Donor Pretreatment With Hypertonic Saline Attenuates Primary Allograft Dysfunction A Pilot Study in a Porcine Model

Background-Hypertonic saline (HTS) has been previously demonstrated to have immune modulatory and vascular protective effects. We assessed the effect of donor pretreatment with HTS on allograft preservation in a porcine model of orthotopic heart transplantation. Methods and Results-Orthotopic transplants were performed after 6 hours of cold static allograft storage. Donor pigs were randomly assigned to pretreatment with (n=7) or without (n=6) HTS (4.5 mL/kg of 7.5% NaCl) administered 1 hour before donor heart arrest. Administration of HTS increased serum sodium level from 138 +/- 2 mmol/L to 154 +/- 4 mmol/L, which normalized to 144 +/- 3 mmol/L 1 hour after infusion. Successful weaning from cardiopulmonary bypass was significantly greater in HTS-treated hearts (6/7 vs 1/6; P=0.029). Preload recruitable stroke work after transplantation was improved compared to control (88 +/- 21% vs 35 +/- 8% of baseline; P=0.0001). Similarly, end-systolic elastance was improved compared to control (85 +/- 17% vs 42 +/- 12% of baseline; P=0.0002). Posttransplantation systolic blood pressure was significantly higher in the donor HTS group (60 +/- 9 mm Hg vs 35 +/- 6 mm Hg; P=0.04). Donor HTS treatment improved coronary artery endothelial-dependent vasorelaxation compared with control (Emax: HTS, 59 +/- 4%; control, 47 +/- 3%; P=0.04). HTS also resulted in improved endothelial-independent vasorelaxation compared with control (Emax: HTS, 71 +/- 3%; control, 59 +/- 4%; P=0.03; ED-50: HTS, 0.56X10 to 6 +/- 0.23 mol/L; control, 2.5X10 to 6 +/- 1.0 mol/L; P=0.04). Sensitivity to endothelin-1-induced vasospasm was reduced with HTS pretreatment (% maximum contraction [Cmax]: HTS, 338 +/- 15%; control, 419 +/- 40%; P=0.01). Conclusions-Donor HTS pretreatment attenuates posttransplantation cardiac allograft myocardial dysfunction, improves posttransplantation systemic hemodynamic function, and preserves posttransplantation cardiac allograft vascular function. HTS may be a novel organ donor intervention to prevent primary graft dysfunction. (Circulation. 2009; 120[suppl 1]: S206-S214.)