Cardiac modifications occurring in the ascitic rat with biliary cirrhosis are nitric oxide related

doi:10.1016/S0168-8278(96)80272-8

Journal of Hepatology

Volume 24, Issue 6, June 1996, Pages 747-752

https://doi.org/10.1016/S0168-8278(96)80272-8 Get rights and content

Abstract

Background/Aims: Although the cardiac output is increased in liver cirrhosis, some degree of cardiac failure could coexist as suggested by human investigations showing cardiac enlargement in cirrhosis and by animal studies describing a limited response to fluid loading in the cirrhotic rat. Endotoxemia induces similar hemodynamic changes during the septic shock. This septic cardiomyopathy has been attributed to an increased secretion of nitric oxide by the myocytes. In this study, we aimed to verify if cirrhotic cardiomyopathy was present in the rat with biliary cirrhosis, and if it could be related to abnormal nitric oxide secretion.

Methods: We therefore compared the coronary pressure, the systolic ventricular pressure and the peak rate of rise of the left ventricular pressure obtained from isolated hearts perfused with a modified Langedorff apparatus in control rats and in cirrhotic rats obtained by bile duct ligation. The variations occurring after inhibition of nitric oxide synthesis by the addition of N^g monomethyl-L-arginine (10⁻⁶M) to the perfusing Krebs-Ringer solution wee also studied in both groups.

Results: We found that the coronary pressure and the contractility of the cirrhotic hearts decreased significantly when compared to the controls. Inhibition of the nitric oxide synthesis increased those values significantly when the hearts were obtained from cirrhotic animals. This was not observed in the control group.

Conclusion: Our data suggest that the cardiac modifications induced by the cirrhosis in the studied parameters are related to nitric oxide.

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Conversely, bupropion (30 and 60 mg/kg) reduced prolonged QTc, QRS and RR intervals. Moreover, in our experiment, the contractility of isolated papillary muscle reacting to isoproterenol stimulation was considerably impaired, which was in line with preceding results from bile duct-ligated (BDL) rats (van Obbergh, Vallieres et al. 1996, Liu, Ma et al. 2000). In cirrhotic rats, isoproterenol Rmax (10-5 M) on chronotropic and inotropic responses were markedly dropped in the atria and papillary muscles, and the expression and sensitivity of β-adrenergic receptors and their post-receptor signaling path in the heart are blunted (Lee, Marty et al. 1990, Ebrahimi, Tavakoli et al. 2006).
Bupropion, an atypical anti-depressant and smoking cessation aid, attenuates complications arising from the activation of inflammatory and oxidative pathways. In this study, the effect of bupropion on an inflammatory and oxidative condition induced by carbon tetrachloride (CCl₄) namely cirrhotic cardiomyopathy (CCM) was investigated in rats. CCM was induced by intraperitoneal injection of CCl₄ (0.4 g/kg, i.p.). Bupropion was treated orally at doses 30 and 60 (mg/kg, p.o.) for 8 weeks. CCl₄ treatment significantly lowered hepatic antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) while enhanced Malondialdehyde (MDA). Elevations in serum nitric oxide (NO) metabolites nitrite/nitrate, and cardiac tumor necrosis factor alpha (TNF-α) and interleukin 1-beta (IL-1β) levels were observed. Cirrhosis also decreased contractility in response to isoproterenol (10⁻¹⁰ to 10⁻⁵ M). The spleen weight and intrasplenic pressure increased and QTc, QRS and RR intervals prolonged. Pathological damages in the liver for example focal necrosis, fibrosis and the hepatic blocking increased. On the other hand, bupropion increased GSH, CAT and SOD and lowered MDA. Bupropion reduced NO metabolites and TNF-α levels and decreased IL-1β. The cardiac contractile force improved at maximal effect (Rmax) 10^-5 M by bupropion. The intrasplenic pressure was reduced by bupropion. Bupropion reduces QTc, QRS and RR intervals and the liver tissue damages. Bupropion played a cardioprotective role reducing inflammatory and oxidative factors. It may recover the impairment of cardiac contractility and hyperdynamic condition in CCM, and this effect could be mediated at least in part by a NO-dependent mechanism.
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Cardiac modifications occurring in the ascitic rat with biliary cirrhosis are nitric oxide related

Abstract

Am J Cardiol

Lancet

Eur J Pharm

J Mol Cell Cardiol

Chest

Lancet

Impaired left ventricular function in alcoholic cirrhosis with ascites

Circulation

Cardiac abnormalities in liver cirrhosis

West J Med

Limited cardiac preload reserve in conscious cirrhotic rats

Am J Physiol

The “jaundiced heart”: a possible explanation for postoperative shock in obstructive jaundice

Surgery

Pathogenesis of arterial hypotension in cirrhotic rats with ascites: role of endogenous nitric oxide

Hepatology

The endothelial and nonendothelial mechanism responsible for attenuated vasoconstriction in cirrhotic rats

Exp Physiol

The nitric oxide hypothesis and the hyperdynamic circulatin in cirrhosis

Hepatology

Nitric oxide and endotoxemia

Circulation

Nitric oxide: physiology, pathophysiology and pharmacology

Pharmacol Rev