Taurine reduces experimental liver injury after cold ischemic preservation and a period of rewarming prior to reperfusion.
Livers of male Wistar rats (250-300 g) were isolated and flushed with 10 ml of Ringer's solution and 10 ml of UW preservation solution. Then the organs were stored for 24 h at 4 degrees C in UW solution. Livers of Group 1 were rinsed with 10 ml of Ringer's solution and reperfused after hypothermic storage with oxygenated Krebs-Henseleit solution (95% O2; 5% CO2) in a nonrecirculating system at constant pressure (10 mmHg) and 37 degrees C. Livers of Group 2 were incubated for 30 min at 37 degrees C prior to reperfusion, in order to simulate rewarming of the organ upon surgical implantation. Livers of Group 3 were treated like Group 2, but taurine was admixed to the UW solution (1 mM). Livers of Group 1 showed little signs of a preservation/reperfusion injury, with low enzyme activities of the parenchymal ALT and endothelial purine nucleoside phosphorylase (PNP) in the postischemic rinse solution (ALT: 19.9 +/- 12.4; PNP: 3.3 +/- 0.4 U/liter), adequate portal flow values about 3 ml/g/min and high O2 uptake at the end of the experiment (VO2: 3.2 +/- 0.4 ml/100g/min). Livers of Group 2 exhibited nearly tenfold higher enzyme activities in the rinse solution (ALT: 247.0 +/- 94.7*; PNP: 29.5 +/- 17.0* U/l) and disturbed tissue perfusion with significantly reduced flow values of about 2 ml/g/min during the first 10 min of reperfusion. As a result, the recovery of O2 uptake was only 2.2 +/- 0.3 ml/100 g/min*. Addition of taurine (Group 3) resulted in a significant reduction of the enzyme loss (ALT: 96.2 +/- 50.0#; PNP:12.4 +/- 7.0# U/liter) and improved portal flow values and O2 uptake at the end of reperfusion (2.7 +/- 0.3 ml/100 g/min#). The results give evidence for the importance of the rewarming period after hypothermic storage, which is inevitable during implantation of the organ in vivo. Taurine seems to exert a protective effect, affecting both the vascular endothelium and parenchymal tissue (*p < 0.05 vs Group 1; # p < 0.05 vs Group 2).
Institute for Experimental Medicine, University of Cologne, Germany.
T
T
Minor
T
T
Yamaguchi
H
H
Klauke
P
P
Wingenfeld
D
D
Michalk
W
W
Isselhard
D000241:Adenosine; D000410:Alanine Transaminase / Q000032:analysis; D000493:Allopurinol; D000818:Animals; D015415:Biomarkers; D003080:Cold Temperature; D005969:Glutamate Dehydrogenase / Q000032:analysis; D005978:Glutathione; D066298:In Vitro Techniques; D007328:Insulin; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011683:Purine-Nucleoside Phosphorylase / Q000032:analysis; D011887:Raffinose; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D013654:Taurine / Q000494:pharmacology*
D015415:Biomarkers; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D013654:Taurine; D000493:Allopurinol; D005969:Glutamate Dehydrogenase; D011683:Purine-Nucleoside Phosphorylase; D000410:Alanine Transaminase; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose