Lipoic Acid Prevents Development of the Hyperdynamic Circulation in Anesthetized Rats With Biliary Cirrhosis

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Abstract
Chronic bile duct ligation is associated with the development of oxidant injury, biliary cirrhosis, portal hypertension, and a hyperdynamic circulation. We have previously demonstrated that the hyperdynamic circulation in the partial portal vein-ligated rat can be prevented by the administration of N–acetylcysteine. To extend these findings, we have examined the effect of lipoic acid, a thiol–containing antioxidant, on hemodynamics, oxidative stress, and nitric oxide (NO) production in bile duct-ligated (BDL) cirrhotic rats. Lipoic acid was given continuously in drinking water to normal and BDL rats; control rats received ordinary drinking water, and animals were studied at 24 days following surgery. Lipoic acid prevented the development of the hyperdynamic circulation (cardiac index [CI]: 15.7 ± 2.0 vs. 29.5 ± 2.1 mL · min-1 · 100 g-1; P < .05) and significantly attenuated the rise in portal pressure (PP) (12.7 ± 0.8 vs. 15.2 ± 0.5 mm Hg; P < .05). Hepatic nitric oxide synthase (NOS) activity and plasma nitrite/nitrate concentration increased significantly following bile duct ligation, and both of these were prevented by lipoic acid. Lipoic acid had no effect on the biochemical or histological parameters of liver function in the cirrhotic group. We conclude that lipoic acid prevents the development of the hyperdynamic circulation in the rat model of biliary cirrhosis, and that this is associated with decreased synthesis of NO.(Hepatology 1999;29:1358–1363.)