Effect of interferon gamma on intrahepatic haemodynamics of the cirrhotic rat liver

Sublethal injury of the liver with carbon tetrachloride (CCI₄) induces the modulation of hepatic stellate cells to their myofibroblast (MFB) phenotype. Pretreatment or concomitant treatment with interferon gamma (IFNγ) has been shown to inhibit this phenomenon. The aim of this study was to investigate the influence of IFNγ treatment (50 000 IU s.c. each day for 5 days) in rats with an established cirrhosis. Cirrhosis was induced with nine doses of CCI⁴. Comparison of biopsies before and after treatment with IFNγ showed that the number of MFB present, identified by their α-smooth muscle actin immunoreactivity, was markedly reduced. Pressure-flow curves were constructed in isolated perfused liver preparations from IFNγ-treated and saline-treated cirrhotic rats and analysed to obtain the extrapolated zero-flow intercept (P⁰, an index of hepatic vascular distensibility) and the vasodilator-induced change in resistance at a flow rate of 1 mL/min per g (ΔR₁ an indication of the level of intrinsic vascular tone). In IFNγ-treated rats, portal venous pressure measured in vivo was significantly reduced compared with controls (11.9±1.2 vs 16.0 ± 0.5 mmHg, P < 0.05), P₀ was lower (2.03 ± 0.18 vs 2.87 ± 0.32 mmHg, P < 0.05) and ΔR₁ was decreased (0.39 ± 0.15 vs 1.02 ± 0.19 mmHg/mL per min per g, P < 0.05). The findings indicate that treatment with IFNγ is effective in reducing MFB density in established CCI₄-cirrhosis in the rat and results in a marked improvement in intrahepatic haemodynamics.     

Oral Administration of Nipradilol and the Acute and Chronic Splanchnic Hemodynamic Effects of a New β-Blocker with Nitrovasodilating Properties in Patients with Liver Cirrhosis

Objectives: We studied the effects of nipradilol, which has both a nonselective β-blocker action and a vasodilating action similar to nitroglycerin, on portal hypertension. Methods: We measured hepatic venous pressure gradient and splanchnic and systemic hemodynamics before beginning therapy, 2 h after an oral dose of 6 mg, and after either 6 months of nipradilol 6 mg twice a day (n = 14) or of a placebo (n = 6) in 20 cirrbotic patients. Results: No significant changes were observed after the administration of the placebo. Oral nipradilol induced a significant reduction in the hepatic venous pressure gradient (base line: 14.8 ± 3.2 mm Hg vs 2 h: 12.3 ± 3.4 mm Hg, p < 0.01; 6 mo: 12.5 ± 3.2 mm Hg, p < 0.05) without a significant change in the free hepatic venous pressure. The hepatic vascular resistance decreased signifi-cantly (base line: 1811 ± 778 dyn. sec. cm^-5 vs 2 h: 1540 ± 701 dyn. scc. cm^-5, p < 0.05; 6 mo: 1564 ± 693 dyn. sec. cm^-5, p < 0.05) without a significant change in hepatic blood flow. A decrease in the hepatic venous pressure gradient greater than 10% was observed in nine patients (64%), defined as "responders," at 2 h and in 10 patients (71%) at 6 months. The reduction of mean heart rate and hepatic venous pressure gradient in these responders was 16.2% and 28.3% at 2 h and 15.1% and 27.1% at 6 months, respectively. Conclusions: We found that in some cirrhotic patients, at the doses used in this study, long term oral nipradilol administration produces a reduction in the hepatic venous pressure gradient with both a β-blocking and a nitrovasodilating action.     

