Christopher White1, Emma Avery2, Alison Müller3, Sanaz Hatami3, Yun Li2, Hoa Le2, James Thliveris4, Rakesh Arora5, Trevor Lee6, Ian Dixon2, Ganghong Tian7, Jayan Nagendran8, Larry Hryshko2, Darren Freed9. 1. Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada; Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada; Department of Surgery, University of Alberta, Edmonton, Canada. 2. Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada. 3. Department of Physiology, University of Alberta, Edmonton, Canada. 4. Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada. 5. Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada; Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada. 6. Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. 7. National Research Council Institute for Biodiagnostics, Winnipeg, Manitoba, Canada. 8. Department of Surgery, University of Alberta, Edmonton, Canada; Department of Physiology, University of Alberta, Edmonton, Canada. 9. Institute of Cardiovascular Sciences, St. Boniface Research Center, Winnipeg, Manitoba, Canada; Department of Surgery, University of Alberta, Edmonton, Canada; Department of Physiology, University of Alberta, Edmonton, Canada; Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada. Electronic address: dhfreed@ualberta.ca.
Abstract
BACKGROUND: Hearts donated after circulatory death may represent an additional donor source. The influx of sodium and calcium ions across the sarcolemma play a central role in the pathogenesis of ischemia-reperfusion injury; however, this process may be inhibited if the initial reperfusion solution is rendered hypocalcemic and acidic. We sought to determine the calcium concentration and pH of the initial reperfusion solution that yielded optimal functional recovery of hearts donated after circulatory death during ex vivo heart perfusion. METHODS: Pigs were anesthetized, mechanical ventilation was discontinued, and a 15-minute standoff period was observed after circulatory arrest. Hearts were reperfused with a normothermic cardioplegia of varying calcium concentrations (part 1 [50 μmol/L, n = 4; 220 μmol/L, n = 9; 500 μmol/L, n = 4; and 1,250 μmol/L, n = 5]) and pH (part 2 [7.9, n = 5; 7.4, n = 9; 6.9, n = 8; and 6.4, n = 6]). Myocardial function was then assessed in a physiologic working model 1 hour after initiation of normothermic ex vivo heart perfusion. RESULTS: The calcium concentration and pH of the cardioplegic solution affected the development of myocardial edema (part 1: 50 μmol/L = 5.8% ± 0.9%; 220 μmol/L = 4.3% ± 0.4%; 500 μmol/L = 7.0% ± 0.6%; and 1,250 μmol/L = 6.6% ± 0.8% weight gain, p = 0.015; part 2: 7.9 = 3.6% ± 0.4%, 7.4 = 4.3% ± 0.4%, 6.9 = 3.7% ± 0.6%, and 6.4 = 6.4% ± 1.3% weight gain, p = 0.056) and the recovery of myocardial function (cardiac index part 1: 50 μmol/L = 2.6 ± 0.6; 220 μmol/L = 6.0 ± 0.8; 500 μmol/L = 2.3 ± 0.5; and 1,250 μmol/L = 1.9 ± 0.6 mL · m-1 · g-1, p < 0.001; part 2: 7.9 = 1.5 ± 0.7; 7.4 = 6.0 ± 0.8; 6.9 = 8.4 ± 1.8; and 6.4 = 3.1 ± 0.8 mL · m-1 · g-1, p = 0.003) during ex vivo heart perfusion. CONCLUSIONS: Initial reperfusion of hearts donated after circulatory death with a hypocalcemic and moderately acidic cardioplegia minimizes edema and optimizes functional recovery during subsequent ex vivo heart perfusion.
BACKGROUND: Hearts donated after circulatory death may represent an additional donor source. The influx of sodium and calcium ions across the sarcolemma play a central role in the pathogenesis of ischemia-reperfusion injury; however, this process may be inhibited if the initial reperfusion solution is rendered hypocalcemic and acidic. We sought to determine the calcium concentration and pH of the initial reperfusion solution that yielded optimal functional recovery of hearts donated after circulatory death during ex vivo heart perfusion. METHODS: Pigs were anesthetized, mechanical ventilation was discontinued, and a 15-minute standoff period was observed after circulatory arrest. Hearts were reperfused with a normothermic cardioplegia of varying calcium concentrations (part 1 [50 μmol/L, n = 4; 220 μmol/L, n = 9; 500 μmol/L, n = 4; and 1,250 μmol/L, n = 5]) and pH (part 2 [7.9, n = 5; 7.4, n = 9; 6.9, n = 8; and 6.4, n = 6]). Myocardial function was then assessed in a physiologic working model 1 hour after initiation of normothermic ex vivo heart perfusion. RESULTS: The calcium concentration and pH of the cardioplegic solution affected the development of myocardial edema (part 1: 50 μmol/L = 5.8% ± 0.9%; 220 μmol/L = 4.3% ± 0.4%; 500 μmol/L = 7.0% ± 0.6%; and 1,250 μmol/L = 6.6% ± 0.8% weight gain, p = 0.015; part 2: 7.9 = 3.6% ± 0.4%, 7.4 = 4.3% ± 0.4%, 6.9 = 3.7% ± 0.6%, and 6.4 = 6.4% ± 1.3% weight gain, p = 0.056) and the recovery of myocardial function (cardiac index part 1: 50 μmol/L = 2.6 ± 0.6; 220 μmol/L = 6.0 ± 0.8; 500 μmol/L = 2.3 ± 0.5; and 1,250 μmol/L = 1.9 ± 0.6 mL · m-1 · g-1, p < 0.001; part 2: 7.9 = 1.5 ± 0.7; 7.4 = 6.0 ± 0.8; 6.9 = 8.4 ± 1.8; and 6.4 = 3.1 ± 0.8 mL · m-1 · g-1, p = 0.003) during ex vivo heart perfusion. CONCLUSIONS: Initial reperfusion of hearts donated after circulatory death with a hypocalcemic and moderately acidic cardioplegia minimizes edema and optimizes functional recovery during subsequent ex vivo heart perfusion.
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; Eline M Bunnik; Johanna A M Hagenaars; Imran A Ertugrul; Jan A M Bollen; Massimo A Mariani; Michiel E Erasmus Journal: Transplant Direct Date: 2021-02-22
Authors: Emilie Farine; Petra Niederberger; Rahel K Wyss; Natalia Méndez-Carmona; Brigitta Gahl; Georg M Fiedler; Thierry P Carrel; Hendrik T Tevaearai Stahel; Sarah L Longnus Journal: Front Physiol Date: 2016-11-22 Impact factor: 4.566
Authors: Christopher W White; Simon J Messer; Stephen R Large; Jennifer Conway; Daniel H Kim; Demetrios J Kutsogiannis; Jayan Nagendran; Darren H Freed Journal: Front Cardiovasc Med Date: 2018-02-13