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. 2012 May 9;1(1):6.
doi: 10.1186/2047-1440-1-6.

A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation

Tim A Berendsen  1 , Bote G Bruinsma, Jungwoo Lee, Vincent D'Andrea, Qiang Liu, Maria-Louisa Izamis, Korkut Uygun, Martin L Yarmush
Affiliations

A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation

Tim A Berendsen et al. Transplant Res. .

Abstract

Background: Liver donor shortages stimulate the development of strategies that incorporate damaged organs into the donor pool. Herein we present a simplified machine perfusion system without the need for oxygen carriers or temperature control, which we validated in a model of orthotopic liver transplantation.

Methods: Rat livers were procured and subnormothermically perfused with supplemented Williams E medium for 3 hours, then transplanted into healthy recipients (Fresh-SNMP group). Outcome was compared with static cold stored organs (UW-Control group). In addition, a rat liver model of donation after cardiac death was adapted using a 60-minute warm ischemic period, after which the grafts were either transplanted directly (WI group) or subnormothermically perfused and transplanted (WI-SNMP group).

Results: One-month survival was 100% in the Fresh-SNMP and UW-Control groups, 83.3% in the WI-SNMP group and 0% in the WI group. Clinical parameters, postoperative blood work and histology did not differ significantly between survivors.

Conclusion: This work demonstrates for the first time in an orthotopic transplantation model that ischemically damaged livers can be regenerated effectively using practical subnormothermic machine perfusion without oxygen carriers.

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Figures

Figure 1
Figure 1
Schematic of the subnormothermic machine perfusion system.
Figure 2
Figure 2
Follow-up of recipients posttransplantation.(A) Survival rates of subnormothermically perfused fresh and warm ischemic (WI) livers, as well as the simple cold storage (SCS) control group and the nonperfused WI group. (B) Body weights are normalized to preoperative weights. Error bars = SD. *P < 0.05 between WI-SNMP and UW-Control groups. **P < 0.05 between WI-SNMP and both the Fresh-SNMP and UW-Control groups.
Figure 3
Figure 3
Hepatic resistance (portal pressure/flow rate) during subnormothermic machine perfusion (SNMP) of fresh and warm ischemic groups. Each line indicates a separate SNMP experiment (n = 6 per group).
Figure 4
Figure 4
ATP analysis of fresh, warm ischemic and subnormothermically perfused livers. Error bars = 95% CI.
Figure 5
Figure 5
Parameters studied during subnormothermic machine perfusion of fresh and warm ischemic livers. Subnormothermic machine perfusion of fresh and warm ischemic (WI) livers showing levels of alanine aminotransferase (A), aspartate aminotransferase (B), oxygen uptake (C) and bile production (D). The in situ bars represent 30 minutes of bile collection in situ (in the 1-hour WI group, this collection predates the WI treatment). Error bars = SD. *P < 0.05 between fresh and WI groups.
Figure 6
Figure 6
Blood results post-transplantation included alanine aminotransferase (A), aspartate aminotransferase (B), total bilirubin (C) and blood urea nitrogen (D). Error bars = SEM. *P < 0.05 between the WI-SNMP group and both the Fresh-SNMP and UW-Control groups.
Figure 7
Figure 7
Histological appearance of liver grafts pre- and posttransplantation (H & E staining and terminal deoxynucleotidyltransferase 2′-deoxyuridine 5′-triphosphate nick-end labeling (TUNEL) staining, respectively). Top: sections from fresh liver, University of Wisconsin (UW) solution group and WI-SNMP groups. Bottom: 30 days posttransplantation autopsic resections from all survivors (UW-Control group, Fresh-SNMP and WI-SNMP groups).
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References

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