Systemic and portal haemodynamic changes following triglycyllysine vasopressin plus nitroglycerin administration in patients with hepatitis B-related cirrhosis

We measured the haemodynamic changes following triglycyllysine vasopressin administration and after addition of nitroglycerin in twelve patients with portal hypertension due to hepatitis B-related cirrhosis. A bolus i.v. injection of triglycyllysine vasopressin at a dose of 2 mg reduced the hepatic venous pressure gradient from 18.5 +/- 3.7 (mean +/- S.D.) to 15.6 +/- 4.0 mmHg, p less than 0.001. However, the cardiac index decreased from 4.8 +/- 1.0 to 3.7 +/- 0.8 l/min m2, p less than 0.001; the heart rate decreased from 79 +/- 15 to 71 +/- 13, p less than 0.01; the right atrial pressure increased from 3.2 +/- 1.9 to 5.3 +/- 2.3 mmHg, p less than 0.001; the mean arterial pressure increased from 92 +/- 13 to 103 +/- 13 mmHg, p less than 0.05; and the systemic vascular resistance rose from 939 +/- 182 to 1367 +/- 310 dyn/s cm-5, p less than 0.001. Furthermore, both mean pulmonary arterial pressure and pulmonary capillary wedge pressure showed a significant increase following triglycyllysine vasopressin administration as compared with baseline values (p less than 0.005). The addition of sublingual nitroglycerin at a dose of 0.6 mg returned all the systemic haemodynamic parameters to baseline levels. On the other hand, nitroglycerin administration caused no further change in the hepatic venous pressure gradient. We concluded that although triglycyllysine vasopressin significantly reduced portal pressure in patients with hepatitis B-related cirrhosis, it produced untoward systemic haemodynamic changes similar to those seen with vasopressin. The addition of nitroglycerin improved the detrimental systemic haemodynamic effects produced by triglycyllysine vasopressin without further reducing the hepatic venous pressure gradient.     

Gall-bladder wall thickening in patients with liver cirrhosis

Gall-bladder wall thickening is commonly seen in patients with cirrhosis, but its exact causes have not been well established. We evaluated clinical, biochemical and haemodynamic data of patients with cirrhosis with respect to the presence of thickening of the gall-bladder wall. After excluding patients who presented with gallstones, acute or chronic cholecystitis, heart failure, a serum creatinine level greater than 2 mg/dL and/or a serum alanine aminotransferase level greater than 400 U/L, 77 patients with cirrhosis (75 male, two female; mean age 58±8 years) were enrolled in the study. Clinical, biochemical, ultrasound and haemodynamic data were obtained in every patient. Fortyone (53%) of 77 patients with cirrhosis had gall-bladder wall thickening (>4mm). Compared with patients with a normal gall-bladder wall, patients with gall-bladder wall thickening had significantly lower serum albumin levels (3.6±0.6 vs 2.9±0.7 gm/dL, respectively; P< 0.05), a longer prothrombin time (13±6 vs 16±6s, respectively; P<0.05), more patients with Child-Pugh class C (6 vs 37%, respectively; P<0.05) and more patients with ascites (8 vs 50%, respectively; P<0.05). In addition, compared with patients with a normal gall-bladder wall, those patients with gall-bladder wall thickening had a higher hepatic venous pressure gradient (13.9±4.5 vs 17.1±4.1 mmHg, respectively; P<0.01) and a lower systemic vascular resistance (SVR; 1144±332 vs 1010±318 dyn.s/cm⁵, respectively; P< 0.05). Using a multivariate analysis, the presence of ascites and SVR lower than 900 dyn.s/cm⁵, were independently correlated with the presence of gall-bladder wall thickening, while a hepatic vein pressure gradient greater than 10 mmHg had only a marginally significant association. The presence of ascites, decreased SVR and portal hypertension are related to the occurrence of gall-bladder wall thickening in patients with cirrhosis, indicating that the development of gall-bladder wall thickening may be multifactorial.     

Size dependent platelet subpopulations: relationship of platelet volume to ultrastructure, enzymatic activity, and function

