Relationships between the severity of cirrhosis and haemodynamic values in patients with cirrhosis

Abstract The relationship between the severity of cirrhosis and systemic and hepatic haemodynamic values was evaluated in 193 patients with cirrhosis, most of whom were diagnosed with post-necrotic cirrhosis. It was found that the hepatic venous pressure gradient and cardiac output in Pugh's A patients (13.6 ± 4.8 mmHg and 6.2 ± 1.6 L/min, mean ± s.d.) were significantly lower than in both Pugh's B (16.8 ± 4.3 mmHg and 7.3 ± 2.1 L/min) and Pugh's C (18.8 ± 5.5 mmHg and 7.4 ± 2.3 L/min) patients ( P < 0.01), respectively. In contrast, the systemic vascular resistance in Pugh's A patients (1232 ± 369 dyn/s per cm⁵) was significantly higher than in both Pugh's B (1016 ± 345 dyn/s per cm⁵) and Pugh's C (935 ± 234 dyn/s per cm⁵) patients ( P < 0.01), respectively. Additionally, not only was there a positive correlation found between Pugh's score and cardiac output and hepatic venous pressure gradient, but a negative correlation was found between Pugh's score and systemic vascular resistance. It was also confirmed that the degree of portal hypertension and the hyperdynamic circulation were more severe in patients with ascites than in those without ascites. However, there were no statistically significant differences in hepatic venous pressure gradient among patients with F1, F2 and F3 esophageal varices (15.7 ± 4.0, 17.0 ± 4.8 and 18.0 ± 4.8 mmHg, respectively). It is concluded that in those patients with cirrhosis, the severity of cirrhosis is closely related to the degree of the hyperkinetic circulatory state and portal hypertension.     

Prognostic Significance of Hepatic Venous Pressure Gradient in Medically Treated Alcoholic Cirrhosis: Comparison to Aminopyrine Breath Test

In a long-term survival study, we compared the prognostic significance of the hepatic venous pressure gradient and of the aminopyrine breath test (ABT) in 99 alcoholic cirrhotic patients. Thirty patients survived and had a complete follow-up for at least 4 yr. Mean hepatic venous pressure gradient was 19.1 ± 5.8 mm Hg (range 8–35 mm Hg). Variceal rupture occurred only when the gradient was ±12 mm Hg. Variceal bleeding was observed exclusively in patients with large varices. Survival was not influenced by the level of gradient. We used the ABT to classify patients into three groups (group I, ABT ± 2%; group II, 1%± ABT < 2%; and group III, ABT < 1%). Survival was significantly higher in group I than in group II ( p < 0.05) or III ( p < 0.01), indicating a better prognosis at a residual functional hepatic cellular mass of about 50% of the lower limit of normal value.     

Endogenous Gastrin Release and Antral Gastrin Concentration in Gastroesophageal Reflux Patients and Normal Subjects

In this study we compared both endogenous gastrin release to a known gastrin stimulant, phenylalanine, and fasting antral mucosal gastrin concentration in normal subjects and patients with documented gastroesophageal reflux. Resting lower esophageal sphincter pressure in the reflux patients (14.7 ± 1.5 mm Hg) was significantly less ( p < 0.01) than in the normal subjects (27.5 ± 2.7 mm Hg). Basal serum gastrin concentrations were similar in the two groups. There were significant ( p < 0.05) increases in peak serum gastrin in response to intragastric administration of phenylalanine in both normal subjects (20.6 ± 6.7 pg/ml, p < 0.05) and refluxers (22.4 ± 3.0 pg/ml, p < 0.01) but there were no significant differences in these responses between normals and refluxers. Mean integrated gastrin response to phenylalanine in the reflux patients (812 ± 116 PG ml⁻¹ h⁻¹) was slightly higher than that in normals (609 ± 328 pg ml⁻¹ h⁻¹) although the difference was not significant. Antral gastrin concentration was slightly higher in reflux patients (15.7 ± 2.2 ng/mg tissue) than in normals (10.4 ± 4.2 ng/mg tissue), although this difference was not significant. There was no correlation between antral gastrin concentration and either integrated serum gastrin response or gastric acid output. We conclude that there is no difference between patients with gastroesophageal reflux and normal subjects with regard to serum gastrin levels, endogenous gastrin release, or antral gastrin concentration. These observations suggest no role for gastrin in the mediation of lower esophageal sphincter incompetence or the pathophysiology of gastroesophageal reflux.     

