghurst, Australia. 7 St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Kensington, Australia. 8 School of Biotechnology and Biomolecular Science, Faculty of Science, University of New South Wales, Kensington, Australia.
authors.forename: Arjun
authors.initials: A
authors.lastname: Iyer
authors.forename: Hong Chee
authors.initials: HC
authors.lastname: Chew
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Jeanette
authors.initials: J
authors.lastname: Villanueva
authors.forename: Mark
authors.initials: M
authors.lastname: Hicks
authors.forename: Aoife
authors.initials: A
authors.lastname: Doyle
authors.forename: Gayathri
authors.initials: G
authors.lastname: Kumarasinghe
authors.forename: Andrew
authors.initials: A
authors.lastname: Jabbour
authors.forename: Paul Cassius
authors.initials: PC
authors.lastname: Jansz
authors.forename: Michael P
authors.initials: MP
authors.lastname: Feneley
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harvey
authors.forename: Robert M
authors.initials: RM
authors.lastname: Graham
authors.forename: Kumud K
authors.initials: KK
authors.lastname: Dhital
authors.forename: Peter S
authors.initials: PS
authors.lastname: Macdonald
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000473:pathology; D001784:Blood Gas Analysis; D001794:Blood Pressure; D003643:Death; D004837:Epinephrine / Q000097:blood; D006321:Heart; D006323:Heart Arrest / Q000503:physiopathology; D016027:Heart Transplantation / Q000379:methods*; D006439:Hemodynamics; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000097:blood; D009206:Myocardium / Q000473:pathology; D009638:Norepinephrine / Q000097:blood; D011188:Potassium / Q000097:blood; D013552:Swine; D013997:Time Factors; D014019:Tissue Donors; D014022:Tissue Survival; D009927:Tissue and Organ Procurement / Q000379:methods*; D020107:Troponin T / Q000097:blood; D052096:Warm Ischemia
chemical_list: D007773:Lactates; D020107:Troponin T; D011188:Potassium; D009638:Norepinephrine; D004837:Epinephrine