Improved liver preservation for transplantation due to calcium channel blockade.
Intracellular calcium is an important determinant for cell death in organ hypothermic preservation for transplantation. In this study, we show that prevention of calcium entry improves the result of liver cold storage in UW solution. The isolated perfused rabbit liver was used. After 48 hr of cold storage in UW solution, bile production was reduced by 70% (P less than 0.005). However, by adding the calcium channel blockers verapamil or nifedipine (40 microM) to the UW solution, this reduction was abolished, and the livers produced the same amount of bile as unpreserved livers. Furthermore, addition of the calcium channel activator, BAY K8644 (40 microM), to the UW solution, reduced bile production by 50% (P less than 0.01) already after preservation for 24 hr. We conclude that calcium entry is of importance for liver function after preservation and cold storage, and that including a calcium channel blocker to the preservation solution makes long-term liver preservation safer.
Ar'Rajab
A
A
Department of Surgery, Lund University, Sweden.
Ahrén
B
B
Bengmark
S
S
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005978:Glutathione; D007328:Insulin; D008099:Liver / Q000187:drug effects*; D016031:Liver Transplantation; D009543:Nifedipine / Q000494:pharmacology; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011817:Rabbits; D011887:Raffinose; D012996:Solutions; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007328:Insulin; D019188:Organ Preservation Solutions; D012996:Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D005978:Glutathione; D009543:Nifedipine; D000241:Adenosine; D011887:Raffinose