Occurrence and progression of hemodynamic dysfunction in cirrhotic portal hypertension / 中华消化外科杂志

Cirrhotic portal hypertension refers to a series of syndroms characterized by structural abnormality and dysfunction of hepatic sinusoid caused by chronic liver injury and obstructing portal-systemic blood flow, resulting in gradually increased portal venous system pressure as clinical manifestations. Increased intrahepatic resistance and portal venous system blood flow are main causes for cirrhotic portal hypertension. The structural abnormality and dysfunction of hepatic sinusoid cause not only increased intrahepatic resistance, but also substance exchange barriers between hepatic sinusoidal blood and hepatocytes, resulting in splanchnic artery dilation and increased blood flow and pressure of portal venous system. Dysfunction of splanchnic hemodynamic is an important factor for hyperdynamic circulation in cirrhotic portal hypertension. As the disease progresses, cirrhotic portal hypertension can continuously promote the activation of hyperdynamic circulation, which in turn can accelerate the development of cirrhotic portal hyperten-sion. This vicious circle is the main reason for the irreversible and untreatable end-stage liver disease. The authors review the pathophysiological mechanisms of cirrhotic portal hypertension, splanchnic hemodynamic dysfunction and hyperdynamic circulation.

Cirrhotic cardiomyopathy: the liver affects the heart

Cirrhotic cardiomyopathy historically has been confused as alcoholic cardiomyopathy. The key points for diagnosis of cirrhotic cardiomyopathy have been well explained, however this entity was neglected for a long time. Nowadays the diagnosis of this entity has become important because it is a factor that contributes significantly to morbidity-mortality in cirrhotic patients. Characteristics of cirrhotic cardiomyopathy are a hyperdynamic circulatory state, altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, particularity QT interval prolongation. The pathogenesis includes impaired function of beta-receptors, altered transmembrane currents and overproduction of cardiodepressant factors, such as nitric oxide, cytokines and endogenous cannabinoids. In addition to physical signs of hyperdynamic state and heart failure under stress conditions, the diagnosis can be done with dosage of serum markers, electrocardiography, echocardiography and magnetic resonance. The treatment is mainly supportive, but orthotopic liver transplantation appears to improve this condition although the prognosis of liver transplantation in patients with cirrhotic cardiomyopathy is uncertain.

Circulación hiperdinámica de pacientes cirróticos: expresión renal de los efectos del propranolol / HYPERDYNAMIC CIRCULATION IN CIRRHOTIC PATIENTS: RENAL EXPRESSION OF EFFECTS OF PROPRANOLOL

Introducción: A fin de investigar los daños potenciales sobre el funcionalismo renal que pueden causar los medicamentos beta bloqueantes no selectivos (BBNS) en cirróticos con descompensación extrema de su equilibrio hemodinámico se evaluaron sus efectos administrándolos a enfermos con cirrosis y ascitis, con diferente grado de descompensación. Métodos: Se estudiaron dos fases: pre y post administración de propranolol, midiendo presión arterial media (PAM), y analítica sanguínea y urinaria, en 20 pacientes: diez con ascitis compensada y diez con ascitis más Peritonitis Bacteriana Espontánea (PBE), y un grupo control de diez individuos sin enfermedad hepática. Resultados: La concentración de sodio urinario/día obtuvo diferencia significativa (p<0.04) entre los pacientes y controles sin tratamiento, así como la Tasa de Reabsorción de sodio (p<0.04) entre pacientes compensados y pacientes con PBE previo al tratamiento. También se obtuvo diferencia significativa en los pacientes sin PBE antes y después del tratamiento, pero no se manifestó en el grupo con PBE al evaluar las dos fases, aunque la excreción del sodio si mostró tendencia a la disminución. La disminución de la Presión Arterial Media (PAM) considerada factor pronóstico de severidad obtuvo correlación positiva con la excreción de sodio en el grupo de pacientes Child C con PBE post trata- miento. Conclusiones: Los pacientes con extenso grado de descompensación hepática y hemodinámica son susceptibles de deterioro renal y hemodinámico con el tratamiento de pro- pranolol.