Correlation between platelet blood levels and the hepatic venous pressure gradient among patients with cirrhosis

BACKGROUND: Determination of hepatic venous pressure gradient is the main method used to assess portal pressure. Recently, platelet blood levels has been indicated as a non-invasive marker of the presence of portal hypertension. AIM: To correlate platelet blood levels with the hepatic venous pressure gradient among patients with cirrhosis. PATIENTS AND METHODS: A total of 83 cirrhotic patients who had undergone hepatic venous pressure gradient over the last 6 years were included. Patients were divided in groups according to Child-Pugh classification. All had upper digestive endoscopy to assess the presence of esophageal varices and platelet serum levels were recorded. RESULTS: Platelet serum levels range varied between 45,000/mm(3) and 389,000/mm(3) (mean: 104,099; standard deviation: 58,776). Mean hepatic venous pressure gradient was 15.2 mm Hg with a standard deviation of 6.4 mm Hg (range: 1 to 29 mm Hg). Simple linear regression analysis was applied to verify an association of hepatic venous pressure gradient and platelet serum levels, revealing a weak correlation between both variables. We observed a progressive reduction of serum platelet levels as esophageal varices diameter increased and hepatocellular function (established by Child-Pugh classification) decreased. However, these findings did not reach statistical significance. CONCLUSION: Despite the lack of a statistical significant correlation among serum platelet levels and hepatic venous pressure gradient or hepatocellular function, there was a clear tendency indicating that those variables could be involved in the pathogenesis of low platelet levels.     

Portal pressure response to losartan compared with propranolol in patients with cirrhosis

OBJECTIVES: Losartan, an angiotensin II receptor blocker, has portal hypotensive effects. This study evaluates the effect of losartan on portal pressure after 14 days and compares it with that of propranolol. METHODS: A total of 39 individuals with cirrhosis were randomized into two groups of 19 and 20 patients each and were treated with losartan and propranolol, respectively. Hepatic venous pressure gradient was measured at baseline and on day 14 of therapy. Responders to therapy had hepatic venous pressure gradient reduction of >/=20% of baseline value. RESULTS: With losartan, 15 of 19 (78.94%) patients were responders and with propranolol, nine of 20 (45%) patients were responders (p < 0.05). Although the hepatic venous pressure gradient reduction (i.e., percentage from baseline) with losartan (26.74 +/- 21.7%) was higher than with propranolol (14.52 +/- 32%), the difference was not significant. The reduction in hepatic venous pressure gradient with losartan was contributed mainly by a significant drop of wedge hepatic venous pressure from 32.42 +/- 6.61 mm of Hg to 28.31 +/- 5.09 mm of Hg (p < 0.05) compared to that with propranolol, which was from 34.55 +/- 5.41 mm of Hg to 32.75 +/- 8.13 mm of Hg (p > 0.05). Responders among alcohol-abusing patients were significantly higher with losartan (81.8%) compared to those on propranolol (27.2%; p < 0.05). In the losartan group, all seven nonascitic cirrhotic individuals, as compared with two of five in the propranolol group, responded to the drugs. During the study, no significant side effects were observed in either group (who were not receiving diuretics) or in follow-up with diuretics. CONCLUSIONS: Losartan is as effective as propranolol in reducing portal pressure in cirrhotic patients who are not receiving diuretics. Losartan is also superior to propranolol for achieving target level hepatic venous gradient for prevention of variceal bleeding in nonascitic and alcohol-abusing cirrhotic patients.     

Electrocardiographic Changes Following Balloon Dilatation of Valvar Pulmonic Stenosis

