Comparison of isolated hepatocytes and tissue slices for study of liver hypothermic preservation/reperfusion injury

BACKGROUND/AIMS: Effective protection from the risk of variceal bleeding is achieved when the hepatic venous pressure gradient is reduced to 12 mmHg or at least by 20% of baseline values. Such a marked decrease is rarely achieved with propranolol, and new agents or combinations of them are now being explored. The present randomized study investigated whether chronic treatment with the combination of propranolol plus molsidomine, a preferential venous dialator that reduces hepatic venous pressure gradient and does not cause pharmacological tolerance, achieves greater reduction in hepatic venous pressure gradient than propranolol alone. METHODS: A hemodynamic study was performed in 34 patients with cirrhosis with portal hypertension in baseline conditions and after 3 months of chronic oral treatment with propranolol alone (n = 19) or propranolol plus molsidomine (n = 15). RESULTS: Propranolol produced a significant reduction in hepatic venous pressure gradient (-16%, p < 0.01). Propranolol plus molsidomine also caused a slight but significant decrease in hepatic venous pressure gradient (-9%, p < 0.05). Hepatic blood flow and the hepatic and intrinsic clearance of indocyanine green were significantly reduced by propranolol. The combined administration of propranolol+molsidomine significantly reduced hepatic blood flow but not hepatic and intrinsic clearance of indocyanine green. Both treatment groups produced similar reduction in azygos blood flow, heart rate and cardiac output. However, contrary to propranolol alone, propranolol plus molsidomine did not increase cardiopulmonary pressures. CONCLUSIONS: The current study shows that although the combined administration of propranolol plus molsidomine prevents some of the adverse effects of propranolol on liver function and cardiopulmonary pressures, it does not achieve a greater reduction in hepatic venous pressure gradient than propranolol alone and therefore, does not support the use of this combined therapy for the pharmacological treatment of portal hypertension.     

Effect of spinal cord injury on the permeability of the blood-brain and blood-spinal cord barriers to the neurotropin PACAP

BACKGROUND & AIMS: The association of prazosin to propranolol enhances the decrease in portal pressure but may cause hypotension and sodium retention. The aim of this study was to compare the portal pressure reduction and safety of the combination of propranolol plus prazosin with that of propranolol plus isosorbide-5-mononitrate (ISMN). METHODS: Fifty-six portal-hypertensive cirrhotics received randomly propranolol plus prazosin (n = 28) or propranolol plus ISMN (n = 28) orally for 3 months. Hemodynamics and liver and renal function were assessed at baseline and after 3 months. RESULTS: Propranolol plus prazosin caused a greater reduction in hepatic venous pressure gradient (HVPG) than propranolol plus ISMN (-24.2% +/- 11% vs. -16.1% +/- 11%; P < 0.01). A reduction in HVPG of > 20% was significantly more frequent in the propranolol plus prazosin group than in the propranolol plus ISMN group (85% vs. 53%; P < 0.05). Neither treatment modified hepatic blood flow, quantitative liver function test results, glomerular filtration rate, plasma renin activity, or plasma aldosterone level. Side effects occurred in 13 patients receiving propranolol plus prazosin compared with 7 receiving propranolol plus ISMN (P = 0.16). CONCLUSIONS: Propranolol plus prazosin has a greater portal pressure-lowering effect than propranolol plus ISMN. Both therapies were safe for liver and renal function. However, the combination of propranolol plus prazosin caused a greater decrease in arterial pressure and was less well tolerated than propranolol plus ISMN.     

Cytochrome P-450 inhibition blocks bone resorption in vitro and in vivo

BACKGROUND AND METHODS: To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS: In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION: The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.     

Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2

To determine the relationship between quantitative Doppler parameters of portal, hepatic, and splanchnic circulation and hepatic venous pressure gradient (HVPG), variceal size, and Child-Pugh class in patients with alcoholic cirrhosis, we studied forty patients with proved alcoholic cirrhosis who underwent Doppler ultrasonography, hepatic vein catheterization, and esophagoscopy. The following Doppler parameters were recorded: time-averaged mean blood velocity, volume flow of the main portal vein flow, and resistance index (RI) of the hepatic and of the superior mesenteric artery. Doppler findings were compared with HVPG, presence and size of esophageal varices, and Child-Pugh class. There was a significant inverse correlation between portal velocity and HVPG (r = -.69), as well as between portal vein flow and HVPG (r = -.58). No correlation was found between RI in the hepatic artery or superior mesenteric artery and HVPG. No correlation was found between portal vein measurements and presence and size of varices. Severe liver failure was associated with lower portal velocity and flow. In patients with alcoholic cirrhosis, only portal vein blood velocity and flow, but neither hepatic nor mesenteric artery RI, are correlated to the severity of portal hypertension and to the severity of liver failure.     

Endoscopic assessment of variceal volume and wall tension in cirrhotic patients: effects of pharmacological therapy

BACKGROUND & AIMS: Variceal rupture is believed to occur when variceal wall tension is excessive. The combined use of endosonography, allowing the objective measurement of variceal radius, and endoscopic measurement of transmural variceal pressure may enable assessment of this important parameter. The aim of this study was to assess the effects on variceal hemodynamics of drugs acting through different mechanisms: decreasing portocollateral blood flow (propranolol) or resistance (isosorbide-5-mononitrate [ISMN]). METHODS: Repeated measurements of variceal radius, volume (by endosonography), and transmural pressure (using endoscopic gauge) were performed in 27 cirrhotic patients at baseline and 40 minutes after double-blind administration of placebo (n = 9), propranolol (n = 9), or ISMN (n = 9). RESULTS: Placebo had no effect. Propranolol significantly reduced variceal volume (-32% +/- 26%; P = 0.01), radius (-12% +/- 9%; P < 0.005), and pressure (-26% +/- 10%; P < 0.0001). The resulting decrease in wall tension (-34% +/- 13%; P < 0.0005) exceeded that in transmural pressure (P < 0.01). ISMN reduced transmural variceal pressure (-26% +/- 21%; P < 0.005), but not radius (-3% +/-14%; NS) and volume (-9% +/- 31%; NS). CONCLUSIONS: The combination of endosonography and endoscopic measurement of transmural variceal pressure allows quantitative estimation of variceal wall tension. Propranolol and ISMN reduce similarly transmural variceal pressure. Propranolol, but not ISMN, reduces variceal volume and radius. Therefore, despite similar decreases in variceal wall tension, propranolol may offer a greater therapeutic effect than ISMN in portal hypertension.     

Differential effects on portal and effective hepatic blood flow. A comparison between transjugular intrahepatic portasystemic shunt and small-diameter H-graft portacaval shunt

OBJECTIVE: This study was undertaken to determine the effects of transjugular intrahepatic portasystemic shunt (TIPS) and small-diameter prosthetic H-graft portacaval shunt (HGPCS) on portal and effective hepatic blood flow. SUMMARY BACKGROUND DATA: Mortality after TIPS is higher than after HGPCS for bleeding varices. This higher mortality is because of hepatic failure, possibly a result of excessive diminution of hepatic blood flow. METHODS: Forty patients randomized prospectively to undergo TIPS or HGPCS had effective hepatic blood flow determined 1 day preshunt and 5 days postshunt using low-dose galactose clearance. Portal blood flow was determined using color-flow Doppler ultrasound. RESULTS: Treatment groups were similar in age, gender, and Child's class. Each procedure significantly reduced portal pressures and portasystemic pressure gradients. Portal flow after TIPS increased (21 mL/second +/- 11.9 to 31 mL/second +/- 16.9, p < 0.05), whereas it remained unchanged after HGPCS (26 mL/second +/- 27.7 to 14 mL/second +/- 41.1, p = n.s.). Effective hepatic blood flow was diminished significantly after TIPS (1684 mL/minute +/- 2161 to 676 mL/minute +/- 451, p < 0.05) and was unaffected by HGPCS (1901 mL/ minute +/- 1818 to 1662 mL/minute +/- 1035, p = n.s.). CONCLUSIONS: Both TIPS and HGPCS achieved significant reductions in portal vein pressure gradients. Portal flow increased after TIPS, although most portal flow was diverted through the shunt. Effective hepatic flow is reduced significantly after TIPS but well preserved after HGPCS. Hepatic decompensation and mortality after TIPS may be because, at least in part, of reductions in nutrient hepatic flow.     

