Cardiovascular abnormalities accompany both portal hypertension and cirrhosis. These consist of hyperdynamic circulation, defined as reduced mean arterial pressure and systemic vascular resistance, and increased cardi...Cardiovascular abnormalities accompany both portal hypertension and cirrhosis. These consist of hyperdynamic circulation, defined as reduced mean arterial pressure and systemic vascular resistance, and increased cardiac output. Despite the baseline increased cardiac output, ventricular inotropic and chronotropic responses to stimuli are blunted, a condition known as cirrhotic cardiomyopathy. Both conditions may play an initiating or aggravating pathogenic role in many of the complications of liver failure or portal hypertension including ascites, variceal bleeding, hepatorenal syndrome and increased postoperative mortality after major surgery or liver transplantation. This review briefly examines the major mechanisms that may underlie these cardiovascular abnormalities, concentrating on nitric oxide, endogenous cannabinoids, central neural activation and adrenergic receptor changes. Future work should address the complex interrelationships between these systems.展开更多
Cardiac dysfunction is frequently observed in patients with cirrhosis, and has long been linked to the direct toxic effect of alcohol. Cirrhotic cardiomyopathy(CCM) has recently been identified as an entity regardless...Cardiac dysfunction is frequently observed in patients with cirrhosis, and has long been linked to the direct toxic effect of alcohol. Cirrhotic cardiomyopathy(CCM) has recently been identified as an entity regardless of the cirrhosis etiology. Increased cardiac output due to hyperdynamic circulation is a pathophysiological hallmark of the disease. The underlying mechanisms involved in pathogenesis of CCM are complex and involve various neurohumoral and cellular pathways, including the impaired β-receptor and calcium signaling, altered cardiomyocyte membrane physiology, elevated sympathetic nervous tone and increased activity of vasodilatory pathways predominantly through the actions of nitric oxide, carbon monoxide and endocannabinoids. The main clinical features of CCM include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities and chronotropic incompetence. Particularly the diastolic dysfunction with impaired ventricularrelaxation and ventricular filling is a prominent feature of CCM.The underlying mechanism of diastolic dysfunction in cirrhosis is likely due to the increased myocardial wall stiffness caused by myocardial hypertrophy,fibrosis and subendothelial edema,subsequently resulting in high filling pressures of the left ventricle and atrium.Currently,no specific treatment exists for CCM.The liver transplantation is the only established effective therapy for patients with end-stage liver disease and associated cardiac failure.Liver transplantation has been shown to reverse systolic and diastolic dysfunction and the prolonged QT interval after transplantation.Here,we review the pathophysiological basis and clinical features of cirrhotic cardiomyopathy,and discuss currently available limited therapeutic options.展开更多
In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, m...In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesen- teric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes alsoseem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.展开更多
AIM: To investigate the systemic hemodynamic effects of two surgical procedures largely employed for treatment of schistosomal portal hypertension. METHODS: Thirty-six patients undergoing elective surgical treatment o...AIM: To investigate the systemic hemodynamic effects of two surgical procedures largely employed for treatment of schistosomal portal hypertension. METHODS: Thirty-six patients undergoing elective surgical treatment of portal hypertension due to hepatosplenic mansonic schistosomiasis were prospectively evaluated. All patients were subjected to preoperative pulmonary artery catheterization; 17 were submitted to esophagogastric devascularization and splenectomy (EGDS) and 19 to distal splenorenal shunt (DSRS). The systemic hemodynamic assessment was repeated 4 d after the surgical procedure. RESULTS: Preoperative evaluation revealed (mean ± SD) an increased cardiac index (4.78 ± 1.13 L/min per m2),associated with a reduction in systemic vascular resistance index (1457 ± 380.7 dynes.s/cm5.m2). The mean pulmonary artery pressure (18 ± 5.1 mmHg) as well as the right atrial pressure (7.9 ± 2.5 mmHg) were increased,while the pulmonary vascular resistance index (133 ± 62 dynes.s/cm5.m2) was decreased. Four days after EGDS,a significant reduction in cardiac index (3.80 ± 0.4 L/min per m2,P < 0.001) and increase in systemic vascular resistance index (1901.4 ± 330.2 dynes.s/cm5. m2,P < 0.001) toward normal levels were observed. There was