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. 2023 Jul 17;24(14):11562.
doi: 10.3390/ijms241411562.

Improving Diastolic and Microvascular Function in Heart Transplantation with Donation after Circulatory Death

Lars Saemann  1   2 , Adrian-Iustin Georgevici  1   3 , Fabio Hoorn  2   4 , Nitin Gharpure  1 , Gábor Veres  1   2 , Sevil Korkmaz-Icöz  1   2 , Matthias Karck  2 , Andreas Simm  1 , Folker Wenzel  4 , Gábor Szabó  1   2
Affiliations

Improving Diastolic and Microvascular Function in Heart Transplantation with Donation after Circulatory Death

Lars Saemann et al. Int J Mol Sci. .

Abstract

The impact of the machine perfusion of donation after circulatory death (DCD) hearts with the novel Custodiol-N solution on diastolic and coronary microvascular dysfunction is unknown. Porcine DCD-hearts were maintained four hours by perfusion with normothermic blood (DCD-B), hypothermic Custodiol (DCD-C), or Custodiol-N (DCD-CN), followed by one hour of reperfusion with fresh blood, including microvascular and contractile evaluation. In another group (DCD group), one hour of reperfusion, including microvascular and contractile evaluation, was performed without a previous maintenance period (all groups N = 5). We measured diastolic function with a balloon catheter and microvascular perfusion by Laser-Doppler-Technology, resulting in Laser-Doppler-Perfusion (LDP). We performed immunohistochemical staining and gene expression analysis. The developed pressure was improved in DCD-C and DCD-CN. The diastolic pressure decrement (DCD-C: -1093 ± 97 mmHg/s; DCD-CN: -1703 ± 329 mmHg/s; DCD-B: -690 ± 97 mmHg/s; p < 0.05) and relative LDP (DCD-CN: 1.42 ± 0.12; DCD-C: 1.11 ± 0.13; DCD-B: 1.22 ± 0.27) were improved only in DCD-CN. In DCD-CN, the expression of eNOS increased, and ICAM and VCAM decreased. Only in DCD-B compared to DCD, the pathways involved in complement and coagulation cascades, focal adhesion, fluid shear stress, and the IL-6 and IL-17 pathways were upregulated. In conclusion, machine perfusion with Custodiol-N improves diastolic and microvascular function and preserves the microvascular endothelium of porcine DCD-hearts.

Keywords: Custodiol-N; HTK-N; Laser-Doppler-Flow; Laser-Doppler-Perfusion; donation after circulatory death; heart transplantation; machine learning; machine perfusion; microcirculation; microvascular dysfunction.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Systolic and diastolic function. * p < 0.05 compared to DCD and # p < 0.05 compared to DCD-B. B: Blood. DCD: Donation after circulatory death. C: Custodiol. CN: Custodiol-N. LVV: Left-ventricular volume.
Figure 2
Figure 2
Coronary macro- and microvascular function. (A,B) Myocardial microcirculation in dependence of different CPP. (C,D) Total coronary flow in dependence of different CPP. # p < 0.05 compared to Control. * p < 0.05, ** p < 0.001, and *1 p = 0.065 compared to DCD. B: Blood. DCD: Donation after circulatory death. CPP: Coronary perfusion pressure. C: Custodiol. CN: Custodiol-N.
Figure 3
Figure 3
Coronary microvascular function. *1 p = 0.059, *2 p = 0.062, and *3 p = 0.056 compared to DCD-B. DCD: Donation after circulatory death. C: Custodiol. CN: Custodiol-N. B: Blood. LVV: Left-ventricular volume.
Figure 4
Figure 4
Coronary elasticity and compliance. # p < 0.05 compared to Control. * p < 0.05, *1 p = 0.066, and *2 p = 0.052 compared to DCD. DCD: Donation after circulatory death. C: Custodiol. CN: Custodiol-N. B: Blood.
Figure 5
Figure 5
Immunoreactivity of cell adhesion molecules. (A–D) Representative photomicrographs are shown. (E–H) Semiquantitative scoring. B: Blood. C: Custodiol. CN: Custodiol-N. DCD: Donation after circulatory death. eNOS: Endothelial nitric oxide synthase. ICAM: Intracellular cell adhesion molecule-1. VCAM: Vascular cell adhesion molecule-1. PECAM: platelet endothelial cell adhesion molecule-1. * p < 0.05 vs. DCD. # p < 0.05 vs. DCD-B.
Figure 6
Figure 6
Gene expression. (A) For construction of the heatmap, a median linkage using Kendall’s tau was applied. (B) For the volcano plot comparison, a t-test with Bonferroni correction was applied. B: Blood. C: Custodiol. CN: Custodiol-N. DCD: Donation after circulatory death.
Figure 7
Figure 7
Pathway analysis of gene expression. For construction of the heatmap, median linkage using Kendall’s tau was applied. B: Blood. C: Custodiol. CN: Custodiol-N. DCD: Donation after circulatory death.
Figure 8
Figure 8
Study Groups. CD: Circulatory Death. DCD: Donation after circulatory death. C: Custodiol. CN: Custodiol-N. B: Blood.
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