A method for the separation of platelets on the basis of their size has been developed using counterflow centrifugation. Platelets were separated, free of plasma proteins and other cells, into seven subpopulations. The smallest-sized platelets, designated as Fraction 1, had a mean platelet volume (MPV) of 3.94 ± 0.60 μm³ (SD). Each successive fraction had a progressively larger MPV. The MPV for the largest-sized platelets, designated Fraction 7, was 8.19 ± 0.64 μm³. The MPV for the original platelets prior to fractionation was 6.57 ± 0.61 μm³. The mean density of Fraction 1 platelets was 1.067 ± 0.002 g/cm³, while Fraction 7 had a mean density of 1.072 ± 0.001 g/cm³. Transmission electron microscopy demonstrated that Fraction 1 had 4.3 ± 0.9 dense bodies per platelet, and Fraction 7 had 12.6 ± 2.4 dense bodies per platelet. Platelet LDH activity showed that the Fraction 1 platelets had 4.77 ± 0.92 iu per 10¹⁰ platelets; Fraction 7 platelets had 14.88 ± 1.23 iu per 10¹⁰ platelets. The LDH activity in the platelets before separation into subpopulations was 9.47 ± 1.45 iu per 10¹⁰ platelets.     

Pathogenesis of distal renal tubular acidosis (incomplete form) in cirrhosis: Normal urinary Pco2 after bicarbonate loading

In liver cirrhosis, an associated defect in urinary acidification is well known but its pathophysiologic nature is not well defined. Recent studies suggest that the urine P co₂ during maximal alkalinization of the urine is an adequate index of distal hydrogen ion secretion. To evaluate the nature of distal renal tubular acidosis (distal RTA) in cirrhosis, the urine minus blood P co₂ gradient [(U – B) P co₂] in alkaline urine was determined in four patients with cirrhosis and distal RTA, and compared with that in four patients without distal RTA (control subjects), as well as with that in one patient with Sjögren's syndrome and distal RTA (subject with impaired distal acidification). As expected, the (U – B) P co₂ after sodium bicarbonate loading was low (10.6 mmHg) in the subjects with impaired distal acidification and normal (32.5 mmHg, s.e.m. = 4.8) in control subjects. By contrast, all four patients with cirrhosis and distal RTA were able to achieve a normal (U – B) P co₂ gradient (33.8 mmHg, s.e.m. = 4.0) after sodium bicarbonate loading, even in the presence of the defect in urinary acidification under acid loading. These results suggest that the pathophysiology of the urinary acidification defect in liver cirrhosis is distinct from that in ordinary distal RTA; the latter signifies a defect in H⁺ secretion (secretory or voltage-dependent RTA), whereas, in cirrhosis, an increased permeability for H⁺ may cause the inability to acidify the urine.     

Relationships between haemodynamic alterations and the development of ascites or refractory ascites in patients with cirrhosis

OBJECTIVE: In patients with cirrhosis, the relationships between haemodynamic alterations and the development of ascites or the occurrence of refractory ascites are unknown. The aim of the present study was to compare haemodynamic measurements obtained in patients with non-refractory ascites to haemodynamic measurements obtained in patients without ascites and in patients with refractory ascites. METHODS: A cohort of 121 patients was prospectively studied, of whom 29 patients did not have ascites, 45 had non-refractory ascites and 47 had refractory ascites. Splanchnic, renal and systemic haemodynamics were measured in all patients. RESULTS: The hepatic venous pressure gradient was significantly higher in patients with non-refractory ascites than in patients without ascites (18.5 +/- 0.8 mmHg versus 15.8 +/- 0.7 mmHg). Renal and systemic haemodynamics did not significantly differ between patients with non-refractory ascites and patients without ascites. The glomerular filtration rate and renal blood flow were significantly lower in patients with refractory ascites than in patients with non-refractory ascites (77 +/- 4 versus 107 +/- 5 ml/min and 867 +/- 62 versus 1,008 +/- 68 ml/min, respectively). Splanchnic and systemic haemodynamics did not significantly differ between patients with refractory ascites and patients with non-refractory ascites. CONCLUSIONS: In patients with cirrhosis, an increase in portal hypertension was the sole haemodynamic alteration related to the development of ascites. Renal vasoconstriction (and subsequent renal hypoperfusion and hypofiltration) was the only haemodynamic alteration related to the occurrence of refractory ascites. The development of ascites or refractory ascites was not associated with any alteration in systemic haemodynamics.     