also a significant reduction in pulmonary artery pressure (12.65 ± 4.7 mmHg,P < 0.001) and no significant changes in the pulmonary vascular resistance index (141.6 ± 102.9 dynes.s/cm5.m2). Four days after DSRS,a non-significant increase in cardiac index (5.2 ± 0.76 L/min per m2) and systemic vascular resistance index (1389 ± 311 dynes.s/cm5.m2) was observed. There was also a non-significant increase in pulmonary artery pressure (19.84 ± 5.2 mmHg),right cardiac work index (1.38 ± 0.4 kg.m/m2) and right ventricular systolic work index (16.3 ± 6.3 g.m/m2),without significant changes in the pulmonary vascular resistance index (139.7 ± 67.8 dynes.s/cm5.m2). CONCLUSION: The hyperdynamic circulatory state observed in mansonic schistosomiasis was corrected by EGDS,but was maintained展开更多
AIM： To investigate the interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy by observing splenic arterial and venous pathological changes and the role of extracell...AIM： To investigate the interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy by observing splenic arterial and venous pathological changes and the role of extracellular matrix in the pathogenesis of portal hypertensive vasculopathy by measuring the expression of type Ⅰ and type Ⅲ procollagen mRNA in splenic venous walls of portal hypertensive patients. METHODS： Morphological changes of splenic arteries and veins taken from portal hypertensive patients （n = 20） and normal controls （n = 10） were observed under optical and electron microscope. Total RNA was extracted and the expression of type Ⅰ and type Ⅲ procollagen mRNA in splenic venous walls of portal hypertensive patients （n= 20） was semi-quantitatively detected using reverse transcription-polymerase chain reaction （RT-PCR）. RESULTS： Under optical microscope, splenic arterial intima was destroyed and internal elastic membrane and medial elastic fibers of the splenic arterial walls were degenerated and broken. Splenic venous intima became remarkably thick. Endothelial cells were not intact with formation of mural thrombus. The tunica media became thickened significantly due to hypertrophy of smooth muscles. Fibers and connective tissues were increased obviously. Under electron microscope, smooth muscle cells of the splenic arteries were degenerated and necrotized. Phenotypes of smooth muscle cells changed from constrictive into synthetic type. Red blood cells and platelets accumulated around the damaged endothelial cells. Synthetic smooth muscle cells were predominant in splenic veins and their cytoplasma had plentiful rough endoplasmic reticulum ribosomes and Golgi bodies. Along the vascular wall, a lot of collagen fibers were deposited, the intima was damaged and blood components accumulated. There was no significant difference in the expression of type Ⅰ procollagen mRNA in splenic venous wall between the patients with portal hypertension and those without portal hypertension展开更多
BACKGROUND: Nitric oxide (NO) and prostacyclin (PGI(2)) are both powerful vasoactive substances correlated with the hyperhemodynamics of portal hypertension (PHT), a common syndrome characterized by a pathological inc...BACKGROUND: Nitric oxide (NO) and prostacyclin (PGI(2)) are both powerful vasoactive substances correlated with the hyperhemodynamics of portal hypertension (PHT), a common syndrome characterized by a pathological increase in portal venous pressure. The purpose of the present study was to evaluate the possible interaction between these two endothelial vasodilators, together with their respective roles in the hyperdynamic splanchnic circulation of PHT. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into three groups: intrahepatic portal hypertension (IHPH) induced by injection of CCI4 (n=31), prehepatic portal hypertension (PHPH) induced by partial stenosis of the portal vein (n=33), and sham-operated controls (SO) (n=32). Animals of each group received indomethacin (INDO), a cyclooxygenase (COX) inhibitor, either short-term (7 days) or long-term (15 days), with saline as control. Free portal pressure (FPP), together with the concentration of NO and PGI(2) in serum were measured. The activity of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) in the abdominal aorta and small intestine were determined by spectrophotometry. RT-PCR was performed to measure the levels of cNOS and iNOS mRNA in the arteries and small intestines. RESULTS: Compared with SO rats, the concentrations of NO and PGI(2) in PHT rats were elevated, which were consistent with the increased FPP (P<0.05). Although administration of INDO persistently decreased the concentration of PGI(2) in serum (P<0.05), the long-term INDO-treated IHPH and PHPH groups had restored splanchnic hyperdynamic circulation, demonstrated by the enhanced FPP (P<0.05). Furthermore, the changes of dynamic circulatory state in both IHPH and PHPH rats were concomitant with the expression and activity of iNOS and the concentration of NO (P<0.05). Although the expression and activity of cNOS in abdominal aorta of PHT rats were higher than in SO rats (P<0.05), there was no difference in small intestinal tissues between PHT a展开更多
