ABSTRACT
Background/Aims@#Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy. @*Methods@#Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy. @*Results@#Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls. @*Conclusion@#Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.
ABSTRACT
Nonselective beta-adrenergic blocker (NSBB) therapy for the prevention of initial and recurrent gastrointestinal bleeding in cirrhotic patients with gastroesophageal varices has been used for the past four decades. NSBB therapy is considered the cornerstone of treatment for varices, and has become the standard of care. However, a 2010 study from the group that pioneered β-blocker therapy suggested a detrimental effect of NSBBs in decompensated cirrhosis, especially in patients with refractory ascites. Since then, numerous additional studies have incompletely resolved whether NSBBs are deleterious, although more recent evidence weighs against a harmful effect. The possibility of a “therapeutic window” has also been raised. We aimed to review the literature to analyze the pros and cons of using NSBBs in patients with cirrhosis, not only with respect to bleeding or mortality but also to other potential benefits and risks. β-blockers are highly effective in preventing first bleeding and recurrent bleeding. Furthermore, NSBBs improve congestion/ischemia of the gut mucosa, decrease intestinal permeability, and therefore indirectly alleviate systemic inflammation. β-blockers shorten the electrocardiographic prolonged QTc interval and may also decrease the incidence of hepatocellular carcinoma. On the other hand, the possibility of deleterious effects in cirrhosis has not been completely eliminated. NSBBs may be associated with an increased risk of portal vein thrombosis, although this could be correlational artifact. Overall, we conclude that β-blockers in cirrhosis are much more of a friend than enemy.
ABSTRACT
Nonselective beta-adrenergic blocker (NSBB) therapy for the prevention of initial and recurrent gastrointestinal bleeding in cirrhotic patients with gastroesophageal varices has been used for the past four decades. NSBB therapy is considered the cornerstone of treatment for varices, and has become the standard of care. However, a 2010 study from the group that pioneered β-blocker therapy suggested a detrimental effect of NSBBs in decompensated cirrhosis, especially in patients with refractory ascites. Since then, numerous additional studies have incompletely resolved whether NSBBs are deleterious, although more recent evidence weighs against a harmful effect. The possibility of a “therapeutic window” has also been raised. We aimed to review the literature to analyze the pros and cons of using NSBBs in patients with cirrhosis, not only with respect to bleeding or mortality but also to other potential benefits and risks. β-blockers are highly effective in preventing first bleeding and recurrent bleeding. Furthermore, NSBBs improve congestion/ischemia of the gut mucosa, decrease intestinal permeability, and therefore indirectly alleviate systemic inflammation. β-blockers shorten the electrocardiographic prolonged QTc interval and may also decrease the incidence of hepatocellular carcinoma. On the other hand, the possibility of deleterious effects in cirrhosis has not been completely eliminated. NSBBs may be associated with an increased risk of portal vein thrombosis, although this could be correlational artifact. Overall, we conclude that β-blockers in cirrhosis are much more of a friend than enemy.