Reduction Of Portal Venous Pressure Research Articles

Splenic Artery Ligation: An Ontable Bail-Out Strategy for Small-for-Size Remnants after Major Hepatectomy: A Retrospective Study.

It has been reported that the prevention of acute portal overpressure in small-for-size liver grafts leads to better postoperative outcomes. Accordingly, we aimed to investigate the feasibility of the technique of splenic artery ligation in a case series of thirteen patients subjected to major liver resections with evidence of small-for-size syndrome and whether the maneuver results in the reduction of portal venous pressure and flow. The technique was successful in ten patients, with splenic artery ligation alleviating portal hypertension significantly. Three patients required the performance of a portocaval shunt for the attenuation of portal hypertension. Portal inflow modulation via splenic artery ligation is a technically simple technique that can prove useful in the context of major hepatectomies as well as in liver transplantations and the early evaluation and modification of portal venous pressure post hepatectomy can be used as a practical tool to guide the effect of the intervention.

The Effect of Transjugular Intrahepatic Portosystemic Shunt Plus Partial Splenic Embolization for the Treatment of Patients with Recurrent Variceal Bleeding

Transjugular intrahepatic portosystemic shunt (TIPS) and partial splenic embolization (PSE) were two interventional therapies effective for the management of variceal bleeding with cirrhosis. This study aimed to investigate the effect of TIPS plus PSE for the treatment of patients with cirrhosis and recurrent variceal bleeding. This is a single-center, nonrandomized and retrospective study that included 32 patients undergoing TIPS alone (the TIPS group) and 16 patients undergoing TIPS plus PSE (the TIPS+PSE group). The 5-year cumulative rates of variceal rebleeding (20.0% vs. 37.9%, p = 0.027) and shunt stenosis (35.1% vs. 55.9%, p = 0.036) in the TIPS+PSE group were significantly lower than in the TIPS group, whereas the 5-year cumulative rates of shunt blockage (12.5% vs. 25.8%, p = 0.388), and all-cause mortality (37.5% vs. 69.3%, p = 0.414) were not statistically different between the two groups. The 2-year cumulative rate of remaining free of hepatic encephalopathy was also similar between the two groups (75.0% vs. 81.3%, p = 0.704). Cox-regression analyses showed that group and reduction of portal venous pressure before and after TIPS creation were associated with both variceal rebleeding and shunt stenosis, whereas only reduction of portal venous pressure (hazard ratio 0.648, 95% confidence interval: 0.444-0.946, p = 0.025) was associated with shunt blockage. No severe adverse event was observed in the two groups. TIPS+PSE is superior to TIPS alone in control of variceal rebleeding and shunt stenosis. Further prospective studies are warranted to confirm our findings.

Stent dysfunction after transjugular intrahepatic portosystemic shunt: Causes and countermeasures

Objective To investigate the causes of dysfunction of COOK bare stent, Wallgraft covered stent, and Fluency covered stent after transjugular intrahepatic portosystemic shunt ( TIPS) and related countermeasures. Methods The clinical data of 54 patients who were found to have stent dysfunction and underwent TIPS correction in our hospital from January 2011 to July 2017 were collected. Balloon dilatation, coaxial stent implantation, or parallel TIPS was selected based on angiography results and portal venous pressure to repair stent dysfunction. The Kruskal-Wallis H test was used to compare in-stent restenosis or occlusion time between the three types of stents, and the paired t-test was used to compare portal vein perfusion ( PVP) before and after correction. Radiological examination was performed to evaluate stent dysfunction, and the cause of in-stent restenosis or occlusion was analyzed. Results TIPS correction was successfully performed for all 54 patients. Stenosis was observed in the hepatic vein, the liver parenchyma, or the portal vein, and there was a high incidence rate within 6-24 months after surgery. The median time to stenosis or occlusion was 17. 0 months for COOK bare stent, 10. 0 months for Wallgraft covered stent, and 17. 0 months for Fluency covered stent. COOK bare stent and Fluency covered stent had a longer time to stenosis or occlusion than Wallgraft covered stent ( P = 0. 013 and 0. 023) , and there was no significant difference in the time to stenosis or occlusion between COOK bare stent and Fluency covered stent ( P = 0. 893) . As for the surgical procedure of TIPS correction, 4 patients underwent balloon dilatation, 39 underwent coaxial stent implantation, and 11 underwent parallel TIPS. There was a significant reduction in portal venous pressure after surgery ( 25. 6 ± 4. 8 cm H2O vs 34. 7 ± 6. 4 cm H2O, P < 0. 001) . Conclusion Wallgraft stent has a significantly shorter time to stent dysfunction after TIPS than COOK bare stent and Fluency covered stent, suggesting that Wallgraft stent is not suitable for the initial establishment of TIPS shunt. Correction procedures should be selected based on actual conditions to repair stent dysfunction and restore shunt patency.

