Monitoring of perfusion quality and prediction of donor heart function during ex-vivo machine perfusion by myocardial microcirculation versus surrogate parameters

Saemann, Lars; Wenzel, Folker; Kohl, Matthias; Korkmaz‐Icöz, Sevil; Hoorn, Fabio; Loganathan, Sivakkanan; Guo, Yuxing; Ding, Qingwei; Zhou, Pengyu; Veres, Gábor; Kretzler, Matthias; Szabó, Gábor

doi:10.1016/j.healun.2021.02.013

Cited by 13 publications

(11 citation statements)

References 10 publications

(6 reference statements)

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“…According to a previously published model, we induced circulatory death through the termination of mechanical ventilation [ 7 ]. Within the subsequent period of 30 min, we collected blood and harvested the heart.…”

Section: Methodsmentioning

confidence: 99%

Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction

et al. 2022

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Microvascular dysfunction (MVD) in cardiac allografts is associated with an impaired endothelial function in the coronary microvasculature. Ischemia/reperfusion injury (IRI) deteriorates endothelial function. Hearts donated after circulatory death (DCD) are exposed to warm ischemia before initiating ex vivo blood perfusion (BP). The impact of cytokine adsorption during BP to prevent MVD in DCD hearts is unknown. In a porcine DCD model, we assessed the microvascular function of hearts after BP with (DCD-BPCytoS, n = 5) or without (DCD-BP, n = 5) cytokine adsorption (CytoSorb®). Microvascular autoregulation was assessed by increasing the coronary perfusion pressure, while myocardial microcirculation was measured by Laser-Doppler-Perfusion (LDP). We analyzed the immunoreactivity of arteriolar oxidative stress markers nitrotyrosine and 4-hydroxy-2-nonenal (HNE), endothelial injury indicating cell adhesion molecules CD54, CD106 and CD31, and eNOS. We profiled the concentration of 13 cytokines in the perfusate. The expression of 84 genes was determined and analyzed using machine learning and decision trees. Non-DCD hearts served as a control for the gene expression analysis. Compared to DCD-BP, relative LDP was improved in the DCD-BPCytoS group (1.51 ± 0.17 vs. 1.08 ± 0.17). Several pro- and anti-inflammatory cytokines were reduced in the DCD-BPCytoS group. The expression of eNOS significantly increased, and the expression of nitrotyrosine, HNE, CD54, CD106, and CD31, markers of endothelial injury, majorly decreased in the DCD-BPCytoS group. Three genes allowed exact differentiation between groups; regulation of HIF1A enabled differentiation between perfusion (DCD-BP, DCD-BPCytoS) and non-perfusion groups. CAV1 allowed differentiation between BP and BPCytoS. The use of a cytokine adsorption device during BP counteracts preload-dependent MVD and preserves the microvascular endothelium by preventing oxidative stress and IRI of coronary arterioles of DCD hearts.

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Section: Methodsmentioning

confidence: 99%

Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction

et al. 2022

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“…According to a previously published model, we induced circulatory death by the termination of mechanical ventilation. 9 Within the subsequent period of 30 minutes, blood was collected in blood collection bags and the heart was harvested. After a total warm ischemic period of 30 minutes, the DCD hearts were flushed with 2 L of cold (4°C) traditional Custodiol preservation solution (Köhler Chemie GmbH, Bensheim, Germany) followed by mounting on the perfusion system (Figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

“…Various novel parameters Were calculated that reflect the shift of microvascular flow during hypothermic, cardioplegic MP based on our already published equations shown in Table S1 . 9 In brief, the LDP signal needs to be analyzed in periods to incorporate periodic variations no matter the LDP at a particular time point or over a time frame is of interest (Figure 2A ). 11 We either expressed LDP as a “singular” measurement (mean over 20 seconds) periodically every 30 minutes or as an “interval” measurement (mean over 30 minutes).…”

Section: Methodsmentioning

confidence: 99%

“…The use of 2 combined parameters is based on the findings from a previous study, which showed that the combination of 2 parameters could incorporate more predictive power. 9 …”

Section: Methodsmentioning

confidence: 99%

“…Based on changes of myocardial microcirculation during normothermic MP, the new prediction model is based on microvascular flow shifts during hypothermic MP. 9 …”

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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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Monitoring of myocardial microcirculation during machine perfusion of donor hearts for prediction of contractility

Saemann

Wenzel

Simm

et al. 2023

Z Herz- Thorax- Gefäßchir

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Monitoring of perfusion quality and prediction of donor heart function during ex-vivo machine perfusion by myocardial microcirculation versus surrogate parameters

Cited by 13 publications

References 10 publications

Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction

Cytokine Adsorber Use during DCD Heart Perfusion Counteracts Coronary Microvascular Dysfunction

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

Monitoring of myocardial microcirculation during machine perfusion of donor hearts for prediction of contractility

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