This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Badiwala, M. V. Articles by Rao, V. PubMed Articles by Badiwala, M. V. Articles by Rao, V. Related Collections Contractile function Cell biology/structural biology Transplantation Endothelium/vascular type/nitric oxide Other Vascular biology

(Circulation. 2009;120:S206-S214.)
© 2009 American Heart Association, Inc.

Cardiac Transplantation and Surgery for Heart Failure

Donor Pretreatment With Hypertonic Saline Attenuates Primary Allograft Dysfunction

A Pilot Study in a Porcine Model

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

From Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital-University Health Network, Toronto, Ontario, Canada.

Correspondence to Vivek Rao, MD, PhD, Associate Professor of Surgery, Alfredo and Teresa DeGasperis Chair in Heart Failure Surgery, Division of Cardiovascular Surgery, Toronto General Hospital, University of Toronto, 4N-464, 200 Elizabeth Street, Toronto, Ontario M5G 2C4. E-mail vivek.rao{at}uhn.on.ca

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.

Key Words: endothelium • ischemia • transplantation • reperfusion