AIM:To evaluate the effects of estrogen(E2) on systemic and splanchnic hyperdynamic circulation in portal hypertensive rats.METHODS:Fifty castrated female Sprague-Dawley rats were divided into five groups:sham operati...AIM:To evaluate the effects of estrogen(E2) on systemic and splanchnic hyperdynamic circulation in portal hypertensive rats.METHODS:Fifty castrated female Sprague-Dawley rats were divided into five groups:sham operation(SO),partial portal vein ligation(PPVL) + placebo(PLAC),PPVL + E2,PPVL + ICI and PPVL + E2 + ICI. Hemodynamic measurements were performed using ultrasonography. Mesenteric arteriole contractility in response to norepinephrine was determined using a vessel perfusion system. Oxidative stress in the mesenteric artery was investigated by in situ detection of the superoxide anion(O2) and hydrogen peroxide(H2O2) concentrations.RESULTS:Treatment with E2 resulted in a significant decrease of portal pressure(P < 0.01) and portal venous inflow(P < 0.05),and higher systemic vascular resistance(P < 0.05) and splanchnic arteriolar resistance(P < 0.01) in PPVL + E2 rats compared to PPVL+ PLAC rats. In the mesenteric arterioles of PPVL +E2 rats,the dose-response curve was shifted left,and the EC50was decreased(P < 0.01). E2 reduced O2 production and H2O2concentration in the mesenteric artery. However,ICI182,780 reversed the beneficial effects of E2,therefore,the systemic and splanchnic hyperdynamic circulation were more deteriorated in ICI182,780-treated rats.CONCLUSION:Treatment with estrogen improved the systemic and splanchnic hyperdynamic circulation in PPVL rats,in part due to the alleviation of oxidative stress.展开更多
BACKGROUND Portal hypertension(PH)is associated with changes in vascular structure and function of the portosplenomesenteric system(PSMS).This is referred to as portal hypertensive vasculopathy.Pathological abnormalit...BACKGROUND Portal hypertension(PH)is associated with changes in vascular structure and function of the portosplenomesenteric system(PSMS).This is referred to as portal hypertensive vasculopathy.Pathological abnormalities of PSMS has been described in the literature for cirrhotic patients.Raised portal pressure and hyperdynamic circulation are thought to be the underlying cause of this vasculopathy.In view of this,it is expected that pathological changes in splenic and portal vein similar to those reported in cirrhotic patients with PH may also be present in patients with non-cirrhotic PH(NCPH).AIM To investigate pathological abnormalities of splenic vein in patients with NCPH,and suggest its possible implications in the management of PH.METHODS A prospective observational study was performed on 116 patients with NCPH[Extrahepatic portal vein obstruction(EHPVO):53 and non-cirrhotic portal fibrosis(NCPF):63]who underwent proximal splenorenal shunt(PSRS),interposition shunt or splenectomy with devascularization in JIPMER,Pondicherry,India,a tertiary level referral center,between 2011-2016.All patients were evaluated by Doppler study of PSMS,computed tomography portovenogram and upper gastrointestinal endoscopy.An acoustic resonance forced impulse(ARFI)scan and abdomen ultrasound were done for all cases to exclude cirrhosis.Intraoperative and histopathological assessment of the harvested splenic vein was performed in all.The study group was divided into delayed and early presentation based on the median duration of symptoms(i.e.108 mo).RESULTS The study group comprising of 116 patients[77(66%)females and 39(34%)males]with NCPH had a median age of 22 years.Median duration of symptoms was 108 mo.The most common presentation in both EHPVO and NCPF patients was upper gastrointestinal bleeding(hematemesis and melena).The ARFI scan revealed a median score of 1.2(1.0-1.8)m/s for EHPVO and 1.5(0.9-2.8)m/s for NCPF.PSRS was performed in 84 patients(two of whom underwent interposition PSRS using a 10 mm Dacron graft);splenoadr展开更多
Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a...Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.展开更多
