Hyperdynamic circulation in patients with cirrhosis: direct measurement of nitric oxide levels in hepatic and portal veins

doi:10.1016/S0168-8278(97)80012-8

Journal of Hepatology

Volume 26, Issue 1, January 1997, Pages 75-80

https://doi.org/10.1016/S0168-8278(97)80012-8 Get rights and content

Abstract

Background/Aims: Peripheral vasodilation represents the main vascular dysfunction associated with the hyperdynamic circulation of liver cirrhosis. This study was intended to measure directly regional and systemic levels of nitric oxide, a potent vasorelaxing mediator, in order to assess its role in the development of hemodynamic changes of cirrhosis.

Methods: We compared nitric oxide levels in the splanchnic and systemic circulation of 25 patients with cirrhosis undergoing transjugular intrahepatic portosystemic stent shunt and in the hepatic vein and peripheral blood of 10 patients without cirrhosis submitted to venous catheterization. Nitric oxide levels were measured through electron paramagnetic resonance spectroscopy as nitrosylhemoglobin complexes.

Results: Significantly higher nitric oxide levels were calculated in patients with cirrhosis with respect to controls, both in the peripheral and hepatic veins. In patients with cirrhosis, nitric oxide levels in the portal vein (3.44±2.17, expressed in arbitrary units) were higher than in the systemic circulation (1.89±1.15), but lower than in the hepatic vein (4.75±2.53; p<0.001 by variance analysis).

Conclusions: These data suggest that nitric oxide synthetic pathway activity as well as nitric oxide release are enhanced at the level of splanchnic vasculature and, more important, in the hepatic tissue, confirming evidence of the predominant role of nitric oxide in the pathogenesis of hemodynamic changes in patients with cirrhosis with portal hypertension.

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Right ventricular afterload can increase through multifactorial mechanisms in this population. Firstly, patients with endstage liver disease frequently exhibit a hyperdynamic circulation due to splanchnic vasodilation and the release of humoral factors, which can cause a mild increase in pulmonary pressures [1,2]. Next, the pulmonary vascular resistance can increase through smooth muscle hypertrophy, remodelling and in situ thrombosis resulting in portopulmonary hypertension [3].
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BT causes local/systemic immune defense mechanisms failure and plays a significant role in progression to cirrhosis with the bacterial products leading to activation of monocytes, lymphocytes, and increased serum levels of TNF-α, an inflammatory cytokine with consequent activation of nitric oxide (NO). Activation of NO and increased serum levels contribute to systemic vasodilation, increased cardiac output, decreased mean arterial pressure, and is responsible for variceal growth, ascites, and hepatorenal syndrome.93,94 Bacterial infections are commonly seen in decompensated cirrhotic patients, and SBP is the most common type of infection.
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Acute or chronic insults to the liver are usually followed by a tissue repairing process. Unfortunately, this action, in most cases, is not effective enough to restore the normal hepatic structure and function. Instead, fibrogenesis and regenerative nodules formation ensue, which are relatively nonfunctioning. The common final stage of the process is liver cirrhosis with increased intrahepatic resistance to portal venous blood flow. Throughout the entire course, the extrahepatic circulatory dysfunction, including increased splanchnic blood flow, elevated portal venous blood flow and pressure, decreased splanchnic and peripheral vascular resistance, tachycardia, and increased cardiac output, are noted and denoted as portal hypertension with hyperdynamic circulatory dysfunction. When such a condition is established, patients may suffer from fatal complications such as gastroesophageal variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome. The cause of such a circulatory dysfunction is not fully elucidated. Nevertheless, clarification of the pathophysiology definitely contributes to the control of portal hypertension-related complications. Herein, the molecular mechanism of this intriguing disaster is reviewed and discussed.
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Thirty-six cirrhotic ascitic patients with SBP were examined and classified according to treatment modality (5–7 days) into: Group A received cefotaxime, group B received cefotaxime and albumin 1.5 g/kg body weight within 6 h of SBP being diagnosed and 1 g/kg body weight on day 3, group C received cefotaxime and paracentesis with volume dependent albumin infusion. Control group of 12 cirrhotic ascitic patients free from SBP were included. Routine laboratory tests, ascitic fluid analysis for leucocytes and culture were done, inflammatory mediators such as nitric oxide and tumour necrosis factor alpha were measured in serum and ascitic fluid. Duplex-Doppler assessment of portal flow volume and renal resistive index, Echocardiography to measure end diastolic and end systolic volumes, stroke volume and cardiac output were done. Tests were carried out before and after therapy.
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Ascites denotes the accumulation of fluid in the peritoneal cavity. Different types of ascites can be distinguished depending on its aetiology: portal (e.g. in liver cirrhosis), cardial (e.g. in right heart failure), malignant (e.g. in peritoneal carcinosis), inflammatory or infectious (e.g. in tuberculosis), and chylous ascites (due to injury to the lymphatic vessels). Liver cirrhosis is the most common cause of ascites. During anamnesis the patient should be asked if there has been an increase of the abdominal girth. Abdominal ultrasound is the medical imaging of choice in order to discover even the smallest amount of ascites. Paracentesis is the gold standard for further analysis of ascites through biochemical, cytological and bacteriological procedures. Complications of ascites include primarily spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, and hepatic hydrothorax. Treatment and prognosis of ascites depend on the underlying disease.

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Hyperdynamic circulation in patients with cirrhosis: direct measurement of nitric oxide levels in hepatic and portal veins

Abstract

Gastroenterology

Lancet

Life Sci

Gastroenterology

Gastroenterology

Lancet

J Hepatol

Haemodynamic changes in portal hypertension: new insights in the pathogenesis and clinical implications

Acta Gastroenterol Belg

Hyperdynamic circulation of liver disease 40 years later: pathophysiology and clinical consequences

Hepatology

Portal hypertension

Curr Opin Gastroenterol

Nitric oxide: physiology, pathophysiology and pharmacology

Pharmacol Rev

The L-arginine: nitric oxide pathway

Acta Physiol Scand

Nitric oxide. Biochemistry, pathophysiology, and detection

Am J Clin Pathol

Evidence for normal nitric oxide-mediated vasodilator tone in conscius rats with cirrhosis

Hepatology