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 in patients who underwent DSRS. Similarly,the elevated mean pulmonary artery pressure was corrected after EGDS and maintained after DSRS. EGDS seems to be the most physiologic surgery for patients with schistosomal portal hypertension.展开更多
The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major componen...The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major component of the renin-angiotensin system (RAS). It mediates the classical biological actions of Ang II. Among the structures required for regulation and activation of the receptor, its carboxyl- terminal region plays crucial roles in receptor internalization, desensitization and phosphorylation. The mechanisms involved in heterotrimeric G-protein coupling to the receptor, activation of the downstream signaling pathway by G proteins and the Ang II signal transduction pathways leading to specific cellular responses are discussed. In addition, recent work on the identification and characterization of novel proteins associated with carboxy1-terminus of the AT1 receptor is presented. These novel proteins will advance our understanding of how the receptor is internalized and recycled as they provide molecular mechanisms for the activation and regulation of G-protein-coupled receptors.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 （P〉0.05）, but the expression of type Ⅲ procoagen mRNA was significantly stronger in the patients with portal hypertension than in those without portal hypertension （P〈 0.01）. CONCLUSION： Type Ⅲ procollagen and collagen might be important extra-cellular matrix resulting in neointimal formation and vascular remodeling in the pathogenesis of portal hypertensive vasculopathy. The pathological changes in splenic arteries and veins exist in portal hypertension patients. There might be an interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy.展开更多
AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley r...AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCI4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitro-L-arginine (L-NNA)group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1mL of saline, L-NNA (3.3 mg/kg-d) and INDO (5 mg/kg·d) respectively through gastric tubes for one week/then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α, a stable hydrolytic product of PGI2, was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGFla (pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats (1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11, 75.21±6.89) were significantly higher than those in SO rats (725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGFla and serum NO2/7NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto- concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.展开更多
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 in patients who underwent DSRS. Similarly,the elevated mean pulmonary artery pressure was corrected after EGDS and maintained after DSRS. EGDS seems to be the most physiologic surgery for patients with schistosomal portal hypertension.
文摘The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major component of the renin-angiotensin system (RAS). It mediates the classical biological actions of Ang II. Among the structures required for regulation and activation of the receptor, its carboxyl- terminal region plays crucial roles in receptor internalization, desensitization and phosphorylation. The mechanisms involved in heterotrimeric G-protein coupling to the receptor, activation of the downstream signaling pathway by G proteins and the Ang II signal transduction pathways leading to specific cellular responses are discussed. In addition, recent work on the identification and characterization of novel proteins associated with carboxy1-terminus of the AT1 receptor is presented. These novel proteins will advance our understanding of how the receptor is internalized and recycled as they provide molecular mechanisms for the activation and regulation of G-protein-coupled receptors.
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 （P〉0.05）, but the expression of type Ⅲ procoagen mRNA was significantly stronger in the patients with portal hypertension than in those without portal hypertension （P〈 0.01）. CONCLUSION： Type Ⅲ procollagen and collagen might be important extra-cellular matrix resulting in neointimal formation and vascular remodeling in the pathogenesis of portal hypertensive vasculopathy. The pathological changes in splenic arteries and veins exist in portal hypertension patients. There might be an interaction between portal hypertension, splanchnic hyperdynamic circulation and splanchnic vasculopathy.
文摘AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCI4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitro-L-arginine (L-NNA)group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1mL of saline, L-NNA (3.3 mg/kg-d) and INDO (5 mg/kg·d) respectively through gastric tubes for one week/then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α, a stable hydrolytic product of PGI2, was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGFla (pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats (1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11, 75.21±6.89) were significantly higher than those in SO rats (725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGFla and serum NO2/7NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto- concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.
