Table 2.
Other major therapeutic additives in models of ex vivo liver machine perfusion
| Ref. | Ex vivo perfusion type | Therapeutic | Problem | Animal | Model | Sample size | Ex vivo perfusion time (h) | Outcomes |
| Goldaracena et al[9], 2016 | SNMP | Anti-inflammatory agents | IRI | Pig | Transplantation | 5 | 4 | During EVLP: lower AST, TNF-α, IL-6 |
| Lower HA levels, β-galactosidase and higher IL-10 (nonsignificant) | ||||||||
| After transplantation: Lower bilirubin, lower IL-6, lower cleaved caspase 3 staining, intact sinusoidal endothelial cell lining | ||||||||
| (Alprostadil, n-acetylcysteine, carbon monoxide, sevoflurane) | ||||||||
| Lower AST, TNF-α, HA, | ||||||||
| ALP and higher IL-10 (nonsignificant) | ||||||||
| Rigo et al[65], 2018 | NMP | HLSC-EV | IRI | Rat | EVLP | 9 | 4 | HLSC-EV uptake in treated livers |
| Reduced necrosis and apoptosis on histology, lower Suzuki tissue injury score, lower apoptosis, lower AST and LDH, lower HIF-1α & TGF-β1 (hypoxia induced markers) | ||||||||
| NMP had low hematocrit to induce hypoxia | ||||||||
| Beal et al[66], 2019 | NMP | Enkephalin | IRI | Rat | EVLP | 6 | 4 | 10 μmol/L determined to be optimal concentration in an in vitro model: Lower ALT and MDA; better preservation of structural architecture; decreased caspase-3 expression; |
| (δ-opioid agonist) | ||||||||
| decreased TUNEL staining; decreased phosphorylation of p38 and JNK; increased expression of p-Akt, PI3K, p-Bad and Bcl-2 | ||||||||
| Yu et al[67], 2019 | HMP | NLRP3 Inflammasome | IRI | Pig | Transplantation | 6 | 2 | All reduced in HMP-postop group with added mcc950 in perfusate and IV administration of mcc950 |
| After transplantation: TNF-α, IL-1β, β-galactosidase, post-reperfusion serum ALT and AST, MDA, apoptosis staining, caspase-1 levels | ||||||||
| Inhibitor mcc950 | ||||||||
SNMP: Subnormothermic machine perfusion; NMP: Normothermic machine perfusion; HMP: Hypothermic machine perfusion; IRI: Ischemia-reperfusion injury; EVLP: Ex vivo liver perfusion; AST: Aspartate aminotransferase; HA: Hyaluronic acid; ALP: Alkaline phosphatase; HLSC-EV: Human liver stem cells-derived extracellular vesicles; LDH: Lactate dehydrogenase; ALT: Alanine aminotransferase; MDA: Malondialdehyde; IV: Intravenous.