NCX-1000, a nitric oxide-releasing derivative of ursodeoxycholic acid, ameliorates portal hypertension and lowers norepinephrine-induced intrahepatic resistance in the isolated and perfused rat liver

Abbate

Journal of the American College of Cardiology

et al. 2010

314

276

Cirrhotic cardiomyopathy is a clinical syndrome in patients with liver cirrhosis characterized by an abnormal and blunted response to physiologic, pathologic, or pharmacologic stress but normal to increased cardiac output and contractility at rest. As many as 50% of cirrhotic patients undergoing liver transplantation show signs of cardiac dysfunction, and 7% to 21% of deaths after orthotopic liver transplantation result from overt heart failure. In this review, we critically evaluate the existing literature on the pathophysiology and clinical implications of cirrhotic cardiomyopathy.

Section: Potential Therapeutic Approachesmentioning

confidence: 99%

Cirrhotic Cardiomyopathy

Abbate

Journal of the American College of Cardiology

et al. 2010

314

276

“…In addition, cirrhotic patients with concomitant severe cardiomyopathy may benefit from cardiac transplantation [96]. receptor agonists are responsible for hydrogen sulfide production; moreover, NCX-1000 may release NO in the liver [97]. These agents are promising for future therapeutic regimens but their exact role is not yet elucidated in CCM.…”

Section: Liver Transplantationmentioning

confidence: 99%

Pathophysiological and Clinical Approach to Cirrhotic Cardiomyopathy

Páll¹,

Czifra²,

Vitális³

et al. 2014

JGLD

Hyperdynamic circulation, systolic and diastolic left ventricular dysfunction and certain electrophysiological abnormalities have been associated with cirrhosis and known for a long time. These clinical features have been introduced as cirrhotic cardiomyopathy (CCM), which is characterized by blunted myocardial contractile responsiveness to physical, physiological and pharmacological stress. Importantly, cardiac dysfunction can be reversible and can improve due to effective medical treatment and also after liver transplantation. Echocardiography and electrocardiography are essential tools for recognizing the characteristic changes in the myocardial function and also the alterations in the electrophysiological properties of the heart. Laboratory markers are auxiliary modalities further aiding the establishment of the correct diagnosis. In this review, we aimed to collect the pathophysiological background and clinical characteristics of CCM with the intention of summarizing the current possibilities for the diagnosis establishment and treatment of this cardio-hepatic disorder.Abbreviations: A: late diastolic transmitral peak flow velocity; ACE: angiotensin converting enzyme; ANP: atrial natriuretic peptide; ARB: angiotensin receptor blocker; BNP: brain natriuretic peptide; cAMP: cyclic adenosine monophosphate; CCM: cirrhotic cardiomyopathy; CGRP: calcitonin gene-related peptide; CO: carbon monoxide; DD: diastolic dysfunction; DT: deceleration time; E: early diastolic transmitral peak flow velocity; Ea: early diastolic velocity of the septal mitral annulus; EF: ejection fraction; MUGA: Multi Gated Acquisition Scan; NO: nitric oxide; NSBB: non-selective beta-blocker; pro-BNP: pro-brain natriuretic peptide; QTc: corrected QT interval; RAAS: renin-angiotensin aldosterone system; RALES: Randomized Aldactone Evaluation Study; suPAR: urokinase-type plasminogen activator receptor; TDI: Tissue Doppler Imaging; TIPS: transjugular intrahepatic portosystemic shunt; TNF-alpha: tumor necrosis factor-alpha.

“…The drug that has shown more promising results in experimental studies is NCX-1000, an NO-releasing derivative of ursodeoxycholic acid [118] . NCX-1000 has been shown to reduce hepatic resistance in two different models of cirrhosis [118][119][120] , without affecting systemic hemodynamics. There are no data on the effects of this drug in patients with cirrhosis.…”

Section: Selective Hepatic Delivery Of Nomentioning

confidence: 99%

Variceal Bleeding: Pharmacological Therapy

Bosch

Abraldes

2005

Dig Dis

The complications of portal hypertension are totally prevented if hepatic venous pressure gradient is decreased below 12 mm Hg. Besides, if this target is not achieved, a 20% decrease in portal pressure from baseline levels offers an almost total protection from variceal bleeding. This sets the rationale for drug therapy to reduce portal pressure in portal hypertension. Pharmacological therapy to decrease portal pressure includes vasoconstrictors to decrease portal blood inflow, vasodilators to decrease hepatic resistance, and combination therapy. Oral agents, such as b-adrenergic blockers and organic nitrates, are used for long-term prevention of variceal bleeding, while parenteral agents, such as somatostatin (and analogues) and terlipressin, are used for the treatment of acute variceal bleeding.