RSS-Feed abonnieren
DOI: 10.1055/s-0038-1677059
Liver stiffness decreases in response to portal pressure lowering drugs
Publikationsverlauf
Publikationsdatum:
04. Januar 2019 (online)
Background:
Liver stiffness (LS) is increasingly used to screen for liver fibrosis. Besides fibrosis, however, LS is also significantly modulated by pressure-related confounders such as arterial, portal and central venous pressure. It is still poorly understood how LS responds to pharmacological modulation of these pressure e.g. using vasoactive substances.
Aim:
Assess pressures and LS in a TAA-induced cirrhosis rat model in response to various vasoactive drugs.
Methods:
We induced cirrhosis in 24 wildtype 8 weeks old adult male Wistar rats with 200 mg/Kg dosage of Thioacetamide (TAA) through intraperitoneal injection of 50 mg/ml solution 2 times per week for 6 weeks. The six groups consisted of control (sodium chloride), metoprolol, udenafil, enalapril, terlipressin and carvidelol. Liver and spleen stiffness were measured by µFibroscan (Echosens, Paris). The rats underwent general anesthesia with isoflurane inhalation. Invasively after anesthesia, abdominal aorta and portal vein were cannulated and connected to Power lab device (AD instruments) to measure the mean arterial pressure (MAP), heart rate (HR) and portal vein pressure (PVP) continuously during the procedure. Drugs were injected systemically and rats were monitored for pressure. Changes and LS values for 30 minutes.
Results:
In all drugs, LS followed tightly the change of the portal vein pressure (r = 0.66, P < 0.01). On the other side, important differences were observed between the drug cohorts. While a significant decrease of PVP and LS (16% to 30%, P < 0.05) was seen after 15 and 30 minutes with metoprolol, udenafil, enalapril and carvedilol, terlipressin only showed a slight decrease within the first 15 minutes (20%, P < 0.05). Moreover, PVP and LS significantly increased after 30 minutes (+10%, P < 0.05). Overall, carvedilol showed the strongest decrease of PVP and LS of about 40%. Of note, the heart rate increased after metoprolol and udenafil injection (ca. 10%), while it showed no change after enalapril application. In contrast, terlipressin and carvedilol decreased the heart rate by ca 30%.
Conclusion:
LS correlates significantly with portal pressure and mirroring non-invasively the portal pressure-lowering effects of drugs such as carvedilol. In the future, LS could be a valuable tool to monitor the efficacy of portal pressure lowering drugs, a still insufficiently solved problem.