The purpose of this paper was to study the electrocardiographic changes following balloon pulmonary valvuloplasty for pulmonic stenosis and to see if such changes reflect improvement in pulmonary valve gradient following balloon valvuloplasty. Forty-one patients, ages 7 days to 20 years, underwent balloon valvuloplasty for severe valvar pulmonic stenosis. In 35 of these patients ECGs were available 3 to 34 months (mean 11) following valvuloplasty and were compared with pre-valvu-loplasty electrocardiograms. In 30 children with excellent relief of pulmonic stenosis (group I), frontal plane mean QRS vector moved toward the left from 127 ±25° to 81 ±47°as did the horizontal plane mean QRS vector, 88 ± 36° to 27 ±51°. The amplitude of R wave in V_1, 19 ± 11.6 mm, and V₂, 19.7 ± 12.2 mm, decreased respectively to 9.5 ± 5.9 mm and 11.3 ±6.1 mm. S wave amplitude in V₅ and V₆ also decreased. The improvement in the electrocardiogram is associated with a decrease in pulmonary valve gradient from 95 ± 50 to 29 ± 23 mm Hg. In five children with significant residual pulmonary valve gradient (group II), the electrocardiograms did not show any significant change. Evaluation of the time course of ECG changes in group I revealed that recognizable electrocardiographic improvement was first observed at 6 months following successful balloon pulmonary valvuloplasty. Normal electrocardiogram suggests minimal residual pulmonary valve gradient while right ventricular hypertrophy suggests significant residual obstruction unless the electrocardiogram was recorded at or before six months following balloon valvuloplasty. These data suggest that electrocardiogram is a good indicator of improvement following balloon pulmonary valvuloplasty. (J. Interven Cardiol 1988:1:3)     

Postprandial changes in portal haemodynamics in patients with cirrhosis.

Previous studies have shown that portal venous pressure increases in patients with cirrhosis after a protein meal. Since this increase may be mediated by an increase in hepatic blood flow or postsinusoidal hepatic vascular resistance, the present study was designed to examine the precise relation between the postprandial changes in these three variables in patients with cirrhosis and portal hypertension. Estimated hepatic blood flow (EHBF; indocyanine green clearance), portosystemic gradient (PSG; wedged free hepatic venous pressure), and postsinusoidal hepatic vascular resistance (PSR = PSG/EHBF) were measured simultaneously before and at 10 minute intervals after a high protein meal, containing 80 g protein, 40 g carbohydrate and 12 g fat (600 kcal) in nine patients (seven alcoholic, two non-alcoholic) with cirrhosis and portal hypertension. After the meal, the portosystemic gradient increased by 33% from mean (SEM) 15.6 (0.9) mm Hg to 20.7 (1.3) mm Hg, (p less than 0.01; Wilcoxon signed ranks test) within 30 minutes. Coincident with this increase in portosystemic gradient, estimated hepatic blood flow increased by 69.2% from 20.1 (1.7) ml/min/kg to 33.9 (2.5) ml/min/kg (p = 0.01), peak values occurring at 25 minutes, at which time the postsinusoidal hepatic vascular resistance had decreased by 31% from 1.10 (0.1) 10(-2) mm Hg/ml/min to 0.8 (0.5) 10(-2) mm Hg/ml/min (p = 0.01). These results suggest that the postprandial increase in portal venous pressure in patients with cirrhosis is mediated by an increase in hepatic blood flow and modified by a simultaneous decrease in postsinusoidal resistance.     

Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: a double-blind, placebo-controlled study.

The aim of this study was to determine the effects of the long-acting somatostatin analog, octreotide, on portal venous pressure and collateral blood flow in cirrhotic patients with portal hypertension during fasting and postprandial states. In a double-blind, placebo-controlled study, we investigated the effects of octreotide on the hepatic venous pressures and azygos blood flow of 21 patients before and after a standard liquid meal containing 40 gm of protein in 250 ml. Octreotide significantly reduced azygos blood flow from a mean of 499 +/- 65 ml/min to a mean of 355 +/- 47 ml/min (p < 0.01), but it had no effect on the hepatic venous pressure gradient. The hepatic venous pressure gradient of patients in the placebo group increased significantly, from a fasting mean of 16.4 +/- 1.6 mm Hg to a mean of 20.0 +/- 1.7 mm Hg 30 min after the meal (p < 0.01). In a second protocol hepatic venous pressures were measured in 20 patients at 30-min intervals for 2 hr after ingestion of the mixed meal. Again the placebo group showed a significant increase in the hepatic venous pressure gradient 30 min after the meal (20.4 +/- 1.5 mm Hg vs. 18.2 +/- 1.2 mm Hg; p < 0.05), but the group receiving octreotide showed no significant changes during the 2 hr of observation. We conclude that octreotide significantly reduces azygos blood flow, with little effect on portal venous pressure, and that it appears to inhibit postprandial increases in portal pressure in cirrhotic patients with portal hypertension.     

