gms | German Medical Science

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.