Differences in binding to the solid substratum and extracellular matrix may explain isoform-specific paracrine effects of platelet-derived growth factor

Fourteen normal subjects (18-42 y) were studied using venous occlusion plethysmography to investigate the characteristics and reproducibility of the forearm vasoconstrictor response following a prolonged venous occlusion stimulus. Upon release of the stimulus, a transient vasodilation is followed by a vasoconstriction. As the stimulus of venous occlusion pressure increased (40, 60, 80, and 100 mmHg for 5 min), there was a significant increase in maximum flow (p = 0.01). Minimum relative flow (minimum divided by control) was unchanged except at the highest occlusion pressure (0.49 +/- 0.05, 0.38 +/- 0.04, 0.47 +/- 0.07, 0.66 +/- 0.12, p = 0.04). As venous occlusion duration increased (3, 4, 5, and 6 min at 80 mmHg), there was no significant change in minimum relative flow (p = 0.73). With increasing ambient temperature (18, 23, and 28 degrees C), there were no significant changes in maximum or minimum relative flows (p = 0.40 and 0.25, respectively). Minimum relative flow was not significantly altered following occlusion with a 2.5-cm cuff vs. a 10-cm cuff (p = 0.77). Thus, the vasoconstriction response was reproducible over a range of venous occlusion stimuli and experimental conditions. We conclude that dynamic vascular responsiveness to prolonged venous occlusion can be measured by venous plethysmography and that calculation of the minimum flow relative to control flow is an appropriate and reproducible index of the vasoconstrictor response. Based on our studies and to conveniently measure these changes, we recommend a 10-cm venous occlusion cuff, with a pressure < or = 80 mmHg, for durations < or = 5 min, in an ambient temperature of 23 degrees C.     

Some genetic aspects of ovarian tumors

BACKGROUND: Propranolol and isosorbide-5-mononitrate (ISMN) are increasingly used in the prophylaxis of variceal haemorrhage in cirrhosis. However, recent studies have suggested that these drugs may compromise renal function, possibly by reducing renal blood flow. AIMS: To assess the acute effects of propranolol and ISMN on renal blood flow and other haemodynamic parameters in cirrhosis. PATIENTS AND METHODS: Twenty six cirrhotic patients were given either 80 mg propranolol, 20 mg ISMN, or a combination of the two drugs. Unilateral renal blood flow (RBF), azygos blood flow (AZBF), hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and heart rate (HR) were recorded prior to and one hour after drug administration. RESULTS: Propranolol caused a reduction in HR (p < 0.005), AZBF (p < 0.01), and HVPG (p = 0.05), but no change in MAP or RBF (454.1 (77.3) versus 413.9 (60.3) ml/min). ISMN reduced MAP (p < 0.005) and HVPG (p < 0.01), but had no effect on HR, AZBF, or RBF (302.5 (49.4) versus 301.7 (58.8) ml/min). Combined treatment reduced MAP (p < 0.005), AZBF (p < 0.05), and HVPG (p = 0.002), but HR and RBF (419.2 (62.6) versus 415.1 (61.1) ml/min) remained unchanged. CONCLUSIONS: Despite the anticipated changes in other haemodynamic parameters, acute propranolol and/or ISMN administration did not reduce RBF. These drugs do not seem to compromise RBF in cirrhosis.     

Role of pseudolynchia canariensis in the transmission of haemoproteus turtur from the migrant Streptopelia turtur to new bird hosts in Egypt