Patterns of splenic arterial enhancement on computed tomography are related to changes in portal venous pressure.

One of the striking features of splenic imaging is variable heterogeneous gyriform arterial enhancement on dynamic computed tomography (CT). We speculated that these patterns of arterial enhancement may reflect changes in splenic micro-circulation related to changes in portal venous pressure. To test this hypothesis, we evaluated arterial phase CT scans performed before and after liver transplantation (n=91), as this is the most effective way of alleviating portal hypertension. We developed novel grading systems to assess heterogeneity. Two control groups were used: patients with cirrhosis undergoing transarterial chemoembolization (TACE) (n=28) and patients with cirrhosis on the liver transplant waiting list who had repeated CT scans (n=28). Splenic arterial heterogeneity increased in 55% of transplant patients compared with 14% in the TACE patients and 4% in the waiting list patients (P<0.0001). Mean Hounsfield units in areas of splenic enhancement were 71.7±2 before transplant and 90.1±2.5 after transplant (P<0.01). In contrast, there were no significant changes following TACE (86.3±4.2 vs. 83.5±4.5; P=NS) or in waiting list patients (80.9±4.6 vs. 73.8±3.7; P=NS). We have shown the heterogeneous gyriform enhancement patterns significantly increase following liver transplantation but not after TACE or in waiting list patients. We suggest that these changes are due to the reduction in portal venous pressure and likely reflect changes in splenic micro-circulation. These changes may be important in the pathophysiology of hypersplenism.

Human Atrial Natriuretic Peptide in Cold Storage of Donation After Circulatory Death Rat Livers: An Old but New Agent for Protecting Vascular Endothelia?

Current critical shortage of donor organs has increased the use of donation after circulatory death (DCD) livers for transplantation, despite higher risk for primary nonfunction or ischemic cholangiopathy. Human atrial natriuretic peptide (hANP) is a cardiovascular hormone that possesses protective action to vascular endothelia. We aimed to clarify the therapeutic potential of hANP in cold storage of DCD livers. Male Wistar rats were exposed to 30-minute warm ischemia in situ. Livers were then retrieved and cold-preserved for 6 hours with or without hANP supplementation. Functional and morphological integrity of the livers was evaluated by oxygenated ex vivo reperfusion at 37°C. hANP supplementation resulted in significant reduction of portal venous pressure (12.2 ± 0.5 versus 22.5 ± 3.5 mm Hg, P < 0.001). As underlying mechanisms, hANP supplementation significantly increased tissue adenosine concentration (P = 0.008), resulting in significant upregulation of endothelial nitric oxide synthase and significant downregulation of endothelin-1 (P = 0.01 and P = 0.004 vs. the controls, respectively). Consequently, hANP significantly decreased transaminase release (P < 0.001) and increased bile production (96.2 ± 18.2 versus 36.2 ± 15.2 μL/g-liver/h, P < 0.001). Morphologically, hepatocytes and sinusoidal endothelia were both better maintained by hANP (P = 0.021). Electron microscopy also revealed that sinusoidal ultrastructures and microvilli formation in bile canaliculi were both better preserved by hANP supplementation. Silver staining also demonstrated that hANP significantly preserved reticulin fibers in Disse space (P = 0.017), representing significant protection of sinusoidal frameworks/architectures. Supplementation of hANP during cold storage significantly attenuated cold ischemia/warm reperfusion injury of DCD livers.