Tissue hypoxia and hepatocellular insufficiency in patients with cirrhosis

To determine whether tissue hypoxia occurred in cirrhosis, oxygen contents, mixed venous and hepatic venous lactate concentrations as well as systemic hemodynamics were studied in 53 patients with cirrhosis. The influence of liver failure on tissue oxygenation was also studied. Cardiac index and mixed venous and hepatic venous lactate concentrations were significantly higher in patients with cirrhosis than in 20 control subjects. Oxygen consumption, oxygen extraction ratio and mixed venous and hepatic venous carbon dioxide tensions were significantly lower in the former than in the latter. Oxygen transport was not significantly different between the two groups. Cardiac index and oxygen transport were not significantly different between grade A (Pugh's classification) and grade C patients. Mixed venous as well as hepatic venous lactate concentrations were significantly higher while oxygen consumption, oxygen extraction ratio and carbon dioxide tensions were significantly lower in grade C than in grade A patients. We conclude that tissue hypoxia occurs in patients with cirrhosis and hepatic insufficiency. This tissue hypoxia might be due to arteriovenous shunting-related limitation of tissue oxygen extraction.     

Percutaneous Mitral Commissurotomy in Acute Pulmonary Edema

From January 1994 to July 1998, percutaneous mitral commissurotomy was performed in 520 patients. Of these patients, 7 (4 men and 3 women aged 31 ± 5.6 years) were dilated in an emergency situation of intractable pulmonary edema caused by severe mitral stenosis. Three patients required mechanical ventilatory support. Percutaneous mitral commissurotomy was performed with the Inoue balloon. The dilatation of the valve was undertaken even though the echocardiographic score of the valve was high. Percutaneous mitral commissurotomy resulted in an increase in the mitral valve area from 0.72 ± 0.18 cm² to 1.95 ± 0.18 cm² (P = 0.011) with a concomitant reduction in pulmonary artery systolic pressure from 82.5 ± 16.4 mmHg to 46.7 ± 11.6 mmHg (P = 0.018). One patient died (he had two cardiac arrests before the dilatation). During follow-up (mean 18 months), one patient presented with a restenosis, one an aggravation of mitral insuflciency grade, and four were in NYHA functional Class II. Thus, percutaneous mitral commissurotomy can be considered as a treatment of choice in patients with intractable pulmonary edema caused by severe mitral stenosis.     

Effect of anaemia on haemodynamics in patients with cirrhosis

BACKGROUND: It has been suggested that increased blood haemoglobin attenuates splanchnic vasodilatation in portal-hypertensive rats by nitric oxide inactivation. However, the haemodynamic effect of anaemia in cirrhotic patients of varying severity has been rarely discussed. The aim of this study was to evaluate the influence of anaemia on systemic and splanchnic haemodynamics in cirrhotic patients of differing severity. METHODS: Two hundred and twenty-five cirrhotic patients were included in this study. All biochemical and haemodynamic results were utilized for analysis. Anaemia was defined as a haemoglobin level below the cut-off value of 12 g/dL, which might best predict low systemic vascular resistance. RESULTS: Compared with non-anaemic patients, anaemic patients had decreased mean arterial pressure (90 +/- 1 vs 95 +/- 1 mmHg, P = 0.002), and decreased systemic vascular resistance (1022 +/- 25 vs 1227 +/- 30, P < 0.0001), and increased cardiac index (4.3 +/- 0.1 vs 3.8 +/- 0.1 L/min per m2, P < 0.0001) and increased hepatic venous pressure gradient (16.7 +/- 0.5 vs 14.4 +/- 0.6 mmHg, P = 0.006). Haemoglobin concentration exerted an influence on the degree of vasodilatation in cirrhotic patients, with Child-Pugh's A class (but not in Child-Pugh's B and C classes), and in patients without ascites (but not in patients with ascites). CONCLUSIONS: It was concluded that anaemia has a negative effect on hyperdynamic circulation in patients with early cirrhosis which is not observed in patients with advanced cirrhosis.     