Portal hypertension, one of the vascular diseases, not only has lesions in liver, but also changes in vascular structures and functions of extrahepatic portal system, systemic system and pulmonary drculation. The pabh...Portal hypertension, one of the vascular diseases, not only has lesions in liver, but also changes in vascular structures and functions of extrahepatic portal system, systemic system and pulmonary drculation. The pabhological changes of vasculopathy in portal hypertension include remodeling of arterialized visceral veins, intimal injury of visceral veins and destruction of contractile structure in visceral arterial wall. The mechanisms of vasculopathy in portal hypertension may be attributed to the changes of hemodynamics in portal system, immune response, gene modulation, vasoactive substances, and intrahepatic blood flow resistance. Portal hypertension can cause visceral hyperdynamic circulation, and the development and progression of visceral vasculopathy, while visceral vasculopathy can promote the development and progression of portal hypertension and visceral hyperdynamic circulation in turn. The aforementioned three factors interact in the pathogenesis of hepatic cirrhosisinduced portal hypertension and are involved in hemorrhage due to varicose vein rupture.展开更多
文摘Cardiovascular abnormalities accompany both portal hypertension and cirrhosis. These consist of hyperdynamic circulation, defined as reduced mean arterial pressure and systemic vascular resistance, and increased cardiac output. Despite the baseline increased cardiac output, ventricular inotropic and chronotropic responses to stimuli are blunted, a condition known as cirrhotic cardiomyopathy. Both conditions may play an initiating or aggravating pathogenic role in many of the complications of liver failure or portal hypertension including ascites, variceal bleeding, hepatorenal syndrome and increased postoperative mortality after major surgery or liver transplantation. This review briefly examines the major mechanisms that may underlie these cardiovascular abnormalities, concentrating on nitric oxide, endogenous cannabinoids, central neural activation and adrenergic receptor changes. Future work should address the complex interrelationships between these systems.
文摘Cardiac dysfunction is frequently observed in patients with cirrhosis, and has long been linked to the direct toxic effect of alcohol. Cirrhotic cardiomyopathy(CCM) has recently been identified as an entity regardless of the cirrhosis etiology. Increased cardiac output due to hyperdynamic circulation is a pathophysiological hallmark of the disease. The underlying mechanisms involved in pathogenesis of CCM are complex and involve various neurohumoral and cellular pathways, including the impaired β-receptor and calcium signaling, altered cardiomyocyte membrane physiology, elevated sympathetic nervous tone and increased activity of vasodilatory pathways predominantly through the actions of nitric oxide, carbon monoxide and endocannabinoids. The main clinical features of CCM include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities and chronotropic incompetence. Particularly the diastolic dysfunction with impaired ventricularrelaxation and ventricular filling is a prominent feature of CCM.The underlying mechanism of diastolic dysfunction in cirrhosis is likely due to the increased myocardial wall stiffness caused by myocardial hypertrophy,fibrosis and subendothelial edema,subsequently resulting in high filling pressures of the left ventricle and atrium.Currently,no specific treatment exists for CCM.The liver transplantation is the only established effective therapy for patients with end-stage liver disease and associated cardiac failure.Liver transplantation has been shown to reverse systolic and diastolic dysfunction and the prolonged QT interval after transplantation.Here,we review the pathophysiological basis and clinical features of cirrhotic cardiomyopathy,and discuss currently available limited therapeutic options.
基金Supported by the Grants from the Ministerio de Educacióny Ciencia, No. SAF2006-0314the Ministerio de Cienciae Innovación, No. SAF2009-08354
文摘In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesen- teric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes alsoseem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.
文摘AIM: To investigate the systemic hemodynamic effects of two surgical procedures largely employed for treatment of schistosomal portal hypertension. METHODS: Thirty-six patients undergoing elective surgical treatment of portal hypertension due to hepatosplenic mansonic schistosomiasis were prospectively evaluated. All patients were subjected to preoperative pulmonary artery catheterization; 17 were submitted to esophagogastric devascularization and splenectomy (EGDS) and 19 to distal splenorenal shunt (DSRS). The systemic hemodynamic assessment was repeated 4 d after the surgical procedure. RESULTS: Preoperative evaluation revealed (mean ± SD) an increased cardiac index (4.78 ± 1.13 L/min per m2),associated with a reduction in systemic vascular resistance index (1457 ± 380.7 dynes.s/cm5.m2). The mean pulmonary artery pressure (18 ± 5.1 mmHg) as well as the right atrial pressure (7.9 ± 2.5 mmHg) were increased,while the pulmonary vascular resistance index (133 ± 62 dynes.s/cm5.m2) was decreased. Four days after EGDS,a significant reduction in cardiac index (3.80 ± 0.4 L/min per