Elevated Liver Regeneration in Response to Pharmacological Reduction of Elevated Portal Venous Pressure by Terlipressin After Partial Hepatectomy

Liver regeneration is of crucial importance for patients undergoing living liver transplantations or extended liver resections and can be associated with elevated portal venous pressure, impaired hepatic regeneration, and postoperative morbidity. The aim of this study was to assess whether reduction of portal venous pressure by terlipressin improves postoperative liver regeneration in normal and steatotic livers after partial hepatectomy in a rodent model. Portal venous pressure was assessed after minor (30%), standard (60%), or extended (80%) partial hepatectomy (PH) in mice with and without liver steatosis. Liver regeneration was assessed by BrdU incorporation and Ki-67 immunostaining. Portal venous pressure was significantly elevated post-PH in mice with normal and steatotic livers compared to sham-operated mice. Reduction of elevated portal pressure after 80% PH by terlipressin was associated with an increase of hepatocellular proliferation. In steatotic livers, animals treated with terlipressin had an increase in liver regeneration after 30% PH and increased survival after 60% PH. Mechanistically, terlipressin alleviated IL-6 mRNA expression following PH and down-regulated p21 and GADD45 mRNA suggesting a reduction of cell cycle inhibition and cellular stress. Reduction of elevated portal pressure post-PH by the use of terlipressin improves liver regeneration after PH in lean and steatotic mouse livers.

Effects of tetramethylpyrazine on portal hypertensive rats.

The effects of tetramethylpyrazine, an alkaloid isolated from a Chinese herb Ligusticum wallichii Franch have been assessed in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Two weeks after ligation, when the hyperdynamic state had stabilized, rats were anaesthetized after an overnight fast and cannulated for measurement of mean arterial pressure, portal venous pressure, cardiac index and heart rate. Tetramethylpyrazine (3.0, 9.9 and 30mgkg(-1)) induced dose-dependent reductions of portal venous pressure and mean arterial pressure after intravenous infusion. The maximum percentage reduction of portal venous pressure after tetramethylpyrazine was 6.0+/-0.8, 9.3+/-1.6 and 20+/-2% of baseline for doses of 3.0, 9.9 and 30.0mgkg(-1), respectively. Also, total peripheral resistance was significantly reduced by tetramethylpyrazine and cardiac index was slightly increased. Our results showed that tetramethylpyrazine induced portal pressure reduction in portal hypertensive rats.

Portal hypotensive effects of tetrandrine and verapamil in portal hypertensive rats.

The portal hypotensive effects of tetrandrine and verapamil (both calcium-channel blockers) were assessed in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Both tetrandrine (4, 8, 16 and 24 mg kg-1) and verapamil (0.5, 1.0, 1.5 and 2.0 mg kg-1) induced dose-dependent decreases of portal venous pressure and mean arterial pressure after intravenous infusion. for example, infusion of tetrandrine (16 mg kg-1) induced a maximum reduction of portal venous pressure and mean arterial pressure approximately 1 min after the start of infusion. Portal venous pressure decreased from baseline (12.5 mmHg) to 10.0 mmHg, and mean arterial pressure from baseline (90 mmHg) to 80 mmHg. Heart rate decreased from 250 to 240 beats min-1. At 24 mg kg-1, tetrandrine reduced portal venous pressure and mean arterial pressure to 20.3 +/- 2.4% and 28.4 +/- 1.4% of baseline, respectively. Our results show that both tetrandrine and verapamil induce portal pressure reduction in portal hypertensive animals.

