Abstract 12101: Adenosine Injection Prior to Cardioplegia Enhances Preservation of Senescent Hearts in Rat Heterotopic Heart Transplantation
Introduction: Because of the shortage of donors and lengthy transplant waiting list, utilization of hearts from older donors is increasing. However, outcome after transplant correlates inversely with donor age, with a high incidence of primary graft failure in grafts from older donors. Improving donor heart preservation may improve outcomes. Adenosine protects the myocardium from ischemic damage, but its effects on senescent hearts are unknown.
Hypothesis: A bolus injection of adenosine before cardioplegia perfusion may ameliorate cold ischemia/reperfusion injury during transplant of hearts from older donors.
Methods: We used a rat heterotopic heart transplantation model with 60-week old Lewis rats as donors (n=7 per group). We injected saline (1 ml; control) or adenosine (0.1 or 0.2 mg/kg in 1 ml saline) before cardioplegia perfusion with 3 ml of cold Celsior, and stored in Celsior for 6 hours at 4°C. The grafts were transplanted into syngenic, 12-16 week-old recipients and reperfused for 3 hours. Serum troponin I and CPK, and graft proinflammatory mRNA levels were analyzed as markers of graft injury.
Results: Bolus injection of adenosine led to significantly faster cardiac arrest after infusion of Celsior and faster reanimation after reperfusion compared with controls. Adenosine significantly reduced myocardial injury, as indicated by serum troponin I and CPK levels 3 hours after reperfusion. The mRNAs for IL-6, ICAM-1 and TNF-α were markedly increased in the control grafts. The grafts with adenosine treatment exhibited less upregulation of these proinflammatory mRNAs and had fewer infiltrating cells in histopathological analysis.
Conclusions: Adenosine injection prior to perfusion of cardioplegia significantly reduced cold ischemia/reperfusion injury in cardiac grafts from older donors. This procurement protocol may be clinically feasible and should be considered in the clinical setting, in particular for older donors.
- © 2011 by American Heart Association, Inc.