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

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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

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Phosphodiesterase 3 Inhibitors
Phosphodiesterase Inhibitors
Reperfusion
Warm Ischemia
Transplants
Adenosine Monophosphate
Control Groups
Liver
Cold Ischemia
Tissue Donors
Bile
Milrinone
Hyaluronic Acid
Reperfusion Injury
Serum
Alanine Transaminase
Liver Transplantation
Transplantation
Pharmacology
Survival

All Science Journal Classification (ASJC) codes

  • Surgery

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Experimental study of a type 3 phosphodiesterase inhibitor on liver graft function. / Ikegami, Toru; Nishizaki, T.; Hiroshige, S.; Ohta, R.; Yanaga, K.; Sugimachi, K.

In: British Journal of Surgery, Vol. 88, No. 1, 03.02.2001, p. 59-64.

Research output: Contribution to journalArticle

Ikegami, Toru ; Nishizaki, T. ; Hiroshige, S. ; Ohta, R. ; Yanaga, K. ; Sugimachi, K. / Experimental study of a type 3 phosphodiesterase inhibitor on liver graft function. In: British Journal of Surgery. 2001 ; Vol. 88, No. 1. pp. 59-64.
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