This is the Scientific Surgery Archive, which contains all randomized clinical trials in surgery that have been identified by searching the top 50 English language medical journal issues since January 1998. Compiled by Jonothan J. Earnshaw, former Editor-in-Chief, BJS
Experimental study of a type 3 phosphodiesterase inhibitor on liver graft function. BJS 2001; 88: 59-64.
Published: 6th December 2002
Authors: T. Ikegami, T. Nishizaki, S. Hiroshige, R. Ohta, K. Yanaga, K. Sugimachi et al.
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.
Method
Type 3 PDEI or normal saline (control group) was given intravenously to the donor animals for 60 min continuously (50 µg 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.
Conclusion
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. © 2001 British Journal of Surgery Society Ltd
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