Roberto V P Ribeiro1,2, Juglans S Alvarez1, Frank Yu1, Emanuela Paradiso3, Mitchell B Adamson1,2, Giulia Maria Ruggeri3, Naoto Fukunaga1, Ved Bissoondath1, Cyril Serrick4, Massimiliano Meineri3,5, Heather Ross6,2, Vivek Rao1,2,7, Mitesh V Badiwala1,7. 1. Division of Cardiovascular Surgery (R.V.P.R., J.S.A., F.Y., M.B.A., N.F., V.B., V.R., M.V.B.), Toronto General Hospital, University Health Network, ON, Canada. 2. Institute of Medical Science (R.V.P.R., M.B.A., H.R., V.R.), University of Toronto, Canada. 3. Peter Munk Cardiac Center, Department of Anesthesia and Pain Management (E.P., G.M.R., M.M.), Toronto General Hospital, University Health Network, ON, Canada. 4. Perfusion and Anesthesia Services (C.S.), Toronto General Hospital, University Health Network, ON, Canada. 5. Department of Anesthesia (M.M.), University of Toronto, Canada. 6. Division of Cardiology (H.R.), Toronto General Hospital, University Health Network, ON, Canada. 7. Department of Surgery, Faculty of Medicine (V.R., M.V.B.), University of Toronto, Canada.
Abstract
BACKGROUND: There has been an increased interest in donation after circulatory death (DCD) to expand donor pool for cardiac transplantation. Normothermic regional perfusion (NRP) allows in situ assessment of DCD hearts, allowing only acceptable organs to be procured. We sought to determine if extended cold storage was possible for DCD hearts following NRP and to compare hearts stored using standard cold storage with a novel cardioprotective solution designed for room temperature storage. METHODS AND RESULTS: Donor pigs underwent hypoxic cardiac arrest (DCD) followed by 15 minutes of warm ischemia and resuscitation on NRP. They were then randomly assigned to static storage with histidine-tryptophan-ketoglutarate (HTK) at 4°C (HTK group, n=5) or SOM-TRN-001 at 21°C (SOM group, n=5). Conventional beating-heart donations were used as controls (n=4). Fourteen transplants were successfully performed. HTK hearts showed initial dysfunction following reperfusion; however, they demonstrated significant recovery up to 3 hours post-transplant. No significant differences were seen between HTK and control hearts post-transplantation (cardiac index: control 49.5±6% and HTK 48.5±5% of baseline). SOM improved myocardial preservation; hearts showed stable contractility after transplantation (cardiac index: 113.0±43% of NRP function) and improved diastolic function compared with HTK. Preservation in SOM also significantly reduced proinflammatory cytokine production and release following transplantation and partially prevented endothelial dysfunction. CONCLUSIONS: DCD hearts stored using a standard preservation solution demonstrated comparable post-transplantation myocardial function to standard controls. Thus, short periods of cold storage following successful NRP and documented adequate function is an acceptable strategy for DCD hearts. Preservation in SOM at room temperature is feasible and can improve cardiac recovery by minimizing endothelial dysfunction and tissue injury.
BACKGROUND: There has been an increased interest in donation after circulatory death (DCD) to expand donor pool for cardiac transplantation. Normothermic regional perfusion (NRP) allows in situ assessment of DCD hearts, allowing only acceptable organs to be procured. We sought to determine if extended cold storage was possible for DCD hearts following NRP and to compare hearts stored using standard cold storage with a novel cardioprotective solution designed for room temperature storage. METHODS AND RESULTS:Donorpigs underwent hypoxic cardiac arrest (DCD) followed by 15 minutes of warm ischemia and resuscitation on NRP. They were then randomly assigned to static storage with histidine-tryptophan-ketoglutarate (HTK) at 4°C (HTK group, n=5) or SOM-TRN-001 at 21°C (SOM group, n=5). Conventional beating-heart donations were used as controls (n=4). Fourteen transplants were successfully performed. HTK hearts showed initial dysfunction following reperfusion; however, they demonstrated significant recovery up to 3 hours post-transplant. No significant differences were seen between HTK and control hearts post-transplantation (cardiac index: control 49.5±6% and HTK 48.5±5% of baseline). SOM improved myocardial preservation; hearts showed stable contractility after transplantation (cardiac index: 113.0±43% of NRP function) and improved diastolic function compared with HTK. Preservation in SOM also significantly reduced proinflammatory cytokine production and release following transplantation and partially prevented endothelial dysfunction. CONCLUSIONS: DCD hearts stored using a standard preservation solution demonstrated comparable post-transplantation myocardial function to standard controls. Thus, short periods of cold storage following successful NRP and documented adequate function is an acceptable strategy for DCD hearts. Preservation in SOM at room temperature is feasible and can improve cardiac recovery by minimizing endothelial dysfunction and tissue injury.
Entities:
Keywords:
cytokines; heart transplantation; organ preservation; reperfusion injury; tissue and organ procurement; vascular endothelium; warm ischemia
Authors: Sam D Shemie; Sylvia Torrance; Lindsay Wilson; Laura Hornby; Janet MacLean; Jim Mohr; Clay Gillrie; Mitesh V Badiwala; Andrew Baker; Darren H Freed; Christy Simpson; Jeanne Teitelbaum; Diana Brodrecht; Andrew Healey Journal: Can J Anaesth Date: 2021-02-05 Impact factor: 6.713