Understanding the splenic contribution to portal flow: The role of splenic artery ligation as inflow modification in living donor liver transplantation

Understanding the splenic contribution to portal flow: The role of splenic artery ligation as inflow modification in living donor liver transplantation

Experimental study on iNOS gene transfer mediated by liposome to treat portal hypertension in cirrhotic rats

To evaluate the effects of iNOS gene transfer on portal hypertensive rats. Eukaryotic expression plasmid pcDNA(3)/iNOS was used to transfect sinusoidal endothelial cells (SEC) mediated by Lipofectamine. Transfection rate and gene exspression were detected. Hepatic cirrhosis was induced in male Sprague-Dawley rats by intraperitoneal injection of carbon tetrachloride, and the cirrhotic rats were divided into three groups:Liposome-pcDNA(3)/iNOS (n = 10), Tris buffer (n = 10) and nude plasmid (n = 10), which were injected into the portal vein of experiment cirrhotic rats respectively. Five days later, animals were killed, immunohistochemistry and spectrophotometry methods were used to measure the expression of iNOS and the amount of NO production. Eukaryotic expression plasmid pcDNA(3)/iNOS could effectively transfect SEC and express corresponding gene products. Following iNOS gene transfer, compared with the two controlled groups, iNOS expression and the NO production were significantly increased meanwhile portal pressure was decreased significantly. The iNOS gene transfer is a feasible and an effective approach to treat portal hypertension in cirrhotic rats which could increase the expression of intra-hepatic iNOS and the amount of NO production thus leading to a remarkable reduction of portal venous pressure.

Beneficial effects of combined terlipressin and tetramethylpyrazine administration on portal hypertensive rats

The purpose of this study was to investigate the therapeutic effects of terlipressin (TP) alone or in combination with tetramethylpyrazine (TMP) on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL, without cirrhosis) or bile duct ligation (BDL, with cirrhosis) in Sprague-Dawley rats. Each PVL or BDL rat received only one of the two regimens: vehicle for 3 min followed by TP (0.017 mg x kg(-1) x min(-1) for 3 min) or TMP (10 mg x kg(-1) x min(-1) for 3 min) followed by TP. In PVL rats, infusion of vehicle followed by TP induced significant reduction of portal venous pressure (PVP, -15.0+/-1.0%) and prominent elevation of mean arterial pressure (MAP, 57.3+/-8.1%) as well as total peripheral resistance (TPR, 113+/-11%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -26.3+/-1.1%). Infusion of TMP followed by TP induced significant reduction of PVP (-20.3+/-0.4%) and CI (-9.9+/-1.2%) and significant elevation of MAP (31.3+/-2.5%) and TPR (46.0+/-4.1%) from baseline. In BDL rats, infusion of vehicle followed by TP also induced significant reduction of PVP (-13.8+/-1.7%) but an increase in MAP (57.1+/-2.2%) and TPR (101+/-6%) from baseline, and there also was a cardiodepressant response (CI, -21.4+/-2.3%). Infusion of TMP followed by TP induced significant reduction of PVP (-18.9+/-1.4%) and CI (-11.9+/-2.1%), but an increase in MAP (36.2+/-2.5%) and TPR (55.0+/-5.2%). Compared with vehicle followed by TP, TMP not only significantly enhanced portal hypotensive (PVP reduction) effects of TP but also attenuated the systemic pressor (MAP and TPR elevation) and cardiodepressant (CI reduction) effects of TP in both PVL and BDL rats. Our results suggest that TP, alone or in combination with TMP, induced portal hypotensive effects in two models of portal hypertensive rats. Combination of TP and TMP was beneficial in enhancing portal hypotensive effects of TP and ameliorating the systemic pressor and cardiodepressant effects of TP.

Portal hypotensive effects of combined terlipressin and DL-028, a synthetic alpha 1 adrenoceptor antagonist administration on anesthetized portal hypertensive rats.