The role of the liver in the metabolism of neurotensin-like immunoreactivity in man and dog

Abstract To assess the role of liver in the metabolism of neurotensin-like immunoreactivity (NTLI) basal and meal-stimulated levels of plasma NTLI were measured by radioimmunoassay, employing a specific C -terminal antiserum in: healthy control subjects; patients with cirrhosis of the liver who had previously undergone a portacaval shunt; and patients with cirrhosis of the liver and hepatic failure, without a portacaval shunt. Neurotensin (1–13) was infused into the portal vein of the dog for 60 min, at a dose of 100 pmol/kg per min, and blood sampled simultaneously from the portal, hepatic and peripheral venous systems to determine the hepatic extraction and clearance of NTLI. The results revealed that: the liver is a major site of neurotensin metabolism; transhepatic extraction of exogenous neurotensin was 39%; hepatic clearance of NTLI was about 13 ml/kg per min and the total metabolic clearance of NTLI was 36.8 ml/kg per min (s.e.m. = 4.8) and the t_½ of NTLI was 2.8 min.     

Endothelin-induced vasoconstriction in isolated perfused liver preparations from normal and cirrhotic rats

Isolated, perfused rat liver preparations (IPRL), obtained from rats with carbon tetrachlorideinduced cirrhosis and normal controls, were used to investigate responses to the vasoactive peptide endothelin-1 (ET-1). The mean perfusion resistance (R) of cirrhotic IPRL was significantly greater than that of controls (2.63 ± 0.24 vs 1.54 ± 0.14 mmHg/mL per min per g; P < 0.01). Both control and cirrhotic IPRL demonstrated a concentration-related increase in resistance (ΔR) in response to ET-1, with a minimum effective concentration of approximately 3 × 10⁻¹¹ mol/L. The EC₅₀ (-log of the 50% effective concentration) was not significantly different between cirrhotic and control IPRL (8.48 ± 0.19 and 8.79 ± 0.11, respectively); however, the maximum response to ET-1 was significantly greater in cirrhotic preparations (R: 10.4 ± 2.2 vs 4.4 ± 0.5 mmHg/mL per min per g, P < 0.01; DR, 7.8 ± 2.1 vs 2.8 ± 0.4 mmHg/mL per min per g, P < 0.01). Following maximal stimulation by ET-1, the mean portal-hepatic venous pressure gradient at a physiological flow rate of 1 mL/min per g was approximately 90% greater across cirrhotic IPRL than that across normal IPRL (11.2 ± 2.0 vs 5.9 ± 0.9 mmHg, respectively; P < 0.05). These results support the hypothesis that endogenously released ET-1 has a significant influence on the portal vascular resistance of cirrhotic liver in vivo and has an important role in the pathogenesis of portal hypertension.     

Endothelin-1 contributes to maintenance of systemic but not portal haemodynamics in patients with early cirrhosis: a randomised controlled trial

BACKGROUND AND AIMS: Increased endothelin (ET)-1 activity may contribute to the complications of cirrhosis and portal hypertension. The aim of this study was to assess the systemic and portal haemodynamic effects of selective ET-A and ET-B receptor antagonism in patients with cirrhosis. METHODS: Sixteen patients with cirrhosis and portal hypertension (aged 52 (1) years, Pugh score 6.2 (0.3)) underwent 24 studies with infusions of: (A) selective ET-A antagonist, BQ-123 (n = 8), at 1000 and 3000 nmol/min; (B) selective ET-B antagonist, BQ-788 (n = 8), at 100 and 300 nmol/min; or (C) matched saline placebo (n = 8) in a double blind randomised manner. Haemodynamic measurements were performed through pulmonary artery, hepatic venous, and femoral artery catheters. RESULTS: Baseline patient characteristics were well matched. Compared with placebo, BQ-123 decreased mean arterial pressure (MAP -15 (11) mm Hg (-18%); p<0.02) and pulmonary vascular resistance index (PVRI -81 (54) dyn x s x m2/cm5 (-64%); p<0.05), with no effect on hepatic venous pressure gradient (HVPG), cardiac index (CI), or systemic vascular resistance index (SVRI). Compared with placebo, BQ-788 increased MAP (+11 (3) mm Hg (+12%); p<0.03) and SVRI (+1101 (709) dyn x s x m2/cm5 (+50%); p<0.05), reduced CI (-1.0 (0.4) l/min/m2 (-29%); p = 0.05) with no effect on HVPG or PVRI. CONCLUSIONS: ET-1 contributes to maintenance of systemic and pulmonary haemodynamics without acutely affecting HVPG in patients with early cirrhosis. In this group of patients, the use of selective ET-A and ET-B antagonists for the management of variceal haemorrhage is likely to be limited.     

