research article

Pharmacological Modulation of Liver and Spleen Stiffness in a Cirrhotic Rat Model

Abstract

Omar Elshaarawy,1– 3 Shami Hasan M Alquzi,1 Felix Piecha,1,4 Vanessa Rausch,1 Johannes Mueller,1 Sebastian Mueller1 1Center for Alcohol Research, University of Heidelberg, Heidelberg, BW, Germany; 2Department of Gastroenterology, Liver Unit, Liverpool University Hospitals Foundation Trust, University of Liverpool, Liverpool, UK; 3Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shibin el Kom, Menoufia Governorate, Egypt; 4Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyCorrespondence: Sebastian Mueller, Center for Alcohol Research, University of Heidelberg, INF 350, Heidelberg, BW, 69120, Germany, Tel +49 6221 567121, Email [email protected]: Liver stiffness (LS) assesses liver fibrosis, while spleen stiffness (SS) is a promising marker for portal hypertension (PH), reflecting blood flow and vascular resistance. However, the response of LS and SS to vasoactive drugs is unclear. This study evaluates the effects of various PH-lowering drugs on LS and SS in a rat cirrhosis model.Patients and Methods: In this study, cirrhosis was induced in 43 male Wistar rats (8 weeks old) via intraperitoneal thioacetamide (TAA) injections (200 mg/kg, twice weekly for six weeks). Rats were divided into six groups: control (sodium chloride), metoprolol, udenafil, enalapril, terlipressin, and carvedilol. LS and SS were measured using μFibroscan. Mean arterial pressure (MAP), heart rate (HR), and portal vein pressure (PVP) were continuously monitored. Drugs were administered systemically, with data collected at 0, 15, and 30 minutes.Results: TAA-treated rats exhibited significantly higher LS and SS compared to controls (22.1 vs 4.2 kPa and 53.7 vs 27.7 kPa; P < 0.001). Changes in LS and SS correlated with PVP (r = 0.670 for LS and r = 0.867 for SS; P < 0.01). Metoprolol, udenafil, enalapril, and carvedilol significantly reduced PVP (22– 34%, P < 0.05), accompanied by decreases in LS and SS (13– 37%, P < 0.05). Terlipressin did not reduce LS or SS, likely due to opposing effects of increased MAP and reduced PVP.Conclusion: In conclusion, combined LS and SS measurements may provide valuable non-invasive insights into patient responses and adherence to PH-lowering therapies.Keywords: spleen stiffness, liver stiffness, cirrhosis, portal pressure, terlipressi

    Similar works