Introduction: To investigate the potential damage to the kidney function that can cause non-selective beta blocker drugs (BBNS) in cirrhotic patients with decompensated extreme hemodynamic balance its effects were evaluated by administering to patients with cirrhosis and ascites, with varying degrees of decompensation. Methods: We performed a prospective analysis of twenty patients, ten with cirrhosis and ascites and ten with spontaneous bacterial peritonitis. A control group of ten subjects was studied too. All groups underwent measurement of blood pressure, and blood and urine tests, pre and post treatment with propranolol. Results: Significant difference (p<0.04) was observed in urinary sodium between total patients without treatment and control group. The Rate of Sodium Reabsorption was significant between compensated patients and those with SBP, (p<0.04) before treatment. Patients without SBP pre and post treatment showed also, however, there was no significant difference between patients with SPB although there was a tendency to decrease sodium excretion. Low Mean arterial pressure, factor of poor prognosis in these patients showed positive correlation with low urinary sodium excretion in Child C patients with SBP post treatment. Conclusions: Patients with liver and extensive degree of hemodynamic decompensation are susceptible of renal impairment.

Research progress in role of nuclear factor E2-related factor2 in regulating development of cirrhotic portal hypertension / 中华肝胆外科杂志

Cirrhotic portal hypertension is associated with both increased intrahepatic vascular resistance and hyperdynamic circulation.These two pathogical changes of portal hypertension can be contributed to the unusually high or unusually low levels of vasodilator in liver and splanchnic organs.Vascular hyporesponsiveness due to reactive oxygen species is also a key factor which accounts for portal hemodynamic abnormalities.Transcription factor nuclear factor E2-related factor 2 (Nrf2),known by its role in anti-oxygenation,can initiate and enhance transcription of antioxidant response element (ARE) when exposure to oxidative stress occures.Related influence on expression of nitric oxide,carbon monoxide and their coenzymes has also been demonstrated for decades.The potential clinical significance will be unfolded if changes of Nrf2 expression,as well as the way modulating Nrf2,are found in cirrhotic portal hypertension.

Disfunción cardiaca en la cirrosis hepática / Cardiac dysfunction in liver cirrhosis

Objetivo: determinar las alteraciones de la función cardiaca en las personas que padecen cirrosis hepática. Métodos: se desarrolló un estudio descriptivo transversal en el Instituto de Gastroenterología durante el período 2011-2012, en 33 cirróticos de causa viral y alcohólica, 57,6 por ciento del sexo masculino, con una edad promedio de 50 años, la mayoría (84,8 por ciento) tenía la enfermedad compensada. Resultados: la disfunción diastólica fue la alteración cardiaca más frecuente (39,3 por ciento) seguida de la prolongación del intervalo QT (12,1 por ciento), disfunción sistólica (6,1 por ciento) y miocardiopatía cirrótica (3 por ciento). No se identificaron rasgos distintivos epidemiológicos y/o clínicos que caracterizara a estos pacientes. La circulación hiperdinámica fue más evidente en los que presentaron disfunción diastólica y en la cirrosis de origen alcohólico; las dimensiones cardiacas fueron normales en todos los casos. Conclusiones: las personas que padecen cirrosis son susceptibles de presentar alteraciones de la función cardiaca, incluso, desde la etapa compensada de la enfermedad, lo que debe considerarse por las implicaciones terapéuticas que demanda este tipo de paciente...

Objective: to determine abnormalities of cardiac function in subjects with liver cirrhosis. Methods: a descriptive cross-sectional study was conducted at the Institute of Gastroenterology from 2011 to 2012, in 33 cirrhotic patients due to alcoholic and viral causes, 57.6 percent male, with an average age of 50 years, most (84,8 percent) had compensated disease. Results: diastolic dysfunction was the most common cardiac disorders (39.3 percent) followed by QT prolongation (12.1 percent), systolic dysfunction (6.1 percent) and cirrhotic (3 percent) cardiomyopathy interval. No distinctive epidemiological and/or clinical studies were identified to characterize these patients. The hyperdynamic circulation was more evident in those presenting diastolic dysfunction and alcohol-related cirrhosis. Cardiac dimensions were normal in all cases. Conclusions: people with cirrhosis are susceptible to alterations in cardiac function, even from the compensated stage of the disease, which should be considered by the therapeutic implications of this type of patient demand...