Effect of beta-adrenergic blockade on elevated arterial compliance and low systemic vascular resistance in cirrhosis.

BACKGROUND: Patients with cirrhosis exhibit a characteristic hyperdynamic circulation with increased cardiac output and heart rate and reduced systemic vascular resistance. The compliance of the arterial tree has recently been reported to be increased in these patients, who are often treated with beta-blockers, but the effect of this treatment on arterial compliance has not been investigated. The aim of the present study was therefore to assess the effects of propranolol on the arterial compliance of patients with cirrhosis. METHODS: Twenty patients with cirrhosis underwent a haemodynamic investigation with determination of splanchnic and systemic haemodynamics. Arterial compliance was determined as the ratio of the stroke volume to the pulse pressure and compared to normal values. RESULTS: All the patients had significant portal hypertension, with a mean hepatic venous pressure gradient (HVPG) of 17.8 mmHg, and responded to beta-blocker treatment with a significant reduction in the HVPG (-16%; P < 0.001). Arterial compliance was elevated (1.27 versus controls 1.01 ml/mmHg; P < 0.001), but remained almost unchanged during beta-adrenergic blockade (1.27 versus 1.29 ml/mmHg, +2%, ns), whereas systemic vascular resistance increased substantially (1083 versus 1378 dyn x s x cm-5, +27%; P < 0.001). The mean arterial blood pressure (-6%; P < 0.05), heart rate (-20%; P < 0.001), cardiac output (-25%; P < 0.001) and hepatic blood flow (-22%; P < 0.001) fell significantly. CONCLUSIONS: Treatment with beta-blockers increases small vessel (arteriolar) vascular tone towards the normal level, but does not affect the elevated compliance of the larger arteries in patients with cirrhosis.     

Mitral Balloon Valvuloplasty as an Outpatient Procedure Using Inoue Balloon Technique

Objective: To evaluate the safety and feasibility of mitral balloon valvuloplasty (MBV) as an outpatient procedure. Background: MBV is usually done as an inpatient procedure, requiring 3–4 days of hospital admission. Only one report is available about MBV as a day case procedure in the English literature. Methods: Between October 1994 and December 1996, 128 patients underwent MBV using an Inoue balloon. Of those, 31 patients (Group I) had the procedure as outpatients and 97 patients (Group II) as inpatients. Their mean age in Group I was 29 ± 9 years and in Group II 32 ± 10 years (P < 0.3). Atrial fibrillation was present in 4 patients in Group I and in 13 patients in Group II (P < 0.99). Results: Hemodynamic study revealed that mitral valve area increased from 0.9 ± 0.2 to 1.9 ± 0.5 cm²* in Group I and from 0.8 ± 0.2 to 1.7 ± 0.5 cm²* in Group II, Left atrial pressure decreased from 24 ± 5 to 15 ±6 mm Hg* in Group I and 24 ± 6 to 16 ± 5 mmHg in Group II.* Mitral valve gradient decreased from 15 + 5 to 5 + 2 mmHg in Group I and 15 + 5 to 6 + 3 mmHg in Group II* (*P < 0.001). Patients in Group I stayed in the Preadmission Unit for a mean period of 9.5 ± 2.5 hours. Patients in Group II stayed for a mean of 2.5 days in the hospital. Severe mitral regurgitation developed in one patient in each Group and needed semiurgent mitral valve replacement without sequela. No death, convulsions, or thromboembolism were encountered, and three patients in both Groups developed minor hematoma and needed no additional treatment. Conclusion: MBV as an outpatient procedure is feasible and safe and could significantly decrease the cost of medical care.     