The purpose of this study was to investigate the therapeutic effects of terlipressin, alone or in combination with DL-028, a synthetic alpha 1-adrenoceptor antagonist on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL) or bile duct ligation (BDL) in Sprague-Dawley rats. Each portal hypertensive rat received only one of the two regimens: vehicle plus terlipressin or DL-028 plus terlipressin. Terlipressin dosage was 0.017 mg/kg/min infused for 3 min, while vehicle or DL-028 (0.50 microgram/kg/min) was continuously infused for 40 min, starting 10 min before terlipressin infusion. In PVL rats, infusions of vehicle plus terlipressin induced significant, maximum reduction of portal venous pressure (PVP, -11.0 +/- 1.8%) and prominent elevation of mean arterial pressure (MAP, 50.3 +/- 9.0%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (-17.5 +/- 2.8%) and MAP elevation (39.8 +/- 7.4%). In BDL rats, infusion of vehicle plus terlipressin also induced significant, maximum reduction of PVP (-6.8 +/- 2.1%) and prominent elevation of MAP (61.4 +/- 7.8%) from baseline. Infusions of DL-028 plus terlipressin induced maximum PVP reduction (-17.9 +/- 2.2%) and MAP elevation (47.9 +/- 7.4%). Compared to vehicle plus terlipressin, DL-028 significantly enhanced portal hypotensive effects of and attenuated systemic pressor effects of terlipressin in both PVL and BDL rats. Our results suggest that terlipressin, alone or in combination with DL-028, induced portal hypotensive effects in portal hypertensive rats. The combination of terlipressin with DL-028 was beneficial in enhancing the portal hypotensive effects and ameliorating the systemic pressor effects of terlipressin.

Beneficial effects of combined terlipressin and tetramethylpyrazine administration on portal hypertensive rats

The purpose of this study was to investigate the therapeutic effects of terlipressin (TP) alone or in combination with tetramethylpyrazine (TMP) on anesthetized portal hypertensive rats. Portal hypertension was induced by either partial portal vein ligation (PVL, without cirrhosis) or bile duct ligation (BDL, with cirrhosis) in Sprague-Dawley rats. Each PVL or BDL rat received only one of the two regimens: vehicle for 3 min followed by TP (0.017 mg x kg(-1) x min(-1) for 3 min) or TMP (10 mg x kg(-1) x min(-1) for 3 min) followed by TP. In PVL rats, infusion of vehicle followed by TP induced significant reduction of portal venous pressure (PVP, -15.0+/-1.0%) and prominent elevation of mean arterial pressure (MAP, 57.3+/-8.1%) as well as total peripheral resistance (TPR, 113+/-11%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -26.3+/-1.1%). Infusion of TMP followed by TP induced significant reduction of PVP (-20.3+/-0.4%) and CI (-9.9+/-1.2%) and significant elevation of MAP (31.3+/-2.5%) and TPR (46.0+/-4.1%) from baseline. In BDL rats, infusion of vehicle followed by TP also induced significant reduction of PVP (-13.8+/-1.7%) but an increase in MAP (57.1+/-2.2%) and TPR (101+/-6%) from baseline, and there also was a cardiodepressant response (CI, -21.4+/-2.3%). Infusion of TMP followed by TP induced significant reduction of PVP (-18.9+/-1.4%) and CI (-11.9+/-2.1%), but an increase in MAP (36.2+/-2.5%) and TPR (55.0+/-5.2%). Compared with vehicle followed by TP, TMP not only significantly enhanced portal hypotensive (PVP reduction) effects of TP but also attenuated the systemic pressor (MAP and TPR elevation) and cardiodepressant (CI reduction) effects of TP in both PVL and BDL rats. Our results suggest that TP, alone or in combination with TMP, induced portal hypotensive effects in two models of portal hypertensive rats. Combination of TP and TMP was beneficial in enhancing portal hypotensive effects of TP and ameliorating the systemic pressor and cardiodepressant effects of TP.