OBJECTIVE: The aims of the study were to establish the roles of angiotensin II and of the cardiopulmonary baroreceptor reflex in the regulation of peripheral vascular tone in patients with cirrhosis. METHODS: Forearm blood flow responses to subsystemic, locally active intrabrachial infusions were measured in patients with Child's Grade C cirrhosis and matched controls using bilateral venous occlusion plethysmography. Responses were determined to the angiotensin II type I receptor antagonist, losartan, noradrenaline, angiotensin II and the nitric oxide synthase inhibitor, L-NG-monomethyl arginine. RESULTS: Losartan at 30 and 90 micrograms/min caused no significant change in blood flow in controls, but caused 23 +/- 6% and 27 +/- 5% increases in patients respectively (p < 0.001). Lower body negative pressure caused a mean bilateral reduction in forearm blood flow of 20 +/- 4% in controls (p < 0.001) but only tended to reduce flow (9 +/- 5%; p = 0.06) in patients (p < 0.001; controls vs. patients). Noradrenaline, angiotensin II and L-NG-monomethyl arginine caused significant vasoconstriction (p < 0.001) in both patients and controls although angiotensin II caused significantly less vasoconstriction in patients (p = 0.01). CONCLUSIONS: We conclude that angiotensin II makes an important contribution to basal peripheral vascular tone in patients with cirrhosis in the face of reduced vascular responses to its local administration. In addition, the vasoconstrictor response to cardiopulmonary baroreceptor unloading is attenuated despite normal vascular responses to noradrenaline. These responses are consistent with chronic activation of the renin-angiotensin and sympathetic nervous systems in patients with advanced cirrhosis.     

Fusion variations of pancreatic ducts in patients with anomalous arrangement of pancreaticobiliary ductal system

Portal vein flow was recorded by color Doppler sonography in 31 patients with chronic heart failure and 18 control subjects. Compared with patients showing a forward flow (Group A), those with reversed portal vein flow (Group B) had higher prevalence of tricuspid regurgitation (75% vs. 43%), hepatic congestion (100% vs. 30%) and ascites (50% vs. 18%), and showed higher right atrial pressure (25.3 +/- 3.01 mmHg vs. 11.8 +/- 5.75 mmHg, p < 0.01). In controls, portal vein pulsatility ratio was 0.66 +/- 0.08, in Group A it was 0.46 +/- 0.28 (p < 0.01), in Group B -0.60 +/- 0.19 (p < 0.01). Portal vein pulsatility ratio negatively correlated with right atrial pressure (r = -0.87; p < 0.01). In Group A, hepatic congestion, ascites and tricuspid regurgitation were associated with a higher portal vein pulsatility. This study indicates that portal vein pulsatility ratio reflects the level of impairment of the right heart.     

Modulation of intravariceal pressure with pentoxifylline: a possible new approach in the treatment of portal hypertension

OBJECTIVE: In this study the effect of the hemorheological agent pentoxifylline on the pressure of esophageal varices was investigated in portal hypertensive cirrhotic patients. METHODS: Intravariceal pressure was measured endoscopically using the direct puncture technique in 20 patients. Measurements were obtained under baseline conditions and 30 min after double-blind administration of pentoxifylline (1.4 mg/kg BW, n = 10 patients) or an identical volume of NaCl 0.9% solution (n = 10 patients). RESULTS: Under baseline conditions, intravariceal pressure was similar in pentoxifylline and placebo groups (17.3+/-5.5 mm Hg vs 18.8+/-4.6 mm Hg, respectively; p = N.S.). Placebo administration had no significant effect on intravariceal pressure (18.8+/-4.6 mm Hg vs 18.3+/-4.1 mm Hg; p = N.S.). In contrast, pentoxifylline caused a highly significant reduction of intravariceal pressure, (from 17.3+/-5.5 mm Hg to 11.4+/-5.9 mm Hg; p = 0.0001), the overall mean reduction being 36.1+/-14.1% mm Hg. CONCLUSIONS: We concluded that pentoxifylline, by reducing blood flow viscosity, caused a significant decrease in variceal pressure in patients suffering from portal hypertension.     

Doppler sonographic assessment of functional response of the right and left portal venous branches to a meal

PURPOSE: The aim of our study was to quantitate by Doppler sonography the blood flow in the right and left portal vein branches before and after a standard meal. We also assessed the functional response of the right and left lobes of the liver. METHODS: Portal blood flow was measured by Doppler sonography in the left and right portal vein branches and main portal trunk in 20 healthy volunteers in both fasting and postprandial states. The ratio between portal blood flow and liver volume (determined by MRI) was the portal flow index (PFI). RESULTS: Before the meal, a statistically significant difference in portal blood flow volume was observed between the right and left portal branches (p < 0.01). The right PFI (0.83 ml/minute/cm3) and left PFI (1.1 ml/minute/cm3) were also significantly different (p < 0.01). The increase in portal venous blood flow after a meal was found to be greater in the left portal branch (128%) than in the right portal branch (78%). The postprandial PFI also differed significantly (right, 1.54 ml/minute/cm3; left, 2.5 ml/minute/cm3). CONCLUSIONS: These findings suggest that the left lobe of the liver has a better postprandial compliance than the right lobe has.     

Propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: long-term hemodynamic and renal effects

The effect on kidney function, vasoactive systems and ascites outcome of long-term treatment with propranolol plus isosorbide-5-mononitrate, a combined therapy proven more effective than propranolol alone in decreasing portal pressure in the cirrhotic patient, is unknown. Thirty cirrhotic patients who survived acute variceal bleeding and were treated with propranolol plus isosorbide-5-mononitrate were studied. Portal and systemic hemodynamics (n = 15), inulin clearance, free water clearance, plasma renin activity, aldosterone concentration and prostaglandin E2 excretion (n = 20) were measured before and after 3 mo of treatment. In addition, data on ascites outcome in the entire series after a mean follow-up of 9.6 mo were compared with those of 30 patients undergoing elective sclerotherapy and with those of 30 patients treated with propranolol alone matched for age, sex, presence of ascites, Child-Pugh class and mean follow-up length included in other randomized controlled trials. Combined therapy significantly decreased the hepatic venous pressure gradient and azygos blood flow. In addition, no changes in inulin clearance, free water clearance, plasma renin activity, aldosterone concentration and prostaglandin E2 excretion occurred, despite a mild decrease in mean arterial pressure. Moreover, no differences among the three groups of patients studied in ascites outcome were found. These results suggest that long-term treatment with propranolol plus isosorbide-5-mononitrate does not impair kidney function, vasoactive systems or ascites outcome in cirrhotic patients.     

Massive lymphocytic infiltration of uterine leiomyomas associated with GnRH agonist treatment

OBJECTIVE: This study was designed to clarify how thrombopoietin (TPO) functions in and, to some extent, causes thrombocytopenia complicating liver cirrhosis and portal hypertension. METHODS: Our study population consisted of 19 cirrhotic and six noncirrhotic patients who underwent percutaneous transhepatic portography (PTP) and hepatic venography. RESULTS: The platelet counts of the cirrhotic patients were significantly lower than those of the noncirrhotic patients (8.7 +/- 4.1 vs 17.4 +/- 7 x 10(4)/microl; p < 0.01). The flow direction in the splenic vein was confirmed by PTP. Ten hepatofugal and nine hepatopetal flow directions in the splenic vein were noted among the cirrhotics. The hepatofugal group showed lower portal venous pressure (20 +/- 10 vs 32 +/- 4 cm H2O; p < 0.01) than the hepatopetal group and had a higher incidence of hepatic encephalopathy (six of 10 vs zero of nine; p < 0.01). The hepatic vein-portal difference in TPO did not differ substantially between the cirrhotics and noncirrhotics (0.12 +/- 0.04 vs 0.24 +/- 0.07 fmol/ml). Comparisons of this value among the three groups showed the TPO difference to be lowest in the hepatofugal group (hepatofugal: 0.04 +/- 0.03, hepatopetal: 0.21 +/- 0.07, noncirrhotic: 0.24 +/- 0.07; p < 0.05). CONCLUSIONS: Our findings suggest that TPO production in the cirrhotic liver is regulated by the portal blood supply to the liver. Thus, portal hemodynamics may play a critical role in the development of thrombocytopenia.     