m2,P < 0.001) and increase in systemic vascular resistance index (1901.4 ± 330.2 dynes.s/cm5. m2,P < 0.001) toward normal levels were observed. There was also a significant reduction in pulmonary artery pressure (12.65 ± 4.7 mmHg,P < 0.001) and no significant changes in the pulmonary vascular resistance index (141.6 ± 102.9 dynes.s/cm5.m2). Four days after DSRS,a non-significant increase in cardiac index (5.2 ± 0.76 L/min per m2) and systemic vascular resistance index (1389 ± 311 dynes.s/cm5.m2) was observed. There was also a non-significant increase in pulmonary artery pressure (19.84 ± 5.2 mmHg),right cardiac work index (1.38 ± 0.4 kg.m/m2) and right ventricular systolic work index (16.3 ± 6.3 g.m/m2),without significant changes in the pulmonary vascular resistance index (139.7 ± 67.8 dynes.s/cm5.m2). CONCLUSION: The hyperdynamic circulatory state observed in mansonic schistosomiasis was corrected by EGDS,but was maintained
基金Supported by National Natural Science Foundation of China, No. A30170920
文摘AIM： To investigate the interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy by observing splenic arterial and venous pathological changes and the role of extracellular matrix in the pathogenesis of portal hypertensive vasculopathy by measuring the expression of type Ⅰ and type Ⅲ procollagen mRNA in splenic venous walls of portal hypertensive patients. METHODS： Morphological changes of splenic arteries and veins taken from portal hypertensive patients （n = 20） and normal controls （n = 10） were observed under optical and electron microscope. Total RNA was extracted and the expression of type Ⅰ and type Ⅲ procollagen mRNA in splenic venous walls of portal hypertensive patients （n= 20） was semi-quantitatively detected using reverse transcription-polymerase chain reaction （RT-PCR）. RESULTS： Under optical microscope, splenic arterial intima was destroyed and internal elastic membrane and medial elastic fibers of the splenic arterial walls were degenerated and broken. Splenic venous intima became remarkably thick. Endothelial cells were not intact with formation of mural thrombus. The tunica media became thickened significantly due to hypertrophy of smooth muscles. Fibers and connective tissues were increased obviously. Under electron microscope, smooth muscle cells of the splenic arteries were degenerated and necrotized. Phenotypes of smooth muscle cells changed from constrictive into synthetic type. Red blood cells and platelets accumulated around the damaged endothelial cells. Synthetic smooth muscle cells were predominant in splenic veins and their cytoplasma had plentiful rough endoplasmic reticulum ribosomes and Golgi bodies. Along the vascular wall, a lot of collagen fibers were deposited, the intima was damaged and blood components accumulated. There was no significant difference in the expression of type Ⅰ procollagen mRNA in splenic venous wall between the patients with portal hypertension and those without portal hypertension
基金a grant from the KeyBasic Research Program of Shanghai(No.034119922)
文摘BACKGROUND: Nitric oxide (NO) and prostacyclin (PGI(2)) are both powerful vasoactive substances correlated with the hyperhemodynamics of portal hypertension (PHT), a common syndrome characterized by a pathological increase in portal venous pressure. The purpose of the present study was to evaluate the possible interaction between these two endothelial vasodilators, together with their respective roles in the hyperdynamic splanchnic circulation of PHT. METHODS: Ninety-six male Sprague-Dawley rats were randomly divided into three groups: intrahepatic portal hypertension (IHPH) induced by injection of CCI4 (n=31), prehepatic portal hypertension (PHPH) induced by partial stenosis of the portal vein (n=33), and sham-operated controls (SO) (n=32). Animals of each group received indomethacin (INDO), a cyclooxygenase (COX) inhibitor, either short-term (7 days) or long-term (15 days), with saline as control. Free portal pressure (FPP), together with the concentration of NO and PGI(2) in serum were measured. The activity of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) in the abdominal aorta and small intestine were determined by spectrophotometry. RT-PCR was performed to measure the levels of cNOS and iNOS mRNA in the arteries and small intestines. RESULTS: Compared with SO rats, the concentrations of NO and PGI(2) in PHT rats were elevated, which were consistent with the increased FPP (P<0.05). Although administration of INDO persistently decreased the concentration of PGI(2) in serum (P<0.05), the long-term INDO-treated IHPH and PHPH groups had restored splanchnic hyperdynamic circulation, demonstrated by the enhanced FPP (P<0.05). Furthermore, the changes of dynamic circulatory state in both IHPH and PHPH rats were concomitant with the expression and activity of iNOS and the concentration of NO (P<0.05). Although the expression and activity of cNOS in abdominal aorta of PHT rats were higher than in SO rats (P<0.05), there was no difference in small intestinal tissues between PHT a
