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Letters to the Editor

Hypothermic Ex Vivo Perfusion: Protecting the Donor Heart and the Recipient

See Hoe, Louise E.*,†; Suen, Jacky Y.*,†; Li Bassi, Gianluigi*,†,‡; McGiffin, David C.*,§; Fraser, John F.*,†

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doi: 10.1097/MAT.0000000000001102
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To the Editor:

We congratulate McLeod et al1 on their study demonstrating successful preservation of hearts for 72 hours utilizing normothermic ex vivo perfusion (NEVP) and plasma cross-circulation, using a live para-corporeal donor sheep. This is a great achievement, because heart preservation was well beyond current clinical storage time limits. However, although the authors note future plans to simplify, the preservation method could be considered methodologically challenging. Additionally, the clinical relevance is somewhat difficult to determine, because of the absence of donor brain death (BD) and related sequelae, well reported to impair organ function.

The global crisis of insufficient donor hearts available to meet the increasing demand of end-stage heart failure patients has fostered great scientific creativity and expansion of a research field rapidly trying to find a solution. McLeod et al focused primarily on NEVP, a preservation method currently used clinically with the Transmedics Organ Care system for donor hearts. Interestingly, growing evidence of hypothermic ex vivo perfusion (HEVP) using novel technology may become an alternative for donor heart preservation. Steen et al2 reported that following 24 hours BD in a pig model, donor hearts can be preserved for 24 hours utilizing HEVP and transplanted into recipients and can remain viable up to 24 hours post transplant. Intriguingly, the solution utilized for this HEVP system is a hyperoncotic cardioplegia solution, supplemented with packed red blood cells as the oxygen carrier, which McLeod et al suggested is the optimal oxygen carrier.1,3,4 Indeed, although it remains to be elucidated, perhaps there are similarities in the beneficial outcomes of these two studies, where both plasma cross-circulation and the HEVP hyperoncotic solution contain significant albumin in the perfusate, likely assisting with limiting myocardial edema over extended preservation times.1,2 Initial outcomes of the safety study utilizing this HEVP technology and perfusate solution in humans appear promising, with evidence of reduced markers of cardiac injury post transplant.5

An important component missing from the study by McLeod et al is the impact of donor BD upon the donor heart. Brain death undoubtedly impairs donor heart function6 and vasomotor tone both in the donor and, potentially, in the recipient. Interestingly, McLeod et al emphasized that “there might be something in plasma which prevents capillary leakage.”1 The Critical Care Research Group has developed a sheep model of 24 hours donor BD followed by heart transplantation (HTx).7 In collaboration with Professor Steen, we have employed his technology in our sheep model of BD-HTx, to examine the impact of 8 hours HEVP upon posttransplant outcomes. The 8-hour preservation period (time donor heart spends in HEVP machine) is a critical time for Australian HTx settings, when distance between transplant centers is problematic. Our preliminary results are promising, suggesting that HEVP could be beneficial both to the recovery of the transplanted heart and preservation of the recipient vasomotor tone.

Hopefully, with the development of several novel technologies and substantial preclinical studies to support human trials, we can be optimistic about the future of HTx, and many viable options of heart preservation technology will be available for all clinical situations.

References

1. McLeod JS, Poling C, Church JT, et al. Ex vivo heart perfusion for 72 hours using plasma cross circulation. ASAIO J 2020; 66:753–759.
2. Steen S, Paskevicius A, Liao Q, Sjoberg T. Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours. Scand Cardiovasc J 2016; 50:193–200.
3. Church JT, Alghanem F, Deatrick KB, et al. Normothermic Ex Vivo heart perfusion: Effects of live animal blood and plasma cross circulation. ASAIO J 2017; 63:766–773.
4. Trahanas JM, Witer LJ, Alghanem F, et al. Achieving 12 hour normothermic Ex Situ heart perfusion: An experience of 40 porcine hearts. ASAIO J 2016; 62:470–476.
5. Nilsson J, Jernryd V, Qin G, et al. Non ischemic heart preservation — results from the Safety Study. J Heart Lung Transplant 2019; 38:S26.
6. Apostolakis E, Parissis H, Dougenis D. Brain death and donor heart dysfunction: Implications in cardiac transplantation. J Card Surg 2010; 25:98–106.
7. See Hoe L, Engkilde-Pedersen S, Obonyo N, et al. Development of an ovine model of heart transplantation following 24-hour brain stem death. Heart Lung Circ 2018; 27:S92.
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