gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Effekt of Cilostazol® on hepatic microcirculation and liver regeneration after partial hepatectomy in a rat model

Meeting Abstract

  • Stefan Dold - Universitätsklinik Homburg/Saar, Klinik f. Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie, Homburg
  • Maximilian von Heesen - Universitätsklinik Homburg/Saar, Klinik f. Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie, Homburg
  • Simon Müller - Universitätsklinik Homburg/Saar, Institut f. Experimentelle Chirurgie, Homburg
  • Otto Kollmar - Klinik für Plastische-, Hand und Wiederherstellungschirurgie, Klinik für Allgemeine Chirurgie, Viszeral-, Gefäß- und Kinderchirurgie, Homburg
  • Martin Schilling - Universitätsklinik Homburg/Saar, Klinik f. Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie, Homburg a.d. Saar
  • Michael Dieter Menger - Universitätsklinik Homburg/Saar, Institut f. Experimentelle Chirurgie, Homburg a.d. Saar
  • Mohamed Moussavian - Universitätsklinik Homburg/Saar, Klinik f. Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie, Homburg

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch816

DOI: 10.3205/11dgch816, URN: urn:nbn:de:0183-11dgch8163

Published: May 20, 2011

© 2011 Dold et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Introduction: Major liver resection for primary or colorectal liver tumors was associated with postoperative liver dysfunction and liver failure. So far no efficient treatment was established to improve patient outcome after extended liver resections. The aim of our study was to elucidate if pretreatment with Cilostazol®, a selective phosphodiesterase (PDE)-III-Inhibitor was capable to impair hepatic perfusion and liver regeneration after major hepatectomy.

Materials and methods: Sprague-Dawley rats (n=64) were pretreated with Cilostazol® (5mg/kg KG) or glucose solution. After 5 days animals underwent 70% liver resection. After surgical treatment as well as on 1., 3. and 6. postoperative day (each n=8) hepatic arterial and portal venous blood flow were analyzed by ultrasonic flow measurement. Microvascular blood flow was determined by laser-Doppler-flowmetrie (LDF). Hepatic function and liver regeneration were characterized by bile excretion and liver histology (PCNA and cleaved caspase-3). Cilostazol® or placebo was given until end of experiment. Additional animals (n=16) received PDEIII-inhibitor or placebo and no liver resection. Mean values ± SEM, p <0,05.

Results: Pretreatment with the PDE-III-Inhibitor resulted in a significantly impaired portal venous blood flow (2,00 ±0,07 vs. 1,56±0,11 ml/g*min; p<0,05) and improved hepatic microcirculation (642,9±41,1 vs. 493,8±25,0 aU; p<0,05) when no liver resection was performed. Portal blood flow and hepatic microcirculation were increased 77 % and 32% respectively after 70% hepatectomy, where as hepatoarterial blood flow was found unchanged. Cilostazol treate-ment was also associated with an additional improvement of hepatic blood flow and microcir-culation. Interestingly liver regeneration was found enhanced by cilostazol administration over the whole observation period, with a maximum on the first day after liver resection (32±4 vs. 20±2 PCNA +cells/HPF p<0,05). No relevant apoptosis was detected in any group.

Conclusion: We could demonstrate that preconditional PDE-III inhibition can improve hepatic perfusion and liver regeneration after 70% hepatectomy. Thus, PDE-III inhibitors may represent an efficient drug therapy to ameliorate liver regeneration and hepatic function after extended liver resection.