Protective effects of ambroxol in hypothermic liver preservation: a transplant study.
The bronchosecretolytic agent ambroxol added to histidine-tryptophan-ketoglutarate (HTK) solution has recently been shown to protect cold stored rat hepatocytes. The aim of the present study was to confirm these observations in a rat liver transplantation model. Before orthotopic liver transplantation, donor livers from 30 syngeneic Wistar rats were assigned to three groups (n = 10): (A) in situ flush (ISF) and 1/2-h cold storage (CS) with HTK solution, (B) ISF and 3-h CS with HTK, and (C) ISF and 3-h CS with HTK + 10(-3) mol/L ambroxol. The efficacy of the drug was evaluated by postoperative survival (> 14 days) and liver enzyme release (ALT), bile flow, histomorphological injury, and malondialdehyde (MDA) level in the grafts 15 min after reperfusion. After 1/2-h CS with HTK solution (A), 90% of the transplanted rats survived. In comparison with donor conditions, bile flow in the reperfused grafts decreased to 87 +/- 5.3%, whereas postoperative ALT levels slightly increased. After 3-h HTK preservation (B), the survival rate decreased to 60%, while ALT values markedly increased and bile flow after reperfusion declined to 82 +/- 6.6%. Ambroxol added to HTK solution (C) enhanced bile flow to 106 +/- 3.4%(p < .05), and reduced ALT and MDA levels and histomorphological injury of the transplanted livers, so that its beneficial effect in organ preservation has been confirmed in the transplant model. However, survival rate was not improved by the agent, probably because of the low cold ischemia tolerance of the Wistar rat livers used.
Drews
G
G
Department of Surgery, University of Leipzig, Germany.
Tannapfel
A
A
Gnauk
H G
HG
Palmes
D
D
Martin
R
R
Hauss
J
J
Spiegel
H U
HU
D000410:Alanine Transaminase / Q000378:metabolism; D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D001646:Bile / Q000378:metabolism; D002470:Cell Survival; D003080:Cold Temperature; D005100:Expectorants / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology / Q000637:transplantation*; D016031:Liver Transplantation / Q000379:methods* / Q000401:mortality; D008315:Malondialdehyde / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014021:Tissue Preservation / Q000379:methods*
C039984:Bretschneider cardioplegic solution; D005100:Expectorants; D000551:Ambroxol; D008353:Mannitol; D008315:Malondialdehyde; D011343:Procaine; D011189:Potassium Chloride; D000410:Alanine Transaminase; D005947:Glucose