Extending heart preservation to 24 h with normothermic perfusion

Cold static storage (CSS) for up to 6 h is the gold standard in heart preservation. Although some hearts stored over 6 h have been transplanted, longer CSS times have increased posttransplant morbimortality. Transmedics® Organ Care System (OCS™) is the only FDA-approved commercial system that provid...

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Main Authors: Brianna L. Spencer, Spencer K. Wilhelm, Christopher Stephan, Kristopher A. Urrea, Daniela Pelaez Palacio, Robert H. Bartlett, Daniel H. Drake, Alvaro Rojas-Pena
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-04-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2024.1325169/full
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author Brianna L. Spencer
Spencer K. Wilhelm
Christopher Stephan
Kristopher A. Urrea
Daniela Pelaez Palacio
Robert H. Bartlett
Daniel H. Drake
Daniel H. Drake
Alvaro Rojas-Pena
Alvaro Rojas-Pena
author_facet Brianna L. Spencer
Spencer K. Wilhelm
Christopher Stephan
Kristopher A. Urrea
Daniela Pelaez Palacio
Robert H. Bartlett
Daniel H. Drake
Daniel H. Drake
Alvaro Rojas-Pena
Alvaro Rojas-Pena
author_sort Brianna L. Spencer
collection DOAJ
description Cold static storage (CSS) for up to 6 h is the gold standard in heart preservation. Although some hearts stored over 6 h have been transplanted, longer CSS times have increased posttransplant morbimortality. Transmedics® Organ Care System (OCS™) is the only FDA-approved commercial system that provides an alternative to CSS using normothermic ex situ heart perfusion (NEHP) in resting mode with aortic perfusion (Langendorff method). However, it is also limited to 6 h and lacks an objective assessment of cardiac function. Developing a system that can perfuse hearts under NEHP conditions for >24 h can facilitate organ rehabilitation, expansion of the donor pool, and objective functional evaluation. The Extracorporeal Life Support Laboratory at the University of Michigan has worked to prolong NEHP to >24 h with an objective assessment of heart viability during NEHP. An NEHP system was developed for aortic (Langendorff) perfusion using a blood-derived perfusate (leukocyte/thrombocyte-depleted blood). Porcine hearts (n = 42) of different sizes (6–55 kg) were divided into five groups and studied during 24 h NEHP with various interventions in three piglets (small-size) heart groups: (1) Control NEHP without interventions (n = 15); (2) NEHP + plasma exchange (n = 5); (3) NEHP + hemofiltration (n = 10) and two adult-size (juvenile pigs) heart groups (to demonstrate the support of larger hearts); (4) NEHP + hemofiltration (n = 5); and (5) NEHP with intermittent left atrial (iLA) perfusion (n = 7). All hearts with NEHP + interventions (n = 27) were successfully perfused for 24 h, whereas 14 (93.3%) control hearts failed between 10 and 21 h, and 1 control heart (6.6%) lasted 24 h. Hearts in the piglet hemofiltration and plasma exchange groups performed better than those in the control group. The larger hearts in the iLA perfusion group (n = 7) allowed for real-time heart functional assessment and remained stable throughout the 24 h of NEHP. These results demonstrate that heart preservation for 24 h is feasible with our NEHP perfusion technique. Increasing the preservation period beyond 24 h, infection control, and nutritional support all need optimization. This proves the concept that NEHP has the potential to increase the organ pool by (1) considering previously discarded hearts; (2) performing an objective assessment of heart function; (3) increasing the donor/recipient distance; and (4) developing heart-specific perfusion therapies.
