HTK-N Versus Del Nido Cardioplegia for Hypothermic Machine Perfusion of Donation after Circulatory Death Hearts: Comparison of Left-Ventricular Contractility and Transcriptomics
Abstract
Purpose
Del Nido cardioplegia (dNC) is a 1:4 formula of blood:crystalloid and contains erythrocytes as oxygen carriers. Hearts donated after circulatory death (DCD) are maintained by ex-vivo machine perfusion (EVMP) with blood. Nevertheless, we already showed in a porcine model that EVMP with crystalloid histidine-tryptophane-ketoglutarate-N (HTK-N) is superior to blood to preserve left-ventricular (LV) contractility. However, the effect of EVMP with dNC on contractility and myocardial microcirculation of DCD hearts is unkown.
Methods
In a pig model of DCD, hearts were harvested and maintained for 4 h by EVMP with hypothermic, oxygenated HTK-N (DCD-HTK-N) or dNC (DCD-dNC) followed by reperfusion with blood for 2 h including assessment of LV contractility and myocardial microvascular flow with a Laser-Doppler-Flow (LDF) probe. In a DCD group, hearts underwent reperfusion including functional evaluation immediately after procurement. In a Control group, no circulatory death was induced (all groups N=8). We performed transcriptomics for LV myocardial samples using gene microarrays (25,470 genes).
Results
In DCD-HTK-N, the end-systolic pressure (ESP; Control: 188±10 mmHg, DCD: 136±9 mmHg, DCD-HTK-N: 165±7 mmHg/s, DCD-dNC: 120±5 mmHg/s; p<0.05), maximal slope of pressure increment (dp/dtmax; Ctrl: 1925±203 mmHg/s, DCD: 1196±257 mmHg/s, DCD-HTK-N: 2291±261 mmHg/s, DCD-dNC: 943±88 mmHg/s; p<0.05) and of pressure decrement (dp/dtmin; Ctrl: -1060±94 mmHg/s, DCD: -730±78 mmHg/s, DCD-HTK-N: -1037±168 mmHg/s, DCD-dNC: -571±51 mmHg/s) was superior in DCD-HTK-N. Relative LDP was higher in DCD-HTK-N compared to DCD-dNC (1.46±0.1 vs. 1.27±0.9). In DCD-HTK-N, 52 genes were up-, and 188 were downregulated; in DCD-dNC, 6 were up-, and 109 were downregulated, both compared to DCD. In DCD-dNC compared to DCD-HTK-N, 16 genes were up- (involved in platelet adhesion and arteriosclerosis), and 25 genes were downregulated (involved in TNFR1-induced proapoptotic and NFkB signaling).
Conclusion
In EVMP of porcine DCD hearts with hypothermic preservation solutions, compared to dNC, HTK-N is superior to dNC for preserving the systolic and diastolic function, improving myocardial microcirculation and mediating the upregulation of protective and downregulation of apoptotic pathways.