Preservation solution Custodiol containing human alpha-1-antitrypsin improves graft recovery after prolonged cold ischemic storage in a rat model of heart transplantation

Figures

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  Figure 1. Effect of alpha-1-antitrypsin (AAT) on left-ventricular systolic and diastolic function in grafts after prolonged ischemia. (A) LV systolic pressure (LVSP), (B) developed pressure, (C) maximal slope of systolic pressure increment (dP/dtmax), (D) rate pressure product, and (E) maximal slope of diastolic pressure decrement (dP/dtmin). Values are presented as mean ± SEM. *p < 0.05 vs. 1h ischemia, # p < 0.05 vs. 1h ischemia+AAT, $ p < 0.05 vs. 5h ischemia. n=7-9 rats/group.

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  Figure 2. Effect of alpha-1-antitrypsin (AAT) on neutrophil infiltration in grafts after prolonged ischemia. Representative images of myeloperoxidase immunohistochemical staining (MPO, x200 magnification, scale bar: 100 µm), followed by quantification of MPO-positive cells. Values are presented as mean ± SEM. *p < 0.05 vs. 1h ischemia, # p < 0.05 vs. 1h ischemia+AAT, $ p < 0.05 vs. 5h ischemia. n=6-8 rats/group.

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  Figure 3. Machine learning-based Boruta networks of gene-gene interactions per study arm. Gene correlation network (A) Ischemia groups and (B) alpha-1-antitrypsin (AAT) groups. Each gene investigated is represented by a node, with the closeness between nodes and the connection width being proportional to the random-forest variable importance. Spearman’s coefficients are indicated by color, with blue or red lines representing positive or negative correlations, respectively. Connections colored in grey represent random-forest patterns that do not show a significant Spearman coefficient. Refer to Online Table 1 for gene abbreviations. AAT indicates alpha-1-antitrypsin.

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  Figure 4. Myocardial gene expression analyzed using modern statistical and machine learning algorithms. The decision tree C5.0 display the splitting criteria employed in the inter-group classification. 1) if Flt1 expression is ≤ 23.029 and Gpx3 expression is ≤ 20.448, the cardiac graft belongs to either the 1h ischemia (1h IR) or 5h ischemia (5h IR) groups. If Flt1 expression is ≤ 23.029 and Gpx3 expression is > 20.448, the graft belongs to the 5h ischemia + AAT (5h IR+AAT) group. 2) If Flt1 expression is > 23.029 and Cflar expression ≤ 21.651, the graft belongs to the 5h ischemia (5h IR) group. If Flt1 expression is > 23.029 and Cflar expression > 21.651 and Bcl2 ≤ 21.798, the graft belongs to either the 1h ischemia (1h IR) or 5h ischemia (5h IR) or 5h ischemia + AAT (5h IR+AAT) groups. If Flt1 expression is > 23.029 and Cflar expression > 21.651 and Bcl2 > 21.798, the graft belongs to either the 1h ischemia (1h IR) or 5h ischemia + AAT (5h IR+AAT) groups. Refer to Online Table 1 for gene abbreviations. AAT indicates alpha-1-antitrypsin, IR ischemia/reperfusion.