A 3-month course of long-acting repeatable octreotide (sandostatin LAR) improves portal hypertension in patients with cirrhosis: a randomized controlled study

OBJECTIVE: In patients with cirrhosis, acute octreotide administration may transiently decrease the hepatic venous pressure gradient (HVPG). Information on long-term effects of octreotide is limited and controversial. We evaluated portal and systemic hemodynamics following a prolonged administration of long-acting octreotide in patients with cirrhosis. METHODS: Eighteen cirrhotic patients (alcoholic 12; age 55 yr [44-69]; Pugh's score 7.8; HVPG 17.3 mmHg [12-22]), no steatohepatitis on histology, were randomized to intramuscular octreotide 20 mg (group A) q 4 wk for 3 months or placebo (group B) in a double-blind fashion. At baseline and 3 months, we measured the HVPG, systemic hemodynamics, endothelin-1 (ET-1), and vascular endothelial growth factor (VEGF) in hepatic venous blood. RESULTS: Patients remained compensated except for one episode of infection in each group. At 3 months, the HVPG decreased in group A but not in group B (16.5 +/- 1.3 to 11.8 +/- 1.5 mmHg, P < 0.01; 18.2 +/- 1 to 17 +/- 1.1 mmHg, P= 0.4). Systemic hemodynamics and liver function remained unchanged. In group A, but not in group B, VEGF decreased (21.2 +/- 4.7 to 13.7 +/- 3.5 pg/mL, P < 0.01; 22.5 +/- 7.8 to 19.2 +/- 5.4 pg/mL, P= 0.4). ET-1 remained stable. Changes in HVPG and VEGF were correlated (r = 0.49, P < 0.05). CONCLUSIONS: Three months of long-acting octreotide in selected cirrhotic patients with portal hypertension decreases the HVPG independent of systemic hemodynamics and liver function. The decrease in VEGF blood levels suggests an improvement in splanchnic hyperemia.     

Antithrombin III transfusion in patients with hepatic cirrhosis

S ummary . This study was designed to examine the effect of selective correction of antithrombin III activity on the increased turnover of fibrinogen, which occurs in patients with liver cirrhosis supposedly due to disseminated intravascular coagulation. Human antithrombin III concentrates were therefore transfused in seven patients with cirrhosis and antithrombin III deficiency (<80%). Fibrinogen half-life and the fractional catabolic rate constant were calculated from the turnover of ¹²⁵I-fibrinogen which was represented by a two-compartment model. Prior to antithrombin III transfusion, ¹²⁵I-fibrinogen half-life was 76.7 ± 15.2 h and the fractional catabolic rate constant was 0.33 ± 0.11 of the plasma fibrinogen pool per day. In six healthy adult controls these values were significantly different: 109.4 ± 8.8 h and 0.19 ± 0.01 respectively. Correction of antithrombin III activity with human antithrombin III concentrate reduced the increased turnover of radiolabelled fibrinogen to normal. The ¹²⁵I-fibrinogen half-life became 108.4 ± 17.6 h and the fractional catabolic rate constant decreased to 0.23±0.06. These observations indicate that decreased antithrombin III activity contributes in an important way to the increased ¹²⁵I-fibrinogen turnover in patients with cirrhosis and this might reflect intravascular coagulation.     

Irbesartan plus low-dose propranolol versus low-dose propranolol alone in cirrhosis: a placebo-controlled, double-blind study

OBJECTIVES:  Angiotensin II receptor antagonists have been shown to moderately lower portal pressure in some patients with cirrhosis but may have adverse effects on kidney function. This study aimed at comparing the effects of a combined treatment using irbesartan plus propranolol with propranolol monotherapy on portal pressure and kidney function in patients with cirrhosis.
METHODS:  Thirty-two patients were included (Child A/B/C: 13/18/1, etiology: 16 alcohol, 13 viral, 3 other; bilirubin 1.4 ± 1.1 mg/dL, creatinine 0.86 ± 0.20 mg/dL, baseline hepatic venous pressure gradient 18.7 ± 5.3 mmHg). All patients received 20 mg propranolol b.i.d. Additionally, they randomly received either placebo (N = 15) or irbesartan (step-up dosage titration up to 300 mg/d, N = 17). Patients were followed at weekly intervals, re-evaluation of hepatic venous pressure gradient (HVPG) was performed after 8 wk.
RESULTS:  One patient in the propranolol/irbesartan group was excluded due to variceal bleeding. No other adverse events occurred. Portal pressure declined in both groups (propranolol/irbesartan group 19.6 ± 1.5 mmHg to 16.6 ± 1.2 mmHg, P = 0.037, propranolol/placebo group 17.8 ± 1.1 mmHg to 15.1 ± 1.2 mmHg, P = 0.019). Sodium excretion significantly increased in the propranolol/irbesartan group (from 122 ± 20 mmol/d to 230 ± 23 mmol/d, P = 0.045), but not in the propranolol/placebo group.
CONCLUSIONS:  Combination treatment of propranolol plus irbesartan is well tolerated in cirrhotic patients when titrating the angiotensin II antagonist in a step-up manner, and it increases sodium excretion in patients with compensated or moderately decompensated cirrhosis. Addition of irbesartan has no effect on portal pressure.     