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spelling doaj.art-f13ecef17b1344c080eeebbddaa1b3f32024-04-04T04:20:15ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2024-04-011110.3389/fcvm.2024.13251691325169Extending heart preservation to 24 h with normothermic perfusionBrianna L. Spencer0Spencer K. Wilhelm1Christopher Stephan2Kristopher A. Urrea3Daniela Pelaez Palacio4Robert H. Bartlett5Daniel H. Drake6Daniel H. Drake7Alvaro Rojas-Pena8Alvaro Rojas-Pena9Extracorporeal Life Support Laboratory, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United StatesExtracorporeal Life Support Laboratory, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United StatesExtracorporeal Life Support Laboratory, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United StatesExtracorporeal Life Support Laboratory, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United StatesExtracorporeal Life Support Laboratory, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United StatesExtracorporeal Life Support Laboratory, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United StatesExtracorporeal Life Support Laboratory, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cardiac Surgery, University of Michigan Medical School, Ann Arbor, MI, United StatesExtracorporeal Life Support Laboratory, Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Surgery, Section of Transplantation, University of Michigan Medical School, Ann Arbor, MI, United StatesCold static storage (CSS) for up to 6 h is the gold standard in heart preservation. Although some hearts stored over 6 h have been transplanted, longer CSS times have increased posttransplant morbimortality. Transmedics® Organ Care System (OCS™) is the only FDA-approved commercial system that provides an alternative to CSS using normothermic ex situ heart perfusion (NEHP) in resting mode with aortic perfusion (Langendorff method). However, it is also limited to 6 h and lacks an objective assessment of cardiac function. Developing a system that can perfuse hearts under NEHP conditions for >24 h can facilitate organ rehabilitation, expansion of the donor pool, and objective functional evaluation. The Extracorporeal Life Support Laboratory at the University of Michigan has worked to prolong NEHP to >24 h with an objective assessment of heart viability during NEHP. An NEHP system was developed for aortic (Langendorff) perfusion using a blood-derived perfusate (leukocyte/thrombocyte-depleted blood). Porcine hearts (n = 42) of different sizes (6–55 kg) were divided into five groups and studied during 24 h NEHP with various interventions in three piglets (small-size) heart groups: (1) Control NEHP without interventions (n = 15); (2) NEHP + plasma exchange (n = 5); (3) NEHP + hemofiltration (n = 10) and two adult-size (juvenile pigs) heart groups (to demonstrate the support of larger hearts); (4) NEHP + hemofiltration (n = 5); and (5) NEHP with intermittent left atrial (iLA) perfusion (n = 7). All hearts with NEHP + interventions (n = 27) were successfully perfused for 24 h, whereas 14 (93.3%) control hearts failed between 10 and 21 h, and 1 control heart (6.6%) lasted 24 h. Hearts in the piglet hemofiltration and plasma exchange groups performed better than those in the control group. The larger hearts in the iLA perfusion group (n = 7) allowed for real-time heart functional assessment and remained stable throughout the 24 h of NEHP. These results demonstrate that heart preservation for 24 h is feasible with our NEHP perfusion technique. Increasing the preservation period beyond 24 h, infection control, and nutritional support all need optimization. This proves the concept that NEHP has the potential to increase the organ pool by (1) considering previously discarded hearts; (2) performing an objective assessment of heart function; (3) increasing the donor/recipient distance; and (4) developing heart-specific perfusion therapies.https://www.frontiersin.org/articles/10.3389/fcvm.2024.1325169/fullheart preservationnormothermicex situex vivoprolongedperfusion
spellingShingle Brianna L. Spencer
Spencer K. Wilhelm
Christopher Stephan
Kristopher A. Urrea
Daniela Pelaez Palacio
Robert H. Bartlett
Daniel H. Drake
Daniel H. Drake
Alvaro Rojas-Pena
Alvaro Rojas-Pena
Extending heart preservation to 24 h with normothermic perfusion
Frontiers in Cardiovascular Medicine
heart preservation
normothermic
ex situ
ex vivo
prolonged
perfusion
title Extending heart preservation to 24 h with normothermic perfusion
title_full Extending heart preservation to 24 h with normothermic perfusion
title_fullStr Extending heart preservation to 24 h with normothermic perfusion
title_full_unstemmed Extending heart preservation to 24 h with normothermic perfusion
title_short Extending heart preservation to 24 h with normothermic perfusion
title_sort extending heart preservation to 24 h with normothermic perfusion
topic heart preservation
normothermic
ex situ
ex vivo
prolonged
perfusion
url https://www.frontiersin.org/articles/10.3389/fcvm.2024.1325169/full
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