文摘AIM:To evaluate the effects of estrogen(E2) on systemic and splanchnic hyperdynamic circulation in portal hypertensive rats.METHODS:Fifty castrated female Sprague-Dawley rats were divided into five groups:sham operation(SO),partial portal vein ligation(PPVL) + placebo(PLAC),PPVL + E2,PPVL + ICI and PPVL + E2 + ICI. Hemodynamic measurements were performed using ultrasonography. Mesenteric arteriole contractility in response to norepinephrine was determined using a vessel perfusion system. Oxidative stress in the mesenteric artery was investigated by in situ detection of the superoxide anion(O2) and hydrogen peroxide(H2O2) concentrations.RESULTS:Treatment with E2 resulted in a significant decrease of portal pressure(P < 0.01) and portal venous inflow(P < 0.05),and higher systemic vascular resistance(P < 0.05) and splanchnic arteriolar resistance(P < 0.01) in PPVL + E2 rats compared to PPVL+ PLAC rats. In the mesenteric arterioles of PPVL +E2 rats,the dose-response curve was shifted left,and the EC50was decreased(P < 0.01). E2 reduced O2 production and H2O2concentration in the mesenteric artery. However,ICI182,780 reversed the beneficial effects of E2,therefore,the systemic and splanchnic hyperdynamic circulation were more deteriorated in ICI182,780-treated rats.CONCLUSION:Treatment with estrogen improved the systemic and splanchnic hyperdynamic circulation in PPVL rats,in part due to the alleviation of oxidative stress.
文摘BACKGROUND Portal hypertension(PH)is associated with changes in vascular structure and function of the portosplenomesenteric system(PSMS).This is referred to as portal hypertensive vasculopathy.Pathological abnormalities of PSMS has been described in the literature for cirrhotic patients.Raised portal pressure and hyperdynamic circulation are thought to be the underlying cause of this vasculopathy.In view of this,it is expected that pathological changes in splenic and portal vein similar to those reported in cirrhotic patients with PH may also be present in patients with non-cirrhotic PH(NCPH).AIM To investigate pathological abnormalities of splenic vein in patients with NCPH,and suggest its possible implications in the management of PH.METHODS A prospective observational study was performed on 116 patients with NCPH[Extrahepatic portal vein obstruction(EHPVO):53 and non-cirrhotic portal fibrosis(NCPF):63]who underwent proximal splenorenal shunt(PSRS),interposition shunt or splenectomy with devascularization in JIPMER,Pondicherry,India,a tertiary level referral center,between 2011-2016.All patients were evaluated by Doppler study of PSMS,computed tomography portovenogram and upper gastrointestinal endoscopy.An acoustic resonance forced impulse(ARFI)scan and abdomen ultrasound were done for all cases to exclude cirrhosis.Intraoperative and histopathological assessment of the harvested splenic vein was performed in all.The study group was divided into delayed and early presentation based on the median duration of symptoms(i.e.108 mo).RESULTS The study group comprising of 116 patients[77(66%)females and 39(34%)males]with NCPH had a median age of 22 years.Median duration of symptoms was 108 mo.The most common presentation in both EHPVO and NCPF patients was upper gastrointestinal bleeding(hematemesis and melena).The ARFI scan revealed a median score of 1.2(1.0-1.8)m/s for EHPVO and 1.5(0.9-2.8)m/s for NCPF.PSRS was performed in 84 patients(two of whom underwent interposition PSRS using a 10 mm Dacron graft);splenoadr
文摘Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.
基金Supported by the National Natural Science Foundation of China,No. A30170920
文摘Portal hypertension, one of the vascular diseases, not only has lesions in liver, but also changes in vascular structures and functions of extrahepatic portal system, systemic system and pulmonary drculation. The pabhological changes of vasculopathy in portal hypertension include remodeling of arterialized visceral veins, intimal injury of visceral veins and destruction of contractile structure in visceral arterial wall. The mechanisms of vasculopathy in portal hypertension may be attributed to the changes of hemodynamics in portal system, immune response, gene modulation, vasoactive substances, and intrahepatic blood flow resistance. Portal hypertension can cause visceral hyperdynamic circulation, and the development and progression of visceral vasculopathy, while visceral vasculopathy can promote the development and progression of portal hypertension and visceral hyperdynamic circulation in turn. The aforementioned three factors interact in the pathogenesis of hepatic cirrhosisinduced portal hypertension and are involved in hemorrhage due to varicose vein rupture.
