Omar A Mownah1, Muhammad A Khurram2, Christopher Ray2, Aditya Kanwar2, Susan Stamp3, Douglas Rees4, John Brassil5, Joaquim Majo6, John H Dark7, Noel M Carter8, David Talbot9. 1. Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK; Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, UK. Electronic address: omar.mownah@gmail.com. 2. Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK; Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, UK. 3. Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK. 4. AQIX, Ltd, London BioScience Innovation Centre, London, UK. 5. Functional Circulation LLC, Northbrook, Illinois. 6. Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK. 7. Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK; Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, UK. 8. Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, UK. 9. Institute of Transplantation, Freeman Hospital, Newcastle Upon Tyne, UK; Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, UK. Electronic address: david.talbot@nuth.nhs.uk.
Abstract
BACKGROUND: This study reports on the development of a novel method for achieving ex vivo reanimation of hearts from a porcine donation after circulatory death (DCD) model without the use of donor pretreatment. METHODS: Porcine hearts (n = 23) were procured 10-29 min after confirmation of asystole. All hearts underwent initial flush with AQIX RS-I solution (London, UK). A 2-h preservation period followed: group 1 hearts (n1-n11) were preserved using static cold storage, group 2 hearts (n12-n17) were preserved using oxygenated, hypothermic machine perfusion (MP), and group 3 hearts (n18-n23) were subjected to retrograde oxygen persufflation. Reperfusion was performed on a Langendorff modification of a Model 33 Functional Circulation circuit. In hearts n16-n23, a dialysis circuit was incorporated into the circuit to facilitate removal of metabolites. The experimental protocol was allowed to follow an evolutionary course, with the aim of achieving greater success with reanimation. RESULTS: In group 1 (static cold storage), 7 of the 11 hearts (63.6%) achieved reanimation on the ex vivo circuit. Two of the six hearts (33.3%) in group 2 (MP) were successfully reanimated. All the six hearts (100%) in group 3 (persufflation) were successfully reanimated. The period of sustained reanimation increased when dialysis was incorporated into the circuit with a maximum of 300 min. CONCLUSIONS: Porcine DCD hearts after 29 min of warm ischemia can be reanimated using the method described. A mechanism of reoxygenation (oxygenated MP or coronary sinus oxygen persufflation) during preservation appears mandatory for hearts from DCDs. Persufflation was associated with a higher probability of successful reanimation. Dialysis in the warm phase was useful in removing metabolites that could interfere with reanimation. The results demonstrate the potential of DCDs to counter the decline affecting heart transplantation.
BACKGROUND: This study reports on the development of a novel method for achieving ex vivo reanimation of hearts from a porcine donation after circulatory death (DCD) model without the use of donor pretreatment. METHODS: Porcine hearts (n = 23) were procured 10-29 min after confirmation of asystole. All hearts underwent initial flush with AQIX RS-I solution (London, UK). A 2-h preservation period followed: group 1 hearts (n1-n11) were preserved using static cold storage, group 2 hearts (n12-n17) were preserved using oxygenated, hypothermic machine perfusion (MP), and group 3 hearts (n18-n23) were subjected to retrograde oxygen persufflation. Reperfusion was performed on a Langendorff modification of a Model 33 Functional Circulation circuit. In hearts n16-n23, a dialysis circuit was incorporated into the circuit to facilitate removal of metabolites. The experimental protocol was allowed to follow an evolutionary course, with the aim of achieving greater success with reanimation. RESULTS: In group 1 (static cold storage), 7 of the 11 hearts (63.6%) achieved reanimation on the ex vivo circuit. Two of the six hearts (33.3%) in group 2 (MP) were successfully reanimated. All the six hearts (100%) in group 3 (persufflation) were successfully reanimated. The period of sustained reanimation increased when dialysis was incorporated into the circuit with a maximum of 300 min. CONCLUSIONS: Porcine DCD hearts after 29 min of warm ischemia can be reanimated using the method described. A mechanism of reoxygenation (oxygenated MP or coronary sinus oxygen persufflation) during preservation appears mandatory for hearts from DCDs. Persufflation was associated with a higher probability of successful reanimation. Dialysis in the warm phase was useful in removing metabolites that could interfere with reanimation. The results demonstrate the potential of DCDs to counter the decline affecting heart transplantation.
Authors: Alyssa Ward; David K Klassen; Kate M Franz; Sebastian Giwa; Jedediah K Lewis Journal: Curr Opin Organ Transplant Date: 2018-06 Impact factor: 2.640