title: The initial rate of troponin I release post-reperfusion reflects the effectiveness of myocardial protection during cardiac allograft preservation.
abstract: OBJECTIVE
  To determine if the initial rate of troponin I release post-reperfusion reflects the effectiveness of myocardial protection during cardiac allograft preservation.
  
  
  METHODS
  A porcine model of orthotopic heart transplantation was used. Data from two control groups (CON(4) and CON(14)) and two treatment groups (CAR(4) and CAR(14)) were analysed. Hearts in CON(4) (n=6) and CAR(4) (n=6) were subjected to 4 h of ischaemia while hearts in CON(14) (n=3) and CAR(14) (n=6) were subjected to 14 h of ischaemia. All hearts were arrested and stored in the same extracellular preservation solution. Both donor and recipient animals in the CAR(4) and CAR(14) groups received a single intravenous dose of cariporide (2 mg/kg), prior to explantation and reperfusion, respectively.
  
  
  RESULTS
  Mean (SEM) plasma troponin I levels (microg/ml) 3 h post-reperfusion were: CON(4) 210+/-52, CAR(4) 68+/-21, CON(14) 633+/-177, CAR(14) 346+/-93. On multiple linear regression analysis, the rate of troponin I release over the first 3 h post-reperfusion was significantly lower in hearts stored for 4 h compared to hearts stored for 14 h (P<0.0001) and in hearts treated with cariporide compared to control hearts (P=0.0017). Early graft function was superior in hearts treated with cariporide, when compared to control hearts stored for the same period of time. All of the CAR(14) hearts could be weaned from cardiopulmonary bypass whereas none of the CON(14) could be weaned (6/6 vs. 0/3; P=0.012). While all hearts stored for 4 h could be weaned, contractility, as measured by the preload recruitable stroke work (PRSW) relationship, was significantly better preserved in CAR(4) hearts than in CON(4) hearts (P<0.0001).
  
  
  CONCLUSIONS
  The initial rate of troponin I release post-reperfusion is determined by the duration of cardiac allograft ischaemia. Altering the myocardial preservation strategy can reduce the rate of release. Such reductions are associated with improvements in early graft function. These findings validate the initial rate of troponin I release post-reperfusion as an end-point when comparing cardiac allograft preservation strategies. In addition, the present study provides indirect evidence that troponin I degradation during ischaemia-reperfusion is related to the accumulation of intracellular calcium.
authors.affiliation: Heart and Lung Transplant Unit, St. Vincent's Hospital and the Victor Chang Cardiac Research Institute, Sydney, Australia. j.ryan@garvan.unsw.edu.au
authors.forename: Jonathon B
authors.initials: JB
authors.lastname: Ryan
authors.forename: Mark
authors.initials: M
authors.lastname: Hicks
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Cropper
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Garlick
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kesteven
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wilson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Feneley
authors.forename: Peter S
authors.initials: PS
authors.lastname: Macdonald
mesh_terms: D000818:Animals; D017849:Animals, Inbred Strains; D006146:Guanidines / Q000627:therapeutic use; D016027:Heart Transplantation; D023421:Models, Animal; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis*; D011184:Postoperative Period; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D013450:Sulfones / Q000627:therapeutic use; D013552:Swine; D013997:Time Factors; D014021:Tissue Preservation / Q000379:methods; D014184:Transplantation, Homologous; D019210:Troponin I / Q000097:blood*
chemical_list: D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D019210:Troponin I; C093373:cariporide