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Positive cardiac inotropic effect of albumin infusion in rats with cirrhosis and ascites: Molecular mechanisms.

Hepatology. 2012 Aug 22;

Authors: Bortoluzzi A, Ceolotto G, Gola E, Sticca A, Bova S, Morando F, Piano S, Silvano F, Rosi S, Gatta A, Angeli P


AIM: The aim is to evaluate effect and molecular mechanism of albumin infusion on cardiac contractility in experimental cirrhosis with ascites. METHODS: Cardiac contractility was recorded ex-vivo in rats with cirrhosis and ascites and in control rats after the injection in the caudal vein of albumin, saline or hydroxyethyl starch. Gene and protein expression of β-receptors and pathways involved in their intracellular signaling such as Gα(i2) protein (Gα(i2) ) and adenylate Cyclase 3 (Adcy3), and protein expression of Tumor Necrosis Factor α (TNF-α) and Inducible Nitric Oxide Synthase (iNOS), were evaluated in cardiac tissue in both groups. Phosphorylation and membrane-traslocation of the cytosolic components of nicotinamide adenine dinucleotide phosphate (NAD(P)H)-oxidase and translocation of nuclear factor-kB(NF-kB) were also evaluated. RESULTS: After saline i.v. injection, cardiac contractility was significantly reduced in rats with cirrhosis as compared to control rats (p<0.01). This was associated with: a) increased expression of protein Gα(i2) (p<0.05), TNF-α (p<0.05), iNOS (p<0.05) b) increased of NAD(P)H-oxidase activity (p<0.05), c) increased nuclear translocation of NF-kB (p<0.05) and d) lower expression of Adcy 3 (p <0.05) in cardiac tissue of rats with cirrhosis. After albumin injection cardiac contractility (p<0.01), protein expression of TNF-α, iNOS, Gα(i2) , and Adcy3, NAD(P)H-oxidase activity and nuclear translocation of NF-kB in cardiac tissue of rats with cirrhosis were reversed to control levels (p<0.05). HES injection did not modify cardiac contractility and nuclear translocation of NF-kB in cardiac tissue of rats with cirrhosis. CONCLUSIONS: Albumin exerts a positive cardiac inotropic effect in rats with cirrhosis and ascites counteracting the negative effects of oxidative stress- and TNF-α-induced activation of NF-kB-iNOS pathway and oxidative stress-induced alteration of β-receptor signaling. (HEPATOLOGY 2012.).

PMID: 22911662 [PubMed - as supplied by publisher]