The mechanism about the role of RhoA/ROCK singal pathway in portal hypertension / 中华肝胆外科杂志

The hepatic portal system is a unique circulatory system that connects two systems of capillary beds ; one in the wall of the small intestine and spleen and the second in the sinusoidal area of the liver.Therefore,alterations in vasoreactivity (vasodilation and vasoconstriction) play a critical role in the pathophysiology of portal hypertension (PHT).The RhoA/ ROCK pathway exerts an important role in the Ca2+-independent mechanism in vascular smooth muscle (VSM).This mechanism not only modulates the constriction of intrahepatic small vessels and hepatic stellate cells (HSCs) but also effects the hyperdynamic circulation due to vascular hyporesponsiveness.Understanding the detailed mechanism and role of the RhoA/ROCK signal pathway in portal hypertension could be of great utility in providing a new target for portal hypertension therapy.

The role of reactive oxygen species in the hyperdynamic circulation of cirrhotic portal hypertension / 中华肝胆外科杂志

Oxidative stress is involved in cirrhotic portal hypertension and a close relationship exists between oxidative stress and hyperdynamic circulation.This article elaborates on the function of various reactive oxygen species (e.g.,superoxide anion and hydrogen peroxide) and corresponding anti-oxidants (e.g.,NAD(P) H oxidase inhibitor,the scavengers of superoxide anion,hydrogen peroxide,and vitamin C or E) on the occurrence and development of hyperdynamic circulation in cirrhotic portal hypertension.We observed that the level of reactive oxygen species in cirrhotic portal hypertension was elevated over normal.The potential clinical value is that inhibition or removal of these reactive oxygen species can relieve hyperdynamic circulation and reduce complications for cirrhotic portal hypertension.

Ruptured Sinus of Valsalva Masquerading as Rheumatic Heart Disease.

Ruptured sinus of Valsalva is a rare lesion in pediatric age group. We are reporting a twelve year old child with hyperdynamic circulation being diagnosed and treated as Rheumatic heart disease.

Hemodynamic alterations in cirrhosis and portal hypertension / 대한간학회지

Portal hypertension (PHT) is associated with hemodynamic changes in intrahepatic, systemic, and portosystemic collateral circulation. Increased intrahepatic resistance and hyperdynamic circulatory alterations with expansion of collateral circulation play a central role in the pathogenesis of PHT. PHT is also characterized by changes in vascular structure, termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. Angiogenesis, the formation of new blood vessels, also occurs with PHT related in particular to the expansion of portosystemic collateral circulation. The complementary processes of vasoreactivity, vascular remodeling, and angiogenesis represent important targets for the treatment of portal hypertension. Systemic and splanchnic vasodilatation can induce hyperdynamic circulation which is related with multi-organ failure such as hepatorenal syndrome and cirrhotic cadiomyopathy.

Update on the treatment of portal hypertension / 대한내과학회지

Portal hypertension is responsible for most of the complications associated with liver cirrhosis, including variceal hemorrhage, ascites, and hepatic encephalopathy. It has become clear that a decrease in portal pressure can prevent or manage these serious complications. Until now, the pharmacotherapy of portal hypertension has focused on agents that reduce splanchnic blood flow, such as non-selective beta blockers and splanchnic vasoconstrictors. However, recent advances in the knowledge of the pathophysiology of portal hypertension have directed future treatment towards modulating the increased intrahepatic vascular resistance, in addition to managing the splanchnic circulation. Consequently, agents that modulate either the hyperdynamic circulation or angiogenesis are new therapeutic targets for managing portal hypertension. Several have been developed or are under investigation. To incorporate these pharmacologic approaches into clinical practice, data on patient-oriented outcomes are needed.

