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.


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.
Badiwala
Mitesh V
MV
Peter Munk Cardiac Centre, Toronto General Hospital-University Health Network, Ontario, Canada.
Ramzy
Danny
D
Tumiati
Laura C
LC
Tepperman
Elissa D
ED
Sheshgiri
Rohit
R
Prodger
Jessica L
JL
Feindel
Christopher M
CM
Rao
Vivek
V
D000818:Animals; D002315:Cardiopulmonary Bypass; D016207:Cytokines / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects* / Q000401:mortality; D023421:Models, Animal; D055031:Primary Graft Dysfunction / Q000517:prevention & control*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D012964:Sodium / Q000097:blood; D013552:Swine; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016277:Ventricular Function, Left
D016207:Cytokines; D012462:Saline Solution, Hypertonic; D012964:Sodium