Dialysis preserves heart function during ex situ heart perfusion
Frank Yu, MSc,
Roberto Ribeiro, MD, PhD,
Roizar Rosales, MD,
Ludger Hauck, PhD,
Daniela Grothe,
Juglans Alvarez, MD,
Mitchell Adamson, MSc,
Vivek Rao, MD, PhD,
Mitesh Badiwala, MD, PhD,
Filio Billia, MD, PhD
Affiliations
Frank Yu, MSc
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
Roberto Ribeiro, MD, PhD
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
Roizar Rosales, MD
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
Ludger Hauck, PhD
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
Daniela Grothe
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
Juglans Alvarez, MD
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Division of Cardiovascular Surgery, Peter Munk Cardiac Center, Toronto Ontario, Canada; Ajmera Transplant Center, University Health Network, Toronto Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada
Mitchell Adamson, MSc
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
Vivek Rao, MD, PhD
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Division of Cardiovascular Surgery, Peter Munk Cardiac Center, Toronto Ontario, Canada; Ajmera Transplant Center, University Health Network, Toronto Ontario, Canada; Department of Surgery, University of Toronto, Toronto, Ontario, Canada
Mitesh Badiwala, MD, PhD
Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Heart, Vascular and Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates; Corresponding author. Mitesh Badiwala MD, PhD, Cleveland Clinic Abu Dhabi, PO Box 112412, Abu Dhabi, United Arab Emirates.
Filio Billia, MD, PhD
Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada; Ajmera Transplant Center, University Health Network, Toronto Ontario, Canada; Ted Rogers Center for Heart Research, University Health Network, Toronto Ontario, Canada; Division of Cardiology, Peter Munk Cardiac Center, Toronto Ontario, Canada; Corresponding author. Filio Billia, MD, PhD, 200 Elizabeth St., Rm 6EN-242, Toronto, ON M5G 2N2, Canada.
Background: Ex situ heart perfusion (ESHP) has been used to optimize donor organs before heart transplantation. However, cardiac function often deteriorates with the development of myocardial edema. The use of dialysis during ESHP could assist in cardiac preservation. Methods: Male Yorkshire pig hearts were subjected to ESHP for 8 hours with or without dialysis. Hearts were supported during nonworking mode and working mode, and pressure-volume loops and coronary vasomotor function were evaluated. Finally, tissue biopsies were assessed for mitochondrial function, oxidative stress, and inflammation. Results: Adding dialysis to ESHP significantly enhanced cardiac function, with improved preload recruitable stroke work at 4 hours (64.09 ± 20.13 vs 35.08 ± 13.52, p = 0.010) and 8 hours (64.31 ± 9.08 vs 23.30 ± 19.25, p = 0.0002), maximal elastance at 8 hours (24.67 ± 10.75 vs 10.62 ± 8.471, p = 0.0477), and end diastolic pressure volume relationship at 8 hours (644.7 ± 566.68 vs 86.63 ± 72.05, p = 0.0187). Coronary vasomotor function improved in the dialysis group in endothelium dependent (LogIC50 −7.39 ± 0.25 vs −2.22 ± 0.76, p < 0.0001) and independent (LogIC50 −6.11 ± 0.19 vs −4.79 ± 0.11, p < 0.0001) vasorelaxation. Dialyzed hearts also had reduced sensitivity to endothelin-1 (LogEC50 −7.94 ± 0.5 vs −8.54 ± 0.06, p = 0.0449) and significant changes in endothelin receptor-related protein expression related and oxidative stress. Conclusions: The combination of dialysis with ESHP improves myocardial and coronary vasomotor preservation and may allow for longer perfusion times.
