Hypothermic continuous machine perfusion enables preservation of energy charge and functional recovery of heart grafts in an<i>ex vivo</i>model of donation following circulatory death

Caenegem, Olivier Van; Beauloye, Christophe; Bertrand, Luc; Horman, Sandrine; Lepropre, Sophie; Sparavier, Grégory; Vercruysse, Jonathan; Bethuyne, Noëlla; Poncelet, Alain; Gianello, Pierre; Demuylder, Peter; Legrand, E; Beaurin, Gwen; Bontemps, Françoise; Jacquet, Luc‐Marie; Vanoverschelde, Jean–Louis

doi:10.1093/ejcts/ezv409

Cited by 42 publications

(33 citation statements)

References 25 publications

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“…13,14 Thus we did not rapidly rewarm the heart, instead allowing the circuit to warm to goal temperature during the first hour. Perfusion began at a pressure of 20 mmHg and at 20°C, and was increased slowly over the hour to the goal of 40–60 mmHg, and 37°C.…”

Section: Methodsmentioning

confidence: 99%

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts

Trahanas¹,

Witer

Alghanem

et al. 2016

ASAIO Journal

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Although total body perfusion with extracorporeal life support (ECLS) can be maintained for weeks, individual organ perfusion beyond 12 hours has yet to be achieved clinically. Normothermic ex situ heart perfusion (ESHP) offers the potential for prolonged cardiac preservation. We developed an ESHP system to study the effect of perfusate variables on organ preservation, with the ultimate goal of extending organ perfusion for ≥ 24 hours. Forty porcine hearts were perfused for a target of 12 hours. Hearts that maintained electromechanical activity and had a <3× increase in vascular resistance were considered successful preservations. Perfusion variables, metabolic byproducts, and histopathology were monitored and sampled to identify factors associated with preservation failure. Twenty-two of 40 hearts were successfully preserved at 12 hours. Successful 12-hour experiments demonstrated lower potassium (4.3±0.8 vs. 5.0±1.2 mmol/L, p=0.018) and lactate (3.5±2.8 vs. 4.5±2.9 mmol/L, p=0.139) levels, and histopathology revealed less tissue damage (p=0.003) and less weight gain (p=0.072). Results of these early experiments suggest prolonged ESHP is feasible, and that elevated lactate and potassium levels are associated with organ failure. Further studies are necessary to identify the ideal perfusate for normothermic ESHP.

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Section: Methodsmentioning

confidence: 99%

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts

Trahanas¹,

Witer

Alghanem

et al. 2016

ASAIO Journal

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“…HMP improved the preservation of DCD heart grafts compared to SCS proven by superior postreperfusion contractility. The underlying mechanisms could include enhanced preservation of the energetic states and superior cellular integrity (87). Recently, Korkmaz-Icöz et al (88) demonstrated that HMP of aged donor hearts with MSCs protected against myocardial IRI in a rat model.…”

Section: Machine Perfusion Of Extended Criteria Donor Heart Graftsmentioning

confidence: 99%

Machine Perfusion of Extended Criteria Donor Organs: Immunological Aspects

et al. 2020

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Due to higher vulnerability and immunogenicity of extended criteria donor (ECD) organs used for organ transplantation (Tx), the discovery of new treatment strategies, involving tissue allorecognition pathways, is important. The implementation of machine perfusion (MP) led to improved estimation of the organ quality and introduced the possibility to achieve graft reconditioning prior to Tx. A significant number of experimental and clinical trials demonstrated increasing support for MP as a promising method of ECD organ preservation compared to classical static cold storage. MP reduced ischemia-reperfusion injury resulting in the protection from inadequate activation of innate immunity. However, there are no general agreements on MP protocols, and clinical application is limited. The objective of this comprehensive review is to summarize literature on immunological effects of MP of ECD organs based on experimental studies and clinical trials.

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“…Continuous perfusion flushes the organ of toxic metabolites and accumulated acids within the dilutional and buffering capacity of the preservation solution. The graft does not become truly ischemic and thus limits oxidative stresses and free radical mediated cellular damage associated with reperfusion injury . Perfusion devices also tightly regulate perfusate temperature, eliminating the detrimental effects of uncontrolled profound hypothermia.…”

Section: Potential Benefits and Limitations Of Machine Perfusion Presmentioning

confidence: 99%

“…The graft does not become truly ischemic and thus limits oxidative stresses and free radical mediated cellular damage associated with reperfusion injury. 24,[28][29][30][31] Perfusion devices also tightly regulate perfusate temperature, eliminating the detrimental effects of uncontrolled profound hypothermia. Additionally, cardiac allografts can be "conditioned" prior to transplantation by addition of therapeutic drugs, cytokines, gene products, or other agents.…”

Section: And Limitations Of Machine Perfusion Preservation Of Donor Hmentioning

confidence: 99%

Ice, ice, maybe? Is it time to ditch the igloo cooler? Benefits of machine perfusion preservation of donor hearts

Jessen

Peltz

2019

Artificial Organs

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Hypothermic continuous machine perfusion enables preservation of energy charge and functional recovery of heart grafts in anex vivomodel of donation following circulatory death

Abstract: MP preservation of DCD hearts results in improved preservation of the energy and improved functional recovery of heart grafts compared with CS.

Cited by 42 publications

References 25 publications

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts

Machine Perfusion of Extended Criteria Donor Organs: Immunological Aspects

Ice, ice, maybe? Is it time to ditch the igloo cooler? Benefits of machine perfusion preservation of donor hearts

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