Portal Hypotensive Effects of DL-028 and Prazosin on Portal Hypertensive Rats

The portal hypotensive effects of prazosin and DL-028 (chem- ical name: 3-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]- 2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one(27b)), a synthetic α₁-adrenoceptor antagonist, were assessed in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Two weeks after ligation, when the hyperdynamic state was stabilized the rats were anesthetized after an overnight fast and cannulated for measuring mean arterial pressure (MAP), portal venous pressure (PVP), cardiac index (CI) and heart rate (HR). Both DL-028 and prazosin (1, 3.3 and 10 µg/kg) induced dose-dependent decreases of PVP and MAP after intravenous infusion, with effects lasting for longer than 30 min. The maximum percentage reduction of PVP after DL-028 was 10, 10 and 15%, respectively, for the dosages given (1, 3.3 and 10 µg/kg), and 5, 12 and 25%, respectively, after prazosin. CI was not changed by either drug. HR was not changed by either drug except DL-028 at 10.0 µg/kg with a bradycardiac effect. Our results showed that both DL-028 and prazosin reduced PVP in portal hypertensive rats.

Hemodynamic effects of acute tetrandrine and terlipressin administration on portal hypertensive rats

The purpose of this study was to investigate the therapeutic effects of tetrandrine and terlipressin, alone or in combination, on anesthetized portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Each portal hypertensive rat received one of three regimens: vehicle plus terlipressin, tetrandrine (.50 mg.kg-1.min-1) [corrected] plus terlipressin, or tetrandrine (.75 mg.kg-1.min-1) [corrected] plus terlipressin. Terlipressin dosage was 0.025 mg.kg-1.min-1 [corrected] infused for 3 min. Infusion of vehicle followed by terlipressin induced significant reduction of portal venous pressure (PVP, -24.3 +/- 1.5%) and prominent elevation of mean arterial pressure (MAP, 73.3 +/- 4.6%) as well as total peripheral resistance (TPR, 133 +/- 8%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -30.6 +/- 3.8%; heart rate, HR, -10.4 +/- 2.1%). Infusion of tetrandrine (.50 mg.kg-1.min-1) [corrected] induced significant reduction of PVP (-7.2 +/- 0.9%), MAP (-12.5 +/- 1.6%), and TPR (-14.3 +/- 4.2%) from baseline. Infusions of tetrandrine followed by terlipressin induced significant reduction of PVP (-14.2 +/- 2.4%) but an increase in MAP (22.6 +/- 2.7%) and TPR (71.1 +/- 10.5%). Infusion of tetrandrine (.75 mg.kg-1.min-1) [corrected] induced significant reduction of PVP (-9.9 +/- 0.8%). MAP (-19.2 +/- 2.1%), and TPR (-24.1 +/- 2.1%) from baseline. Infusions of tetrandrine followed by terlipressin induced significant reduction of PVP (-14.0 +/- 1.1%) but an increase in MAP (14.0 +/- 2.7%) and TPR (75.2 +/- 5.2%). Compared with vehicle followed by terlipressin, tetrandrine significantly attenuated systemic pressor (MAP and TPR elevation), cardiodepressant (CI reduction) as well as portal hypotensive (PVP reduction) effects of terlipressin. Our results suggest that tetrandrine and terlipressin, alone or in combination, induced portal hypotensive effects in portal hypertensive rats. Combined tetrandrine and terlipressin administration ameliorated systemic pressor and cardiodepressant effects of terlipressin, but it also attenuated the latter's portal hypotensive effects.

The treatment of oesophageal varices: a debate and a discussion.