Effects of Alcohol on Experimental Atrial Fibrillation

The association of alcohol abuse, especially binge drinking, and atrial fibrillation, recently termed "holiday heart," has been recognized for some time. The effects of alcohol on atrial fibrillation, however, have not been studied. Accordingly, measurements of hemodynamics and duration of electrically induced atrial fibrillation were made in α-chloralose anesthetized dogs during the 30 min before and during a 30-min intravenous infusion of 1.7 g/kg of ethanol (25%, v/v), which produced an average infusion concentration of 254 ± 21 mg/dl. Average cardiac output, left ventricular (LV) peak dp/dt, and pulmonary artery mean pressure did not change, whereas LV systolic (116 ± 8 to 107 ± 9 mm Hg, p < 0.05) and aortic mean (95 ± 7 to 87 ± 9 mmHg, p < 0.05) pressures decreased. Heart rate and atrioventricular conduction in sinus rhythm, and atrial and ventricular activity in atrial fibrillation also did not change. Despite a decrease in arterial pH, duration of atrial fibrillation decreased (356 ± 143 to 93 ± 38 sec, p < 0.05). Moreover, at 15 min, when average ethanol concentration was 208 ± 20 mg/dl, and aortic mean pressure (95 ± 7 to 85 ± 8 mm Hg, p < 0.05), pulmonary artery mean pressure (16 ± 2 to 14 ± 2 mm Hg, p < 0.05), and LV peak dp/dt (1563 ± 143 to 1285 ± 167 mm Hg-sec⁻¹, p < 0.05) were reduced, duration of atrial fibrillation was less than control (356 ± 143 to 114 ± 56 sec, p < 0.05). Thus, at blood levels of ethanol in which the vasodilatory and myocardial depressant effects of ethanol are evident, alcohol has an antiatrial fibrillatory effect.     

Does Portal Hypertension Modify Colonic Mucosal Vasculature? Quantification of Alteration by Image Processing and Topology

Objective: Endoscopic images of the colonic mucosal venous structure in eight cirrhotic patients with esophageal varices and in eight noncirrhotic subjects were analyzed to qualitatively determine whether or not the vasculature be altered by persisting portal hypertension.
Methods: On the endoscopic images, a venous network consisting of confluent venous branches draining into one penetrating vein was as a whole defined as one "venous unit". For each venous unit, the area of vein bed was calculated by means of an image processor. Each venous network was idealized to be a graphic representation consisting of lines (venous routes) and dots (origins, terminations, branching or anastomosing), on which two topological variables, the total number of zero-dimensional cells (a0) and the Betti number of dimension-1 (β₁[K]) signifying the complexity and the number of venous anastomoses, respectively, were determined.
Results: The area of vein bed (mean ± SD) was significantly greater ( p < 0.01) for the cirrhotic patients (41 ± 37 mm²) than for the noncirrhotic subjects (24 ± 12 mm²). The a0 was also greater ( p < 0.01) for the patients (68 ± 29) than for the noncirrhotic subjects (42 ± 17). The β₁[K] for the patients was significantly greater ( p < 0.01) for the cirrhotic subjects (7.1 ± 4.4) than for the noncirrhotic subjects (2.6 ± 2.9).
Conclusion: The image processing and topological analysis of the colonic mucosal veins demonstrated that persistent portal hypertension alters the colonic mucosal venous structure by increasing the caliber of the veins and the number of merges (branching or anastomosing) between them.     

Hyposensitivity to vasopressin in patients with hepatitis B-related cirrhosis during acute variceal hemorrhage

