Effects of splanchnic vasoconstrictors on liver regeneration and survival after 90% rat hepatectomy

Abstract

Purpose: Posthepatectomy liver failure is a serious complication and considered to be caused by increased portal pressure and flow. Splanchnic vasoactive agents and propranolol are known to decrease portal pressure. The aim of this study was to identify optimal candidates with potential for clinical use among somatostatin, terlipressin, and propranolol using rats with 90% hepatectomy. Methods: Rats were divided into 5 groups: sham operation (n = 6), control (n = 20), propranolol (n = 20), somatostatin (n = 20), and terlipressin group (n = 20). Seven-day survival rates and portal pressure change were measured, and biochemical, histologic, and molecular analyses were performed. Results: Portal pressure was significantly decreased in all 3 treatment groups compared to control. All treatment groups showed a tendency of decreased liver injury markers, and somatostatin showed the most prominent effect at 24 hours postoperatively. Histologic liver injury at 24 hours was significantly decreased in propranolol and terlipressin groups (P = 0.016, respectively) and somatostatin group showed borderline significance (P = 0.056). Hepatocyte proliferation was significantly increased after 24 hours in all treatment groups. Median survival was significantly increased in terlipressin group compared to control group (P < 0.01). Conclusion: Terlipressin is considered as the best candidate, while somatostatin has good potential for clinical use, considering their effects on portal pressure and subsequent decrease in liver injury and increase in liver regeneration.