At the Biennial Meeting of the International Association for the Study of the Liver, in Cape Town, South Africa, 20-24 February 1996, the treatment of oesophageal varices was selected as a subject for the discussion of controversies in portal hypertension. This review gives a summary of that discussion. Dr Didier LeBrec gave a broad overview of the medical management of oesophageal varices by presenting a list of 52 pharmacological agents that reduce portal venous pressure and presented the advantages and disadvantages of each. He emphasized that recent randomized clinical trials (RCT) have demonstrated that propranolol delays and decreases the occurrence of haemorrhage from varices in patients who have not previously suffered such complications. He also reported that isosorbidemononitrate is equally effective and further enhances the effect of propranolol. He also reported that the effects of propranolol plus endoscopic sclerotherapy (EST) were more effective than EST alone in preventing haemorrhage, but not in improving survival. Finally he noted that propranolol in high dosage did not prevent the development of large varices in cirrhotic patients with small or undetectable varices. Dr John Terblanche compared the efficacy of EST and endoscopic ligation of varices (ELV) and reported that all four RCTs found ELV to be superior. He discussed portacaval anastomosis (PCA) and concluded that only emergency PCA as reported by Orloff, is thought to be truly beneficial, and suggested that EST, plus ELV may be the treatment of choice. Dr Harold O. Conn, who served as the moderator of this session summarized the presentations and pointed out that liver transplantation is the most effective form of therapy of all, albeit extremely complex and expensive. He discussed transjugular intrahepatic portosystemic shunts (TIPS), the newest form of therapy, and emphasized its virtues (immediate reduction of portal venous pressure) and its limitations (frequent portosystemic encephalopathy and frequent spontaneous stenoses). He presented a brief discussion of the prevention of the development of the varices themselves, currently termed "pre-primary prophylaxis', a hope for the future. He ended with "Predictions' which if proven correct will give a preview of portal hypertension in the 21st century.

Hemodynamic effects of acute tetrandrine and terlipressin administration on portal hypertensive rats

The purpose of this study was to investigate the therapeutic effects of tetrandrine and terlipressin, alone or in combination, on anesthetized portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague-Dawley rats. Each portal hypertensive rat received one of three regimens: vehicle plus terlipressin, tetrandrine (.50 mg.kg-1.min-1) [corrected] plus terlipressin, or tetrandrine (.75 mg.kg-1.min-1) [corrected] plus terlipressin. Terlipressin dosage was 0.025 mg.kg-1.min-1 [corrected] infused for 3 min. Infusion of vehicle followed by terlipressin induced significant reduction of portal venous pressure (PVP, -24.3 +/- 1.5%) and prominent elevation of mean arterial pressure (MAP, 73.3 +/- 4.6%) as well as total peripheral resistance (TPR, 133 +/- 8%) from baseline, and there was a cardiodepressant response (cardiac index, CI, -30.6 +/- 3.8%; heart rate, HR, -10.4 +/- 2.1%). Infusion of tetrandrine (.50 mg.kg-1.min-1) [corrected] induced significant reduction of PVP (-7.2 +/- 0.9%), MAP (-12.5 +/- 1.6%), and TPR (-14.3 +/- 4.2%) from baseline. Infusions of tetrandrine followed by terlipressin induced significant reduction of PVP (-14.2 +/- 2.4%) but an increase in MAP (22.6 +/- 2.7%) and TPR (71.1 +/- 10.5%). Infusion of tetrandrine (.75 mg.kg-1.min-1) [corrected] induced significant reduction of PVP (-9.9 +/- 0.8%). MAP (-19.2 +/- 2.1%), and TPR (-24.1 +/- 2.1%) from baseline. Infusions of tetrandrine followed by terlipressin induced significant reduction of PVP (-14.0 +/- 1.1%) but an increase in MAP (14.0 +/- 2.7%) and TPR (75.2 +/- 5.2%). Compared with vehicle followed by terlipressin, tetrandrine significantly attenuated systemic pressor (MAP and TPR elevation), cardiodepressant (CI reduction) as well as portal hypotensive (PVP reduction) effects of terlipressin. Our results suggest that tetrandrine and terlipressin, alone or in combination, induced portal hypotensive effects in portal hypertensive rats. Combined tetrandrine and terlipressin administration ameliorated systemic pressor and cardiodepressant effects of terlipressin, but it also attenuated the latter's portal hypotensive effects.

