Sanaz Hatami1, Christopher W White1, Shubham Shan2, Alois Haromy3, Xiao Qi1, Martin Ondrus4, Alexandra Kinnear4, Sayed Himmat1, Evangelos Michelakis3, Jayan Nagendran5, Darren H Freed6. 1. Department of Surgery, University of Alberta, Edmonton, Alberta, Canada; Canadian Transplant Research Program, Canada. 2. Department of Physiology, University of Alberta, Edmonton, Alberta, Canada. 3. Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. 4. Department of Surgery, University of Alberta, Edmonton, Alberta, Canada. 5. Department of Surgery, University of Alberta, Edmonton, Alberta, Canada; Canadian Transplant Research Program, Canada; Alberta Transplant Institute, Edmonton, Alberta, Canada. 6. Department of Surgery, University of Alberta, Edmonton, Alberta, Canada; Canadian Transplant Research Program, Canada; Department of Physiology, University of Alberta, Edmonton, Alberta, Canada; Alberta Transplant Institute, Edmonton, Alberta, Canada; Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada. Electronic address: dhfreed@ualberta.ca.
Abstract
BACKGROUND: Myocardial function declines in a time-dependent fashion during ex situ heart perfusion. Cell death and metabolic alterations may contribute to this phenomenon, limiting the safe perfusion period and the potential of ex situ heart perfusion to expand the donor pool. Our aim was to investigate the etiology of myocardial functional decline in ex situ perfused hearts. METHODS: Cardiac function, apoptosis, effectors and markers of cell death, and metabolic function were assessed in healthy pig hearts perfused for 12 hours. These hearts were perfused in nonworking mode or working mode. RESULTS: Cardiac function declined during ex situ heart perfusion regardless of perfusion mode but was significantly better preserved in the hearts perfused in working mode (11-hour cardiac index/1-hour cardiac index: working mode, 33%; nonworking mode, 10%; p = 0.025). The rate of apoptosis was higher in the ex situ perfused hearts compared with in vivo samples (apoptotic cells: in vivo, 0.13%; working mode, 0.54%; nonworking mode, 0.88%; p < 0.001), but the absolute values were low and out of proportion to the decline in function in either group. Myocardial dysfunction at the end of the perfusion interval was partially rescued by delivery of a pyruvate bolus. CONCLUSIONS: A significant decline in myocardial function occurs over time in hearts preserved ex situ that is out of proportion to the magnitude of myocyte cell death present in dysfunctional hearts. Alterations in myocardial substrate utilization during prolonged ex situ heart perfusion may contribute to this phenomenon and represent an avenue to improve donor heart preservation.
BACKGROUND:Myocardial function declines in a time-dependent fashion during ex situ heart perfusion. Cell death and metabolic alterations may contribute to this phenomenon, limiting the safe perfusion period and the potential of ex situ heart perfusion to expand the donor pool. Our aim was to investigate the etiology of myocardial functional decline in ex situ perfused hearts. METHODS: Cardiac function, apoptosis, effectors and markers of cell death, and metabolic function were assessed in healthy pig hearts perfused for 12 hours. These hearts were perfused in nonworking mode or working mode. RESULTS: Cardiac function declined during ex situ heart perfusion regardless of perfusion mode but was significantly better preserved in the hearts perfused in working mode (11-hour cardiac index/1-hour cardiac index: working mode, 33%; nonworking mode, 10%; p = 0.025). The rate of apoptosis was higher in the ex situ perfused hearts compared with in vivo samples (apoptotic cells: in vivo, 0.13%; working mode, 0.54%; nonworking mode, 0.88%; p < 0.001), but the absolute values were low and out of proportion to the decline in function in either group. Myocardial dysfunction at the end of the perfusion interval was partially rescued by delivery of a pyruvate bolus. CONCLUSIONS: A significant decline in myocardial function occurs over time in hearts preserved ex situ that is out of proportion to the magnitude of myocyte cell death present in dysfunctional hearts. Alterations in myocardial substrate utilization during prolonged ex situ heart perfusion may contribute to this phenomenon and represent an avenue to improve donor heart preservation.
Authors: Thomas Duignan; Alvise Guariento; Ilias P Doulamis; Takashi Kido; William L Regan; Mossab Saeed; David M Hoganson; Sitaram M Emani; Pedro J Del Nido; James D McCully; Gregory S Matte Journal: J Extra Corpor Technol Date: 2020-12
Authors: Vincent van Suylen; Katrien Vandendriessche; Arne Neyrinck; Foppe Nijhuis; Arjan van der Plaats; Erik K Verbeken; Pieter Vermeersch; Bart Meyns; Massimo A Mariani; Filip Rega; Michiel E Erasmus Journal: Artif Organs Date: 2021-10-31 Impact factor: 2.663