Effects of canrenoate potassium, an aldosterone antagonist on portal hemodynamics in patients with compensated liver cirrhosis

BACKGROUND/AIMS: Long-term administration of spironolactone is reported to reduce portal pressure in cirrhotic patients. We examined the effects of acute administration of canrenoate potassium, an aldosterone antagonist, on portal hemodynamics in compensated cirrhotic patients using noninvasive duplex Doppler ultrasonography. MATERIALS AND METHODS: Baseline values were obtained in the fasting state, and then 200mg of canrenoate potassium in 10ml of saline solution was intravenously administered to 22 patients, whereas 10ml of saline solution was administered as a placebo to 8 patients. RESULTS: The portal cross-sectional area, portal blood velocity and portal blood flow decreased by 5.3 +/- 9.2, 10.4 +/- 8.7% and 13.0 +/- 12.4%, respectively at the nadir 60min after administration and these decreases persisted until 120min. Placebo did not affect these parameters of portal hemodynamics. Eleven responders, who had a more than 10% drop in portal blood flow 60min after administration, had significantly higher levels of plasma aldosterone than 8 non responders who had less than 10% drop. The reduction rate of portal blood flow was closely correlated with plasma aldosterone level. CONCLUSIONS: These findings suggest that aldosterone antagonist directly causes a reduction in portal blood flow, probably through inhibition of aldosterone-induced vasoconstrictive action.     

Contrast sensitivity in diabetic pregnancy

BACKGROUND: Adenosine is a potent mediator of arteriolar tone in particular during ischemia, hypoxia, and exercise. Functional disturbance of this dilatory pathway may be highly significant for the pathophysiology and pathogenesis of arterial hypertension. PATIENTS AND METHODS: Forearm blood flow (FBF) was quantified by venous occlusion plethysmography following intra-arterial infusion of adenosine at increasing doses in 13 patients with arterial hypertension (HT) and 12 age-matched normotensive controls (NT). Hyperemic peak flow was measured following 3 minutes of non-flow ischemia. RESULTS: FBF at rest was comparable in both groups and was dose-dependently increased by adenosine in both groups. In patients with HT adenosine-induced vasodilation was significantly impaired over the entire dose-response curve compared with NT (6.0 mumol/min: 14.5 +/- 1.0 versus 8.6 +/- 0.9 ml.min-1.100 ml-1 of tissue, p < 0.01). Maximum forearm blood flow during reactive hyperemia was also profoundly impaired in the hypertensive patients (-38%, p < 0.01). In the overall group of normotensive and hypertensive subjects, flow responses to adenosine were i) significantly correlated with peak flow (adenosine 2.0 mumol/min: r = 0.79, p < 0.001), and total flow during reactive hyperemia and ii) inversely related to the magnitude of arterial blood pressure. CONCLUSIONS: The study reported presents first evidence that adenosine-dependent dilation of forearm resistance arteries is impaired in patients with arterial hypertension. This vascular dysfunction is associated with the impairment of ischemia-induced reactive hyperemia which in turn may contribute to progressive end-organ damage in arterial hypertension.     

Effect of stimulation of hepatic nerves on hepatic O2 uptake and blood flow

Raising the hepatic venous pressure experimentally duplicates the type of hepatic congestion seen in many clinical situations including congestive heart failure. Venous pressure was controlled using a hepatic venous long circuit preparation and was raised by 6 cm blood (4.7 mm Hg) or 10 cm (7.8 mm Hg). Total splanchnic blood flow and oxygen uptake were reduced by these maneuvers but hepatic arterial flow was not altered nor was hepatic oxygen uptake. Blood flow in the portal vein decreased to 65 +/- 12% of control and gut oxygen uptake decreased to 60 +/- 14% of control. The data confirm that raised hepatic venous pressure does not produce hepatic edema in spite of massive prolonged fluid filtration across the liver into the peritoneum. In spite of a reduced (to 84 +/- 3% of control) hepatic oxygen delivery, the liver can maintain oxygen uptake (99 +/- 7% of control) by increasing oxygen extraction to appropriate levels. The hepatic artery in these cats were capable of myogenic vasoconstriction in response to altered arterial pressure, but in response to raised venous pressure no tendency for constriction was seen. This is in marked contrast to the vasoconstriction seen in isolated perfused livers where portal blood flow is held constant during the raised venous pressure.     

