Experimental study of a type 3 phosphodiesterase inhibitor on liver graft function.
BACKGROUND
The number of liver transplant recipients is increasing but donor organ shortages have become more severe. The effect of milrinone, a type 3 phosphodiesterase inhibitor (PDEI), on non-heart-beating donor grafts was evaluated using an orthotopic liver transplantation model in rats.


METHODS
Type 3 PDEI or normal saline (control group) was given intravenously to the donor animals for 60 min continuously (50 microg kg-1 min-1 ) before 60 min of warm ischaemia followed by cold preservation and subsequent transplantation. Survival, serum chemistry, bile output, histopathological findings and tissue cyclic 3',5'-adenosine monophosphate (cAMP) concentrations were then compared.


RESULTS
Five of seven animals in the PDEI group were alive at 7 days, compared with only one of seven rats in the control group (P < 0.01). Serum levels of alanine aminotransferase 2 and 6 h after reperfusion, and hyaluronic acid levels 6 h after reperfusion, were significantly lower in the PDEI group than in the control group. Bile output from the transplanted graft was significantly greater in the PDEI group than in controls 2 h after reperfusion (P < 0.01). The mean necrotic area 6 h after reperfusion was also reduced in the PDEI-treated grafts (P < 0.01). cAMP levels in liver tissue at the end of both warm and cold ischaemia, and 2 and 6 h after reperfusion, were significantly higher in the PDEI group compared with those in the control group.


CONCLUSIONS
Type 3 PDEI attenuated the graft injury caused by warm and cold ischaemia and subsequent reperfusion injury via an increase in intracellular cAMP levels. This treatment may be a novel pharmacological intervention for safe and efficient usage of liver grafts from non-heart-beating donors.
Ikegami
T
T
Department of Surgery II, Kyushu University, Fukuoka 812-8582, Japan. tikegami#surg2.med.kyushu-u.ac.jp
Nishizaki
T
T
Hiroshige
S
S
Ohta
R
R
Yanaga
K
K
Sugimachi
K
K
D000818:Animals; D001646:Bile / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D020105:Milrinone / Q000627:therapeutic use*; D023421:Models, Animal; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism; D016019:Survival Analysis
D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D020105:Milrinone