Experimental study of a type 3 phosphodiesterase inhibitor on liver graft function

Toru Ikegami, T. Nishizaki, S. Hiroshige, R. Ohta, K. Yanaga, K. Sugimachi

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Abstract

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 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.

Original languageEnglish
Pages (from-to)59-64
Number of pages6
JournalBritish Journal of Surgery
Volume88
Issue number1
DOIs
Publication statusPublished - Feb 3 2001

All Science Journal Classification (ASJC) codes

  • Surgery

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    Ikegami, T., Nishizaki, T., Hiroshige, S., Ohta, R., Yanaga, K., & Sugimachi, K. (2001). Experimental study of a type 3 phosphodiesterase inhibitor on liver graft function. British Journal of Surgery, 88(1), 59-64. https://doi.org/10.1046/j.1365-2168.2001.01621.x