Table 1.
Metabolomics in heart preservation for Tx.
| Authors | Model | Metabolomics | Results |
|---|---|---|---|
| Animal studies | |||
| Peltz et al., 2005 [28] | SCS vs. HMP with UW vs. Celsior solution (200 min) followed by 2 h reperfusion; Rats DBD without Tx; N = 10/group |
1H and 13C NMR spectroscopy; Metabolites from tissue |
200 min of SCS vs. HMP HMP: ↑ ATP, ~ADP, ↓ AMP, ~total adenylates; HMP with UW vs. Celsior Celsior: ↑ ATP, ↑ ADP, ↑ AMP, ↑ total adenylates; SCS in UW vs. Celsior: ~lactate, ~alanine |
| Rosenbaum et al., 2007 [29] | SCS vs. HMP (4 h) followed by 6 h reperfusion; Canine DBD with Tx; N = 6/group |
1H and 13C NMR spectroscopy; Metabolites from perfusate and tissue |
4 h of SCS vs. HMP HMP: ~glutamate enrichment, ↓ lactate, ↓ lactate/alanine ratio |
| Rosenbaum et al., 2008 [30] | SCS vs. HMP (4 h) followed by 6 h reperfusion; Porcine DBD with Tx; N = 4/group |
1H and 13C NMR spectroscopy; Metabolites from perfusate and tissue |
4 h of SCS vs. HMP HMP: ~glutamate enrichment, ↓ lactate, ↓ lactate/alanine ratio |
| Cobert et al., 2010 [31] | HMP with UW vs. Celsior® solution (10 h); Canine DBD without Tx; N = 8 |
1H NMR spectroscopy; Metabolites from perfusate and tissue |
10 h of HMP with UW vs. Celsior®: ~lactate, ~lactate/alanine ratio |
| Cobert et al., 2011 [32] | Retrograde HMP with different flow rates (20 min); Canine DBD without Tx; N = 6 |
1H NMR spectroscopy; Metabolites from tissue |
Lactate/alanine ratio Left atrium: > 3 Right ventricle: >2 Left ventricle: ~1 |
| Cobert et al., 2012 [33] | HMP with UW ± 13C labeled glucose vs. pyruvate (6 h); Rats DBD without Tx; N = 4/group |
1H and 13C NMR spectroscopy; Metabolites from tissue |
HMP with UW (glucose vs. pyruvate) Glucose: ↑ lactate/alanine ratio, ↓ lactate enrichment, ↓ alanine enrichment, ↓ glutamate enrichment |
| Human studies | |||
| Cobert et al., 2014 [34] | SCS vs. antegrade HMP vs. retrograde HMP (12 h); DBD without Tx; N = 7–10/group |
1H and 31P NMR spectroscopy; Metabolites from tissue |
SCS vs. HMP HMP: ↓ lactate/alanine ratio, ↑ phosphocreatine/inorganic phosphate ratio, ↑ γ-ATP/inorganic phosphate ratio, ↑ phosphocreatine/γ-ATP ratio; Antegrade vs. retrograde HMP: ~lactate/alanine ratio, ~phosphocreatine/inorganic phosphate ratio, ~γ-ATP/inorganic phosphate ratio, ~phosphocreatine/γ-ATP ratio |
| Martin et al., 2019 [35] | WI and CI (6–480 min); Mice DBD with Tx, porcine and human DBD without Tx; N = >3/group |
LC-MS; Over 100 metabolites from tissue |
30 min of WI vs. CI WI: ↑ succinate, ↑ guanine, ↑ uracil, ↑ cystidine, ↑ guanosine, ↑ proprionylcarnitine, ↑ butyryl carnitine, ↑ hypoxanthine, ↑ lactate, ↓ aconitate, ↓ ATP/ADP ratio, ↓ glycogen; 0→60 min of WI vs. CI WI: ↑ succinate, ↑ succinate/fumarate ratio; CI: ~succinate, ~succinate/fumarate ratio |
ADP, adenosine diphosphate; AMP, adenosine monophosphate; ATP, adenosine triphosphate; CI, cold ischemia; DBD, donation after brain death; HMP, hypothermic machine perfusion; LC-MS, liquid chromatography–mass spectrometry; NMR, nuclear magnetic resonance; SCS, static cold storage; Tx, transplantation; UW, University of Wisconsin solution; WI, warm ischemia.