Hyperdynamic Circulation in Patients with Liver Cirrhosis and Portal Hypertension / 대한소화기학회지

Hyperdynamic circulation in patients with liver cirrhosis is characterized by increased cardiac output and heart rate, and decreased systemic vascular resistance with low arterial blood pressure and currently focused on understanding the pathogenesis because of possibility of developing novel treatment modality. Basically, these hemodynamic alternations arise from portal hypertension. Portosystemic collaterals develop to counterbalance the increased intrahepatic vascular resistance to portal blood flow and induce an increase in venous return to heart. Increased shear stress in vascular endothelial cell related high blood flow by portosystemic shunting contributes to this up-regulation of eNOS resulting in NO overproduction. Additionally, bypassing through portosystemic collaterals and escaping degradation of over-produced circulating vasodilators in the diseased liver can promote the peripheral arterial vasodilation. Vasodilation of the systemic and splanchnic circulations lead to a reduced systemic vascular resistance, and increased cardiac output and splanchnic blood flow. Furthermore, neurohumoral vasoconstrictive systems including systemic nervous system, rennin angiotensin aldosterone system, and vasopressin are intensively activated secondary to vasodilation. However, hyperdynamic circulation would be more aggravated by the activated vasoconstrictive systems. With the progression of the cirrhotic process, hyperdynamic alternations can be more profound due to hyporesponsiveness to vasoconstrictors and increased shunt formation in conjunction with autonomic neuropathy. Eventually, splanchnic arterial vasodilation results in an increase portal venous inflow, maintaining the elevated portal venous pressure. Hyperdynamic circulation is intimately involved in portal hypertension with liver cirrhosis, therefore it is reasonable to have an interest in complete understanding of the pathogenensis of hyperdynamic circulation to develop novel treatment modality.

Pathophysiology and diagnosis of portal hypertension / 대한내과학회지

Portal hypertension (PHT) as a consequence of liver cirrhosis is responsible for serious complications such as variceal bleeding, ascites and hepatic encehphalopathy. PHT is caused by increased intrahepatic vascular resistance and maintained by increased portal venous inflow. Increased intrahepatic vascular resistance has some reversible dynamic components related with activated hepatic stellate cell(HSC) and vacular activation mediators, therefore which come into the spotlight as new targets in treatment of PHT. PHT also induces hyperdynamic circulation by reduced systemic vascular resistance (SVR) and increased cardiac output. The gold-standard method for assessing the severity of PHT is a measurement of the hepatic venous pressure gradient (HVPG). However it is invasive, so non-invasive methods such as Doppler ultrasonography is under investigation as additive method.

Influence of cyclooxygenase inhibitor on expression of nitric oxide synthase in rats with portal hypertension / 上海第二医科大学学报

Objective To determine the mechanism of nitric oxide synthase(NOS) and prostacyclin(PGI2) acting on splanchnic hyperdynamic circulation of portal hypertention(PHT). Methods Ninety-six Sprague-Dawley rats were divided into three groups, namely, intrahepatic portal hypertension(IHPH, n=31), prehepatic portal hypertension(PHPH, n=33) and sham-operated controls(SO, n=32). Animals of each group were received indomethacin(INDO) either on a short term or long term with saline as control. Portal venous pressure, together with the concentration of nitric oxide (NO) and PGI2 in serum was measured. The constitutive nitric oxide synthase(cNOS)and inducible nitric oxide synthase(iNOS)activity in the abdominal aorta and small intestine of these rats were detrmined by spectrophotometry method. RT-PCR was performed to measure the levels of iNOS and cNOS mRNA in the arteries and guts mentioned above. Results Although INDO decreased the concentration of PGI2 in serum, the long-term INDO-treated group restored splanchnic hyperdynamic circulation in both IHPH and PHPH rats, concomitant with enhanced expression of iNOS and concentration of NO(P0.05). Conclusion Overproduction of NO inducing hemodynamic abnormalities of PHT is synthesized principally by increase of iNOS. There may be a possible interaction between PGI2 and NO in hyperhemodynamics of PHT, while PGI2 may not be a mediator in the formation and development of hyperdynamic circulatory state.