The postprandial portal flow is related to the severity of portal hypertension and liver cirrhosis

BACKGROUND/AIMS: Diminished postprandial portal hyperemia has been demonstrated by echo-Doppler flowmetry in patients with liver cirrhosis, but its diagnostic role is unclear. This prospective study was therefore undertaken in patients with varying severity of portal hypertension and degree of liver cirrhosis. METHODS: Portal flowmetry was performed in 66 patients with cirrhosis and 20 healthy volunteers during fasting and 30 min after ingestion of a standardized meal. Hemodynamic parameters were related to the degree of esophageal varices, variceal bleeding, portal hypertensive gastropathy and Child-Pugh score. RESULTS: The postprandial portal blood velocity increment was low in patients with esophageal varices of any degree (22-24%), compared to patients without varices (49%, p<0.01) and healthy controls (65%, p<0.001), but was not different in patients with or without variceal bleeding (22% vs. 20%). In contrast, the congestion index (CI; ratio of portal vein cross-sectional area and portal blood velocity) pre-/postprandial decreased in the bleeding group only (CI pre/ CI post 1.30+/-0.23 (no bleeding) vs. 0.86+/-0.29 (bleeding); p<0.01). Portal hypertensive gastropathy was not related to any of the portal flow parameters. The portal blood velocity increment was comparable in controls (65%) and patients with Child-Pugh class A cirrhosis (56%), but lower in patients with class B (32%) and class C cirrhosis (15%, p<0.05 vs. class A). Also, there was no postprandial decrease in congestion index in patients with the most severe cirrhosis (p<0.01 class C vs. class A and B). CONCLUSIONS: The postprandial rise in portal flow is inversely related to the severity of portal hypertension and liver cirrhosis, and may be a valuable parameter with respect to the risk of variceal bleeding.     

Distensibility of portacaval shunts in portal hypertensive cats: index of contractility model

Complete shunting of portal blood flow through portacaval shunts was obtained using a constrictor around the portal vein to gradually produce a total occlusion. After 4 weeks, acute experiments were conducted in anesthetized cats. Blood from the femoral artery was shunted through a pump to supply and control the entire portal blood flow. As shunted portal blood flow was varied over a wide range, the portal shunt resistance showed distensibility. Decreasing portal venous pressure from 15.0 +/- 0.9 to 11.1 +/- 0.6 mmHg (1 mmHg = 133.3 Pa) resulted in elevations of resistance of 58%. The relation between the resistance (R) and the distending pressure (Pd) was a constant, the index of contractility (IC), where IC = R.Pd3. In steady state, the IC was 485 +/- 55 mmHg4.mL-1.min.kg and did not change passively in response to changes in portal blood flow. In conclusion, portacaval shunts are passively distensible, and resistance is altered as a cubic function of the distending pressure. Because resistance is altered both actively and passively, the IC should prove useful to differentiate these alternatives for evaluation of changes in portal hypertensive therapy.     

Role of nitric oxide in the vasodilator response to mental stress in normal subjects

Vascular production of nitric oxide (NO) plays an important role in a variety of physiologic processes. This study examines the contribution of NO to the vasodilator response to mental stress. The effects of mental arithmetic testing on forearm vascular dynamics were analyzed in 15 normal subjects (9 men; age 45 +/- 12 years) during intraarterial infusion of either saline or N(G)-monomethyl-L-arginine (L-NMMA; 4 micromol/min for 15 minutes), an inhibitor of NO synthesis. The effect of L-NMMA on endothelium-independent vasodilation induced by intraarterial infusion of sodium nitroprusside was also studied in 11 of the 15 subjects. Forearm blood flow was measured by plethysmography. Mental stress increased forearm blood flow from 2.35 +/- 0.84 to 5.06 +/- 2.66 ml/min/dl (115%) during saline and from 1.72 +/- 0.59 to 2.81 +/- 0.99 ml/min/dl (63%) during L-NMMA infusion. The vasodilator effect of mental stress was significantly lower during L-NMMA infusion than during saline (1.1 +/- 0.65 vs 2.71 +/- 2.15 ml/min/dl; p = 0.01). L-NMMA administration did not significantly change mean arterial pressure and heart rate responses to mental stress. In contrast, the vasodilator effect of sodium nitroprusside (1.6 microg/min) was similar during infusion of L-NMMA and during saline (3.75 +/- 1.55 vs 2.85 +/- 1.38 ml/min/dl; p = 0.16). These findings indicate that local release of NO is involved in the forearm vasodilator response to mental stress.