It has been suggested that vasopressin given during hemorrhage may be less effective than when given during a stable state in a portal-hypertensive rat model. This study was designed to evaluate the hemodynamic response to vasopressin infusion in 25 HBsAg-positive cirrhotic patients. Nine patients had active variceal hemorrhage before vasopressin infusion, and the other 16 patients were in a stable condition at the time of infusion. The two groups of patients were similar in baseline values except that a higher heart rate was found in patients with hemorrhage (96 +/- 20 vs. 73 +/- 10 beats/min, mean +/- S.D., p less than 0.01). Thirty minutes after vasopressin infusion (0.66 units/min), hepatic venous pressure gradient significantly decreased in both bleeding and stable patients (from 21 +/- 9 to 18 +/- 9 mm Hg, p less than 0.05; and from 18 +/- 4 to 8 +/- 3 mm Hg, p less than 0.0001, respectively). However, the decrease of hepatic venous pressure gradient was less obvious in bleeding patients as compared with stable patients (4 +/- 3 vs. 9 +/- 2 mm Hg, p less than 0.0001). A significant reduction of hepatic venous pressure gradient after vasopressin infusion was found in five bleeding patients without shock (from a median of 16 mm Hg [range = 12 to 26] to 11 mm Hg [range = 6 to 18], p less than 0.05), but not in four bleeding patients with shock (from 28 [range = 15 to 36] to 25 [range = 18 to 33] mm Hg, p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of vasopressin on the intravariceal pressure in patients with cirrhosis: comparison with the effects on portal pressure

The present study investigated to what extent measurements of wedged and free hepatic venous pressures adequately reflect the effects of vasopressin at the esophageal varices in patients with cirrhosis. Eleven patients undergoing therapeutic sclerotherapy were studied by measuring wedged hepatic venous pressure, intravariceal pressure, free hepatic venous pressure, superior vena cava pressure and the intravascular pressure gradients wedged hepatic venous pressure-free hepatic venous pressure and intravariceal pressure-superior vena cava pressure, prior to and after vasopressin injection (1 IU, iv). Vasopressin caused a significant reduction in intravariceal pressure (from 22.5 +/- 9.4 to 19.2 +/- 8.4 mm Hg, p less than 0.001). Measurement of wedged hepatic venous pressure and free hepatic venous pressure closely reflected the reduction in variceal pressure. Thus, wedged hepatic venous pressure decreased by 16 +/- 11%, which is close to the 14 +/- 7% change in intravariceal pressure, and the 23 +/- 12% fall in the pressure gradient wedged hepatic venous pressure-free hepatic venous pressure was mirrored by the 26 +/- 10% change in intravariceal pressure-superior vena cava pressure. These pressure gradients decreased more than the absolute pressures (intravariceal pressure and wedged hepatic venous pressure) due to concomitant increases in superior vena cava pressure (1.9 +/- 1.9 mm Hg) and free hepatic venous pressure (0.6 +/- 1.9 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Chlorzoxazone pharmacokinetics as a marker of hepatic cytochrome P4502E1 in humans

Objective: Previous in vitro studies have demonstrated that hepatic P4502E1 metabolizes chlorzoxazone (CZX, a commonly used muscle relaxant) to 6-hydroxychlorzoxazone (6-OH-CZX). We thus assessed whether measurement of the plasma 6-OH-CZX/CZX ratio after a CZX challenge could serve as a marker of hepatic P4502E1 content.
Methods: Three subject groups were included: recently drinking alcoholics (  N = 6  ), abstinent alcoholics (  N = 5  ), and nonalcoholic subjects with liver disease (  N = 5  ) undergoing liver biopsy. Excess tissue was procured for immunochemical determination of hepatic P4502E1 content. Within an hour of the biopsy, 750 mg CZX was administered orally and serial plasma samples were collected for 6 h.
Results: Recently drinking alcoholic subjects had a higher area under the curve for plasma 6-OH-CZX (1.354 ± 0.258 μg · min · ml⁻¹) then abstinent alcoholic subjects (0.296 ± 0.080 μg · min · ml⁻¹, p < 0.005) and subjects with nonalcoholic liver disease (0.428 ± 0.061 μg · min · ml⁻¹,   p < 0.005  ). The use of the plasma 6-OH-CZX/CZX ratio at 90, 120, and 180 min discriminated between recently drinking alcoholic and nondrinking subjects. Hepatic P4502E1 content significantly correlated with the maximal 6-OH-CZX concentration (  r = 0.76  , p = 0.001) and other pharmacokinetic parameters. In the recently drinking group, the area under the curve for plasma 6-OH-CZX significantly decreased after 8 days of abstinence.
Conclusions: Measurement of plasma 6-OH-CZX after administration of a CZX challenge can serve as a marker of hepatic P4502E1 activity and thus help avoid adverse drug reactions secondary to P4502E1 induction, particularly in heavy drinkers.     

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.     

Portal hypertension in acute liver failure.