Percutaneous transseptal mitral valvotomy-progress report

Background : Percutaneous transseptal mitral valvotomy (PTMV) has been established as an alternative to surgery in the treatment of mitral stenosis.
Aim : To review our experience in the first 200 attempted PTMV procedures in patients with mitral stenosis, and the short and medium term follow-up.
Methods : PTMV was attempted on 200 occasions in 189 patients with significant mitral stenosis between May 1988 and May 1994. There were 156 females and 33 males, mean age 53.5 years (range 14 to 83 years). Six patients were pregnant at the time of the procedure.
Results : Valve split was achieved at the initial attempt in 183/189 procedures (97%). Clinical improvement of at least one New York Heart Association (NYHA) functional class was achieved in 172/189 patients (91%). The mean mitral valve gradient (mean±SD) decreased from 11.5±5.1 mmHg to 4.9±4.1 mmHg, mean cardiac output rose from 3.9±1.1 L/minute to 4.4±1.4 L/minute and mean calculated mitral valve area increased from 1.0±0.3 cm² to 2.1±0.9 cm². Ten patients developed clinically significant mitral incompetence requiring surgical mitral valve replacement. There were two transient cerebral embolic events. Small atrial septal defects were detected echocardio-graphically in 42 patients, but none has been a clinical problem. There were no early deaths; there were 11 late deaths, four of which were non-cardiac. Twenty patients have had repeat PTMV for re-stenosis, four to 67 months after the first.
Conclusions : PTMV provides significant haemodynamic and clinical improvement with low risk and should be considered the treatment of choice in patients with mitral stenosis.     

Systemic Hemodynamic Changes in Elderly Hypertensive Patients After Ingesting Foods With Lipid, Protein, and Carbohydrate Contents

Aging is associated with changes in cardiovascular structure and function, which predisposes elderly people to reduced blood pressure levels after meals. The authors studied cardiac systolic function in elderly hypertensive patients after eating meals with different contents of lipids, proteins, and carbohydrates. Ten elderly male hypertensive patients were studied (mean age, 69 years; range 60–80 years). No patients had a previous history of orthostatic or postprandial hypotension. Patients ate 1 of 3 pre-prepared meals: lipid meal (LM), protein meal (PM), or carbohydrate meal (CM), on different days. Mean arterial pressure, total peripheral resistance index (TPRi), cardiac index (CI), and stroke index were recorded at the end of the fasting period and then at 5, 15, 30, 45, and 60 minutes after food ingestion. After ingestion of a CM, the CI increased from 2.30±0.21 L/min/m² to 2.61±0.24 L/min/m² and the TPRi decreased from 3212±226 dynes/sec² to 2793±255 dynes/sec² at 45 minutes (P<.05). After the LM, the CI increased from 2.15±0.15 to 2.84±0.27 L/min/m² and the TPRi decreased from 3630±274 L/min/m² to 2666±282 dynes/sec² at 45 minutes (P<.05). After the PM, no systemic hemodynamic changes were observed. When all 3 meals were compared, the highest values of CI and the lowest values of TPRi were observed for the LM and CM. The authors' results show that fat- and carbohydrate-rich foods cause changes in the systemic hemodynamic of the elderly hypertensive patients.