Reconditioning of circulatory death hearts by ex-vivo machine perfusion with a novel HTK-N preservation solution

Saemann, Lars; Korkmaz‐Icöz, Sevil; Hoorn, Fabio; Veres, Gábor; Kraft, Patricia; Georgevici, Adrian-Iustin; Brüne, Martin; Guo, Yuxing; Loganathan, Sivakkanan; Wenzel, Folker; Kretzler, Matthias; Szabó, Gábor

doi:10.1016/j.healun.2021.07.009

Cited by 11 publications

(12 citation statements)

References 31 publications

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“…The finding that prediction models based on 2 combined parameters are superior to 1‐variable models is consistent with the results from our previous study on normothermic blood perfusion in a porcine DCD model. 8 Therefore, this study confirms that in hypothermic, cardioplegic MP, 2 combined variables provide more predictive information about contractile function during reperfusion than 1 parameter.…”

Section: Discussionsupporting

confidence: 76%

“…This finding is already worth transferring into clinical practice. 8 Secondly, the major concern of cardioplegic preservation of DCD hearts, which is the impossibility to evaluate the heart before transplantation, could be dispelled by monitoring microvascular flow shifts during continuous cardioplegic perfusion. Besides, even during normothermic blood perfusion, the heart is evaluated based on visual inspection and lactate clearance.…”

Section: Discussionmentioning

confidence: 99%

“…Characteristics of Custodiol‐N are described elsewhere. 8 The perfusion pressure was set at 20 mm Hg. We continuously oxygenated the perfusate solution with an integrated oxygenator.…”

Section: Methodsmentioning

confidence: 99%

“…Despite the remarkable success of normothermic blood perfusion in the clinical setting, we have recently shown in a porcine model of DCD that MP with hypothermic, oxygenated, crystalloid Custodiol‐N preservation solution is superior to blood perfusion to recondition contractile function. 8 Based on these preclinical results, a translation of crystalloid MP with Custodiol‐N into clinical practice could be promising. Nevertheless, hypothermic MP with a cardioplegic preservation solution facilitates nonbeating transportation.…”

mentioning

confidence: 99%

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Prediction Model for Contractile Function of Circulatory Death Donor Hearts Based on Microvascular Flow Shifts During Ex Situ Hypothermic Cardioplegic Machine Perfusion

Saemann

Kohl

Veres

et al. 2022

JAHA

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Background Hearts procured from circulatory death donors (DCD) are predominantly maintained by machine perfusion (MP) with normothermic donor blood. Currently, DCD heart function is evaluated by lactate and visual inspection. We have shown that MP with the cardioplegic, crystalloid Custodiol‐N solution is superior to blood perfusion to maintain porcine DCD hearts. However, no method has been developed yet to predict the contractility of DCD hearts after cardioplegic MP. We hypothesize that the shift of microvascular flow during continuous MP with a cardioplegic preservation solution predicts the contractility of DCD hearts. Methods and Results In a pig model, DCD hearts were harvested and maintained by MP with hypothermic, oxygenated Custodiol‐N for 4 hours while myocardial microvascular flow was measured by Laser Doppler Flow (LDF) technology. Subsequently, hearts were perfused with blood for 2 hours, and left ventricular contractility was measured after 30 and 120 minutes. Various novel parameters which represent the LDF shift were computed. We used 2 combined LDF shift parameters to identify bivariate prediction models. Using the new prediction models based on LDF shifts, highest r 2 for end‐systolic pressure was 0.77 ( P =0.027), for maximal slope of pressure increment was 0.73 ( P =0.037), and for maximal slope of pressure decrement was 0.75 ( P =0.032) after 30 minutes of reperfusion. After 120 minutes of reperfusion, highest r 2 for end‐systolic pressure was 0.81 ( P =0.016), for maximal slope of pressure increment was 0.90 ( P =0.004), and for maximal slope of pressure decrement was 0.58 ( P =0.115). Identical prediction models were identified for maximal slope of pressure increment and for maximal slope of pressure decrement at both time points. Lactate remained constant and therefore was unsuitable for prediction. Conclusions Contractility of DCD hearts after continuous MP with a cardioplegic preservation solution can be predicted by the shift of LDF during MP.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

“…Characteristics of Custodiol‐N are described elsewhere. 8 The perfusion pressure was set at 20 mm Hg. We continuously oxygenated the perfusate solution with an integrated oxygenator.…”

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Prediction Model for Contractile Function of Circulatory Death Donor Hearts Based on Microvascular Flow Shifts During Ex Situ Hypothermic Cardioplegic Machine Perfusion

Saemann

Kohl

Veres

et al. 2022

JAHA

Self Cite

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“…First, adenosine is an essential component of the University of Wisconsin solution (UW) and Institut Georges Lopez-1 (IGL-1) preservation solutions. Researchers have reported that the adenosine-containing Histidine-tryptophan-ketoglutarate (HTK) preservation solution has a better protective effect on myocardium than the standard HTK preservation solution, which prevents myocardial cell swelling and necrosis by reducing oxidative and nitrosative stress ( 147 ). Pre-treatment with adenosine prolongs donor heart storage and protects heart grafts from IRI ( 148 , 149 ).…”

Section: Clinical Application and Prospectsmentioning

confidence: 99%

The Role of Purinergic Signaling in Heart Transplantation

et al. 2022

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Heart transplantation remains the optimal treatment option for patients with end-stage heart disease. Growing evidence demonstrates that purinergic signals mediated by purine nucleotides and nucleosides play vital roles in heart transplantation, especially in the era of ischemia-reperfusion injury (IRI) and allograft rejection. Purinergic signaling consists of extracellular nucleotides and nucleosides, ecto-enzymes, and cell surface receptors; it participates in the regulation of many physiological and pathological processes. During transplantation, excess adenosine triphosphate (ATP) levels are released from damaged cells, and driver detrimental inflammatory responses largely via purinergic P2 receptors. Ecto-nucleosidases sequentially dephosphorylate extracellular ATP to ADP, AMP, and finally adenosine. Adenosine exerts a cardioprotective effect by its anti-inflammatory, antiplatelet, and vasodilation properties. This review focused on the role of purinergic signaling in IRI and rejection after heart transplantation, as well as the clinical applications and prospects of purinergic signaling.

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Modern concepts of cardioplegia

Saemann,

Szabó

2024

Z Herz- Thorax- Gefäßchir

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Reconditioning of circulatory death hearts by ex-vivo machine perfusion with a novel HTK-N preservation solution

Cited by 11 publications

References 31 publications

Prediction Model for Contractile Function of Circulatory Death Donor Hearts Based on Microvascular Flow Shifts During Ex Situ Hypothermic Cardioplegic Machine Perfusion

Prediction Model for Contractile Function of Circulatory Death Donor Hearts Based on Microvascular Flow Shifts During Ex Situ Hypothermic Cardioplegic Machine Perfusion

The Role of Purinergic Signaling in Heart Transplantation

Modern concepts of cardioplegia

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