Twenty five patients with acute liver failure were measured for hepatic venous pressure gradient as an index of portal pressure during the course of a transjugular liver biopsy. Hepatic venous pressure gradient ranged from 4 to 24.5 mm Hg with a mean of 12.8 (5.3) mm Hg (normal values less than 5 mm Hg). All patients but one had increased portal pressure gradient. Portal hypertension correlated with the degree of architectural distortion of the liver, as suggested by a direct correlation between hepatic venous pressure gradient and the area of reticulin collapse, evaluated by means of a morphometric analysis on Sirius red stained liver slides (r = 0.43, p less than 0.05). Hepatic venous pressure gradient was significantly higher in patients with ascites (15.1 (5) mm Hg, n = 15) or renal failure (14.4 (5.3) mm Hg, n = 16) than in those without (9.3 (3.4) mm Hg and 10.1 (4) mm Hg, respectively; p less than 0.05). Portal hypertension was associated with systemic vasodilation and a hyperkinetic circulatory state, with decreased arterial pressure, and peripheral resistance and increased cardiac output.     

Effects of Alcohol on Intrauterine Oxygen Tension in the Rat

The effects of alcohol on the availability of oxygen within the uterine lumen of rats were determined on Day 4 of pseudopregnancy. Intraluminal oxygen tension (pO₂) was measured in vivo in anesthetized rats using a 22-gauge polarographic oxygen sensor. Intrauterine pO₂ was measured for 15 min before and after intravenous injection of alcohol (1.0 g/kg: 100% ethanol/saline, 1:2 v/v) or vehicle (physiological saline). Alcohol administration increased mean intrauterine pO₂ (mm Hg) from a pretreatment level of 28.3 ± 2.8 to 38.7 ± 3.8 mm Hg ( p < 0.05, n = 10) at 15 min postinjection. The rapid rise in oxygen tension was accompanied by increased frequency of fluctuation (peaks/hr) in intraluminal pO₂ (prealcohol: 64.2 ± 8.8 vs. postalcohol 96.0 ± 7.7 peaks/hr; ( p < 0.05, n = 10). Injection of saline did not alter any aspect of intrauterine pO₂. During the period of measurement of luminal pO₂, blood alcohol levels increased from 0 during pretreatment to 106 mg% within 10 min of injection. These results indicate that alcohol increases the availability of oxygen within the uterus during the time of endometrial sensitivity to deciduogenic stimuli and blastocyst implantation.     

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.     

Regulation of Hepatic Thrombopoietin Production by Portal Hemodynamics in Liver Cirrhosis

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 × 10⁴/μl  ;   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.     

Long-term haemodynamic effects of a 4-week regimen of nipradilol, a new beta-blocker with nitrovasodilating properties, in patients with portal hypertension due to cirrhosis. A comparative study with propranolol.

To study the long-term effects of pharmacological combination therapy, a comparison was made of the haemodynamic changes in patients with cirrhosis and portal hypertension following a 4-week treatment of propranolol or nipradilol, a new nonselective beta-blocker with nitrovasodilating effect. Nipradilol (12 mg/dag, n = 12) significantly diminished wedged hepatic venous pressure (WHVP, 25 +/- 16%), the hepatic venous pressure gradient (HVPG, 20 +/- 12%), and estimated hepatic blood flow (EHBF, 18 +/- 16%). Propranolol (30 mg/day, n = 11) also caused a significant reduction in WHVP (22 +/- 21%) and HVPG (24 +/- 21%), but not in EHBF. The percentage of portal pressure reduction and the frequency of nonresponders did not differ between the nipradilol and propranolol groups. Both agents reduced heart rate by approx. 20%. Nipradilol, however, did not cause a significant reduction in cardiac index (CI) versus a 14% reduction by propranolol. Pulmonary capillary wedge pressure and central venous pressure, an index of preload, were decreased slightly in the nipradilol group. When nonresponders were excluded, there was a significant correlation of the percentage of reduction between WHVP and CI or systemic vascular resistance, in the nipradilol group. These results indicate that nipradilol may have potent hypotensive effects on portal hypertension, similar but not superior to propranolol. Nipradilol, at the dosage used in the present study, did not appear to exert a nitrovasodilating effect to enhance the portal pressure reduction induced by beta-blocking action.     

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.