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, 0.56 10 to 6 0.23 mol/L; control, 2.5 10 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.)