Donor pretreatment with hypertonic saline attenuates primary allograft dysfunction A pilot study in a porcine model

Mitesh V. Badiwala, Danny Ramzy, Laura C. Tumiati, Elissa D. Tepperman, Rohit Sheshgiri, Jessica L. Prodger, Christopher M. Feindel, Vivek Rao

Research output: Contribution to journalArticlepeer-review

Abstract

Background-Hypertonie 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; f=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=OM). 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.

Original languageEnglish (US)
Pages (from-to)S206-S214
JournalCirculation
Volume120
Issue numberSUPPL. 1
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Endothelium
  • Ischemia
  • Reperfusion
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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