title: Improved preservation of warm ischemic livers by hypothermic machine perfusion with supplemented University of Wisconsin solution.
abstract: Hypothermic machine perfusion (HMP) has the potential to improve recovery and preservation of Donation after Cardiac Death (DCD) livers, including uncontrolled DCD livers. However, current perfusion solutions lack the needed substrates to improve energy recovery and minimize hepatic injury, if warm ischemic time (WIT) is extended. This proof-of-concept study tested the hypothesis that the University of Wisconsin (UW) solution supplemented with anaplerotic substrates, calcium chloride, thromboxane A2 inhibitor, and antioxidants could improve HMP preservation and minimize reperfusion injury of warm ischemic livers. Preflushed rat livers subjected to 60 min WIT were preserved for 5 h with standard UW or supplemented UW (SUW) solution. Post preservation hepatic functions and viability were assessed during isolated perfusion with Krebs-Henseleit solution. Livers preserved with SUW showed significantly (p < .001) improved recovery of tissue ATP levels (micromol/g liver), 2.06 +/- 0.10 (mean +/- SE), as compared to the UW group, 0.70 +/- 0.10, and the level was 80% of that of fresh control livers (2.60 +/- 0.13). At the end of 1 h of rewarming, lactate dehydrogenase (U/L) in the perfusate was significantly (p < .05) lower in the SUW group (429 +/- 58) as compared to ischemia-reperfusion (IR) (781 +/- 12) and the UW group (1151 +/- 83). Bile production (microg/min/g liver) was significantly (p < .05) higher in the SUW group (280 +/- 13) as compared to the IR (224 +/- 24) and the UW group (114 +/- 14). The tissue edema formation assessed by tissue wet-dry ratio was significantly (p < .05) higher in UW group. Histology showed well-preserved hepatic structure in the SUW group. In conclusion, this study suggests that HMP with SUW solution has the potential to restore and preserve livers with extended WIT.
authors.affiliation: Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
authors.forename: Shailendra
authors.initials: S
authors.lastname: Jain
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Korneszczuk
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Culberson
authors.forename: James H
authors.initials: JH
authors.lastname: Southard
authors.forename: François
authors.initials: F
authors.lastname: Berthiaume
authors.forename: Jian X
authors.initials: JX
authors.lastname: Zhang
authors.forename: Mark G
authors.initials: MG
authors.lastname: Clemens
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Lee
mesh_terms: D000241:Adenosine; D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000493:Allopurinol; D000818:Animals; D000975:Antioxidants; D001646:Bile / Q000378:metabolism; D002122:Calcium Chloride; D004487:Edema / Q000473:pathology; D005978:Glutathione; D007036:Hypothermia, Induced; D007328:Insulin; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D010477:Perfusion; D011887:Raffinose; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D052096:Warm Ischemia
chemical_list: D000975:Antioxidants; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D013928:Thromboxane A2; D000493:Allopurinol; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D005978:Glutathione; D000241:Adenosine; D002122:Calcium Chloride; D011887:Raffinose