Response of spleen stiffness to portal pressure lowering drugs in a rat model of cirrhosis

Introduction:

Spleen stiffness (SS) is an established parameter to assess portal hypertension which is tightly related to the hemodynamics of blood flow and vascular resistance. Little is known about the response of SS to vasoactive substances. We here studied SS in an TAA-induced cirrhosis rat models after exposure to various vasoactive drugs using a miniaturized Fibroscan platform (µFibroscan).

Aim:

To study the response of SS to the pharmacological modulation of vasoactive durgs.

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. Spleen stiffness was measured by µFibroscan (Echosens, Paris). The rats underwent general anesthesia with isoflurane inhalation. After anesthesia, abdominal aorta and portal vein were cannulated with 24-gauge cannula and connected to Power lab device (AD instruments) to continuously measure the mean arterial pressure (MAP), heart rate (HR) and portal vein pressure (PVP). Drugs were injected systemically and data were collected at time points 0, 15 and 30 mins.

Results:

Cirrhotic rats showed higher LS and SS than the control group (23.8 vs. 3.8 kPa and 19.6 vs. 47.8 kPa, P < 0.0001) and had bigger and heavier spleens (6 vs. 4 cm and 2.7 vs. 1 gm, P < 0.0001, respectively). SS was significantly correlated with spleen size, weight and PVP (r = 0.723, 0.663 and 0.691, respectively< 0.01). Under metoprolol SS, PVP and MAP significantly decreaed (SS = –16.9 kPa, PVP = –3.8 mmHg and MAP = –30 mmHg, P < 0.001). Notably, heart rate significantly increased by 36 beat/min most likely due to counteract low pressure. Udenafil and enalapril showed similar findings with the latter having no effects on heart rate. In contrast, terlipressin did not have any effect on SS while leading to a significant elevation of the PVP and MAP by 2.3 and 58.7 mmHg respectively. Additionally, it had a significant depressive effect on heart rate by 57 beat/min in average. Finally, carvedilol showed significant decline in SS, PVP and MAP (Delta SS = –13.1 kPa, PVP = –5.17 mmHg, MAP = –32 mmHg, P < 0.05).

Conclusion:

SS strongly correlates with spleen size and PVP and responded differently to varous vasoactive drugs. Non-invasive SS measurement could be useful to monitor the patient's response and compliance to portal pressure lowering drugs.