Influence of nitroglycerin on portal pressure and gastric mucosal hemodynamics in patients with cirrhosis.

We studied 30 patients with cirrhosis to determine the effect of nitroglycerin on portal and gastric mucosal hemodynamics. Systemic hemodynamics, portal venous pressure (PVP), the hemoglobin index (IHB), and the oxygen saturation index (ISO2) of the gastric mucosa were measured before and after a continuous infusion of nitroglycerin. The patients were divided into two groups according to the presence or absence of major portal-systemic collateral routes on portograms. Nitroglycerin caused a reduction in PVP in all patients. Although there was no significant difference in systemic hemodynamic changes between the two groups, the reduction in PVP in patients with major portal-systemic collaterals was significantly higher than in those without major collaterals. A nitroglycerin infusion, at a dose of 1.0 micrograms/kg per min for 10 min, produced a reduction in both IHB (-16%, P < 0.001) and ISO2 (-13%, P < 0.001) in the gastric mucosa, indicating gastric mucosal ischemia secondary to splanchnic vasoconstriction. These findings suggest that the continuous infusion of nitroglycerin reduces PVP in cirrhotic patients, particularly in those with major portal-systemic collaterals, and reduces the congestion of the gastric mucosa in patients with portal hypertension.

Increased Sympathetic Nervous Activity and the Effects of Its Inhibition with Clonidine in Alcoholic Cirrhosis

To study disturbances in sympathetic nervous system function in patients with alcoholic cirrhosis and the effect of clonidine on such disturbances. Cross-sectional physiologic and neurochemical evaluation of patients with cirrhosis and of healthy controls; an uncontrolled trial of intravenous clonidine in the cirrhotic patients. Forty-four hospitalized patients with biopsy-proven alcoholic cirrhosis and 31 healthy controls. Intravenous clonidine. Radiotracer-derived measures of norepinephrine release to plasma, central hemodynamics, wedge hepatic vein pressure, and measures of renal function. In patients with cirrhosis, clonidine reduced previously elevated norepinephrine overflow rates for the whole body, kidneys, and hepatomesenteric circulation. This sympathetic inhibition was accompanied by the following potentially clinically beneficial effects: the lowering of renal vascular resistance (median reduction, 24%; 95% CI, 14% to 31%), the elevation of glomerular filtration rate (median increase, 27%; CI, 14% to 39%), and the reduction of portal venous pressure (median reduction, 25%; CI, 18% to 32%). The norepinephrine and hemodynamic responses to graded clonidine dosing (1, 2, and 3 micrograms/kg body weight intravenously) indicated that the sympathetic outflow to the hepatomesenteric circulation was more sensitive to pharmacologic suppression with clonidine than was the sympathetic outflow to the systemic circulation. The sympathetic nerves to the kidneys, heart, and hepatomesenteric circulation are stimulated in patients with cirrhosis. Clonidine inhibits these activated sympathetic outflows differentially, which could possibly provide a basis for the selective pharmacologic treatment of portal hypertension in patients with cirrhosis.

The effects of the combination of phentolamine and vasopressin on hepatic and systemic hemodynamics in girrhotic portal hypertensive dog model

The experimental study was aimed at elucidating the effects of phentolamine and vasopressin used separately or in combination on hepatic and systemic hemodynamics in cirrhotic portal hypertensive dogs. The results showed that either of the two drugs used separately could lead to reduction in portal venous pressure and could also influence systemic hemodynamics or lower hepatic blood flow. When phentolamine in combination with vasopressin was administered, no side-effect could be found on hepatic and systemic hemodynamics, suggesting that the drugs used in combination could efficaciously decrease portal hypertension and counteract their respective side-effect. This combination therapy will be useful in treating bleeding from esophageal variceal rupture in cirrhotic patients with portal hypertension.