Hemodynamic Assessment of the Development of Portal-Systemic Collaterals in Portal Hypertensive Rats

Abstract

Portal hypertension induced the formation of portal-systemic collaterals. Revealing the developmental change of portal-systemic collaterals is important for future therapy. We observed the evolution of an accessible shunting vessel, the spleno-renal shunt (SRS), in rats after induction of portal hypertension by partial portal vein ligation (PVL). The hemodynamic and histological assessments of SRS were performed by transit time ultrasound and immunohistochemical studies. The portal pressure of PVL rats surged to 16.5 ± 1.1 mmHg on day 1 after ligation surgery and was maintained at a significantly higher level (13.0 ± 0.4 mmHg) to day 14 when compared to sham rats (p < 0.05). The size or flow of SRS in PVL rats did not change immediately after portal pressure surge. Instead, they increased rapidly on day 4, peaked on day 7, and stabilized thereafter. The size and flow were greater and the resistance of SRS was lower in PVL rats after day 7 (p < 0.05). The anti-Ki67 immunohistochemical study demonstrated positive staining of endothelium in SRS and negative in portal vein or aorta of PVL rats. In addition, the endothelial cells of SRS were stained positive for CD31 and KLF5. We concluded that the pressure-induced opening of pre-existing vessels was not the primary underlying mechanism in the formation of SRS. Endothelial proliferating and vascular remodeling process participated actively during the development of SRS. These observations can be used for studying the pathogenesis and developing more effective anti-portal hypertensive therapy in the future.