Plasma substance P levels in patients with liver cirrhosis: relationship to systemic and portal hemodynamics.

Abstract

Nitric oxide has been proposed as being responsible for the hyperdynamic circulation observed in portal hypertensive states. Substance P, a neuropeptide partly cleared by liver, induces vasodilation through the activation of the endothelial nitric oxide pathway. This study investigated the plasma levels of substance P in cirrhotic patients and the relationship of these levels to systemic and portal hemodynamics. Sixty-four patients with cirrhosis and 53 healthy controls had blood samples taken for determining plasma values of substance P by ELISA. Systemic and portal hemodynamics were measured on the same day of blood sampling using a Swan-Ganz catheterization and thermodilution technique. Plasma levels of substance P were higher in cirrhotic patients than in healthy controls (45.7 +/- 2.0 vs 32.9 +/- 1.0 pg/ml, p < 0.001) and directly correlated with Child-Pugh's score (r = 0.52, p < 0.0001). Compared with compensated cirrhotic patients, decompensated cirrhotic patients had higher plasma levels of substance P accompanied by a lower systemic vascular resistance and higher hepatic venous pressure gradient. There was no significant correlation between plasma levels of substance P and systemic vascular resistance and hepatic venous pressure gradient. In addition, no significant difference in plasma levels of substance P was observed between cirrhotic patients with and cirrhotic patients without a hepatic venous pressure gradient > 12 mm Hg or between patients with and patients without large esophageal varices. Plasma levels of substance P are increased in patients with cirrhosis and may contribute to the pathogenesis and/or maintenance of hyperdynamic circulation in decompensated patients. The severity of cirrhosis is more important than portal hypertension and the severity of esophageal varices for the development of increased plasma substance P levels.