Patogénesis de la hipertensión portal / Pathogenesis of portal hypertension

It is now well established that portal hypertension is not a purely mechanical phenomenon. Primary hemodynamic alterations develop in the hepatic and systemic circulatory systems; these alterations in combination with mechanical factors contribute to the development of portal hypertension. In the hepatic circulation, these hemodynamic alterations are characterized by vasoconstriction and impaired hepatic vasodilatory responses, whereas in the systemic circulation, particularly in the splanchnic bed, vessels are hyperemic with increased flow. Thus, an increase in intrahepatic resistance in conjunction with increased portal venous inflow, mediated through splanchnic dilation, contributes to the development of portal hypertension. The ensuing development of elevated flow and transmural pressure through collateral vessels from the hypertensive portal vasculature into the lower pressure systemic venous circulation accounts for many of the complications, such as bleeding esophageal varices, observed with portal hypertension. The importance of the primary vascular origin of portal hypertension is emphasized by the utility of current therapies aimed at reversing these hemodynamic alterations, such as nitrates, which reduce portal pressure through direct intrahepatic vasodilatation, and fi blockers and octreotide, which reduce splanchnic vasodilatation and portal venous inflow. New evidence concerning relevant molecular mechanisms of contractile signaling pathways in hepatic stellate cells and the complex regulatory pathways of vasoactive molecules in liver endothelial cells makes a better understanding of these processes essential for developing further experimental therapies for portal hypertension. This article examines the current concepts relating to cellular mechanism that underlie the hemodynamic alterations that characterize and account for the development of portal hypertension.

Actualmente está bien establecido que la hipertensión portal no es un fenómeno puramente mecánico. En esta entidad se presentan alteraciones hemodinámicas primarias en los sistemas circulatorios hepático y sistémico; estas alteraciones en combinación con factores mecánicos, contribuyen al desarrollo de la hipertensión portal. En la circulación hepática, las alteraciones hemodinámicas se caracterizan por vasoconstricción y una respuesta anómala a la vasodilatación, mientras que en la circulación sistémica, especialmente en el lecho esplácnico, los vasos están congestivos y con un flujo aumentado. Por lo tanto un incremento en las resistencias intrahepáticas asociado a un aumento del flujo venoso portal, mediado a través de la dilatación esplácnica, contribuyen al desarrollo de la hipertensión portal. La consecuencia del flujo y la presión transmural elevada a través de los vasos colaterales a partir de una vasculatura portal hipertensa hacia la circulación venosa sistémica con menor presión, conlleva a muchas de las complicaciones observadas en la hipertensión portal, como la hemorragia por várices esofágicas. La importancia del origen vascular primario de la hipertensión portal se basa en la utilidad de terapias actuales orientadas a revertir estas alteraciones hemodinámicas, como los nitratos que reducen la presión portal, a través de vasodilatación intrahepática directa y los P bloqueadores y octreótida, que reducen la vasodilatación esplácnica y el flujo venoso portal. Además, existen nuevas evidencias en relación con los mecanismos moleculares de vías de señalización contráctil de las células estelares hepáticas y complejas vías de regulación de sustancias vasoactivas en las células endoteliales hepáticas que han ayudado a entender mejor estos procesos esenciales para el desarrollo de terapias experimentales para la hipertensión portal. Este artículo revisa los conceptos actuales relacionados con los mecanismos celulares causales de las alteraciones hemodinámicas que caracterizan y condicionan el desarrollo de la hipertensión portal.

Preliminary study of Glytan on treating portal hypertension rats induced by biliary liver fibrosis / 中华中医药杂志

Objective: To investigate the mechanism of Glytan lowering portal pressure induced by biliary liver fibrosis. Methods: SD male rats, 240-260g weight around, were randomly divided into sham-operation group, model group, propranolol group, Glytan high-dose, middle-dose and low-dose group according to the weight. Portal hypertension was induced by common bile duct ligation in rats. After two and four weeks, measured the portal pressure(PP) of each group, observed the histological changes of liver by HE staining, tested liver function and the concentration of endothelin-1 in systemic circulation and mesenteric circulation radioimmnuoassay. Results: After two and four weeks, portal pressure of model group rats increased significantly. Both Glytan and propranolol can decrease PP after two and four weeks, and the pressure-relief effect was similar between the two drugs. HE staining showed that Glytan can significantly inhibit the formation of collagen, promote the recovery of liver tissue structure; liver function indicated a significant decrease in serum AST, ALT, TBIL and Na+ concentration. In addition, Glytan decreased the concentration of endothelin -1 in systemic circulation, increased it in mesenteric circulation after two weeks. Conclusion: Glytan decrease PP by improving liver function and microcirculation, inhibiting collagen formation and water-sodium retention after long-term therapy, ameliorating hyperdynamic circulation at the early stage.

