Portal-systemic collaterals and angiogenesis.

223 Chronic liver diseases or liver injuries commonly result in increased intrahepatic resistance and subsequently lead to portal hypertension. Portal hypertension is associated with 2 distinct pathophysiologic features: hyper-dynamic circulation and formation of portal-systemic collaterals. 1 Hyperdynamic circulation is characterized by increased splanchnic blood flow, cardiac output, decreased systemic arterial blood pressure and low peripheral vascular resistance. The formation of portal-systemic collaterals is manifested by the appearance of esophageal or gastric varices. These collateral vessels will shunt part of the portal blood flow bypassing the liver to systemic circulation. Shunting the portal blood flow through collateral vessels is an attempt to decompress the highly pressurized portal system. However, the formation of collateral vessels may lead to serious clinical events such as variceal rupture and bleeding, which carries a high risk of morbidity and mortality. Therefore, revealing the mechanism underlying the development of portal-systemic collaterals is an important issue and has been extensively investigated in recent years. Both non-cirrhotic and cirrhotic models of portal hypertension have been extensively used in studies of the pathophysiology of portal hypertension and portal-systemic collaterals. The partial portal vein ligation (PVL) model has been widely used in the study of portal hypertension due to its reproducibility and being easy to perform. In the PVL model, portal-systemic collaterals can be detected as early as 2 days and develop fully after 1 week. The degree of shunting is very high and may approach 100%. The main drawback of the PVL model is that, contrary to the usual clinical situation , portal hypertension will gradually decrease after the establishment of portal-systemic collaterals. Thus, cirrhotic models of portal hypertension are closer to the real pathophysiology of cirrhotic patients in clinical practice. Cirrhotic models of portal hypertension are commonly induced by common bile duct ligation (CBDL), or liver toxins such as carbon tetrachloride and thioacetamide. In these models, the degrees of portal-systemic shunting developed gradually by time of liver injury and varied widely from less than 30% up to 60%, and were generally lower than in the PVL model. Progress in understanding the pathophysiology and pharmacology of portal-systemic collaterals relies greatly on the technique of in situ perfusion of collateral circulation developed by Mosca et al in 1992. 2 They showed in PVL rats that several vasoactive substances produce direct vasodilatory or vasoconstrictory effects on collaterals. In addition, different types of receptors including α-receptor, β-receptor and 5-hydroxytrypt-amine receptors were expressed on …