title: Donor pretreatment with hypertonic saline attenuates primary allograft dysfunction: a pilot study in a porcine model.
abstract: 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.
authors.affiliation: Peter Munk Cardiac Centre, Toronto General Hospital-University Health Network, Ontario, Canada.
authors.forename: Mitesh V
authors.initials: MV
authors.lastname: Badiwala
authors.forename: Danny
authors.initials: D
authors.lastname: Ramzy
authors.forename: Laura C
authors.initials: LC
authors.lastname: Tumiati
authors.forename: Elissa D
authors.initials: ED
authors.lastname: Tepperman
authors.forename: Rohit
authors.initials: R
authors.lastname: Sheshgiri
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Prodger
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Feindel
authors.forename: Vivek
authors.initials: V
authors.lastname: Rao
mesh_terms: 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
chemical_list: D016207:Cytokines; D012462:Saline Solution, Hypertonic; D012964:Sodium