Relationship between plasma carbon monoxide and hyperdynamic circulation of cirrhotic rats / 中华消化杂志

Objective To explore the relationship between the plasma level of carbon monoxide and the hyperdynamic circulation of cirrhotic rats. Methods S.D. rats were divided into cirrhotic ( n =10) and control ( n =10) groups. Liver cirrhosis was induced by percutaneous administration of carbon tetrachloride. Mean arterial pressure (MAP, kPa),heart rate (HR,beat/min) and portal pressure (PP,cm H 2O) were measured by indwelling catheters. Plasma CO was measured by Chalmers method, and plasma NO 2/NO 3 was determined by the reduction of cadmium column. Heme oxygenase (HO) activity in splanchnic organs from cirrhotic rats and controls was also determined. Results Typical features of cirrhosis were histologically observed in carbon tetrachloride treated animals. The cirrhotic group presented a significant increase in plasma CO [( 18.69 ? 1.86 )?mol/L vs. ( 10.27 ? 1.21 )?mol/L, P

The Effects of Nitric Oxide Inhibitor on Hyperdynamic Circulation in Portal Hypertensive Rats / 영남의대학술지

BACKGROUND: Nitric oxide, a vasodilator synthesized from L-arginine by vascular endothelial cells. accounts for the biological activity of endothelium derived relaxing factor. Previous studies demonstrated that nitric oxide inhibitor. N'-Nitro-L-Arginine(NNA)diminished the hyperdynamic splanchnic and systemic circulation in portal hypertensive rats. The present study was done to determine the role of nitric oxide in the development of hyperdynamic circulations in the prehepatic portal hypertensive rat model produced by partial portal vein ligation. METHODS: The portal hypertensive rats were divided into water ingestion group and NNA ingestion group. After partial portal vein ligation. NNA ingestion group and water ingestion group received NNA, 1mg/kg/day and plain water through the mouth for 14 days, respectively. Cardiac output, mean arterial pressure, organ blood flow and porto-systemic shunting were measured by radioisotope microsphere methods. Vascular resistances were calculated by standard equation. RESULTS: There were significant decreases in mean arterial pressure, increases in cardiac output and cardiac index, and decreases in total systemic and splanchnic vascular resistance in portal hypertensive rats compared to normal control froup(p<0.01). Compared to the water ingestion group, significantly increased mean arterial pressure wit decreased cardiac output and cardiac index were dexeloped in the NNA ingestion group. Total systemic and splanchnic vascular resistance were significantly increased in the NNA ingestion group compared to water ingestion group(p<0.05). But, there was no significant difference in portal pressure between the two groups. CONCLUSION: The hemodynamic results of this study indicate that hyperdynamic circulation in prehepatic portal hypertensive rat model was attenuated by ingestion of NNA. Nitric oxide may play an important role in the development of hyperdynamic circulation with splanchnic vaodilation in chronic portal hypertension.

Hemodynamic Properties of Portal Hypertansion in a Portal Vein Stenotic Rat Model / 대한내과학회지

OBJECTIVES: Hemodynamic measurements of chronic portal hypertension were done to study the mechanisms that maintain high portal pressure despite well developed collateral circulations. METHODS: A prehepatic portal hypertensive rat model was produced by partial portal vein ligation. Cardiac output, organ blood flow and porto-systemic shunt were measured by radioisotope labeled microsphere methods, and vascular resistance was calculated by standard equation. RESULTS: There was a significant reduction in the weight of the liver and increase in the weight of the spleen in the portal stenotic rats. Porto-systemic shunting, representing development of the collateral circulations, was 96.7+/-0.6% in the portal stenosis group compared with 0.9+/-0.2% in the control group (p0.05). CONCLUSION: The hemodynamic results of this study indicate that hyperdynamic status of systemic and splanchnic circulation was present in chronic portal hypertension and that the primary factor contributing to the persistently elevated portal venous pressure was the markedly increased portal venous inflow.