Pressure In Cirrhotic Patients Research Articles

Correlation of Internal Jugular Vein Collapsibility With Central Venous Pressure in Patients With Liver Cirrhosis.

We aimed to compare internal jugular vein and inferior vena cava ultrasonography as predictors of central venous pressure in cirrhotic patients. We performed ultrasound assessments of the internal jugular vein (IJV) and the inferior vena cava and then invasively measured central venous pressure (CVP). We then compared their correlation with CVP and performed area under the receiver operating characteristic curves to determine which had best sensitivity and specificity. IJV cross-sectional area collapsibility index at 30° correlated better with CVP ( r = -0.56, P < 0.001), and an IJV AP-CI at 30° ≤ 24.8% was better at predicting a CVP ≥8 mm Hg, with 100% sensitivity and 97.1% specificity. Thus, IJV point-of-care ultrasound might be superior than inferior vena cava point-of-care ultrasound as a predictor of CVP in cirrhotic patients.

Abstract No. 580 Correlation of Spleen Volume and Portal Pressure in Patients Undergoing TIPS

Spleen volume has been used as a predictor of adverse events in a variety of settings including assessing risk of liver failure following hepatectomy and predicting hepatocellular carcinoma (HCC) recurrence after treatment. The purpose of this study was to determine the relationship between spleen volume and portal pressure in cirrhotic patients undergoing TIPS. A review of all patients who had undergone TIPS between January 2020 and April 2022 was performed. A total of 59 patients were identified. 19 patients were excluded due to presence of portal vein thrombosis and 40 patients remained for this study. Patients were stratified based on whether they presented for emergent TIPS due to active variceal bleeding or elective TIPS for nonemergent indications. Spleen volumes were determined by semi-automated segmentation on the most recent periprocedural imaging and was divided by body surface area (BSA). Patient characteristics, MELD scores, portal pressure were evaluated. Paired t-tests were used to compare the two groups. Amongst 40 patients who underwent TIPS, 20 presented emergently and 20 presented non-emergently. MELD scores and portal pressures were significantly higher in patients presenting for emergent TIPS (P< .05), with an average MELD of 24 in the emergent TIPS group compared with 11 in the elective TIPS group and an average portal pressure of 24 in the emergent TIPS group compared with 17 in the elective TIPS group. Assessment of spleen volumes demonstrated no difference between the two groups (P = 0.25). A weak correlation of 0.38 was noted between spleen size and portal pressure (95% CI –0.08-0.70). There was no statistical difference in splenic volume between patients presenting for emergent TIPS compared with patients undergoing elective TIPS and a weak correlation between splenic volume and portal pressure. Given these findings, splenic volume may have limited prognostic value in this population. This needs to be validated in a larger population.

Effect of ET‐A blockade on portal pressure and hepatic arterial perfusion in patients with cirrhosis: A proof of concept study

AbstractBackground/aimEndothelin causes vasoconstriction via the endothelin‐A receptor (ET‐A) in the intrahepatic circulation in cirrhosis and its increase leads to portal hypertension. The aim of the study was to investigate the acute effect of a selective ET‐A antagonist in patients with portal hypertension and cirrhosis.MethodsProof‐of‐concept study with two different substudies: (a) local intrahepatic administration of the ET‐A antagonist BQ 123 and (b) systemic oral administration of the ET‐A antagonist Ambrisentan. Portal pressure was determined by hepatic venous pressure gradient (HVPG, both substudies) and hepatic arterial blood flow (HABF) by intra‐arterial Doppler measurements (substudy 1) before and under the ET‐A antagonist. Systemic haemodynamic parameters were measured in substudy 2.ResultsTwelve patients (Child‐Pugh [CP] B/C n = 7/5) were included in substudy 1 and 14 patients (CP A/B/C n = 4/6/4) in substudy 2. The relative decrease in HVPG was −12.5% (IQR: −40% to 0%; P = .05) in substudy 1 and −5.0% (IQR: −11.5% to 0%; P = .01) in substudy 2. Substudy 1 revealed higher decrease in HVPG in CP B patients. HABF increased significantly and patients without portal pressure decrease showed a higher increase of HABF. Substudy 2 showed a slight decrease in the mean arterial pressure without changes of other systemic haemodynamic parameters.ConclusionAdministration of a selective ET‐A antagonist decreases the portal pressure in cirrhotic patients. This decrease was higher in CP B patients and the non‐responders showed a higher increase in hepatic arterial flow. Selective ET‐A antagonists might be a future treatment option in patients with portal hypertension.

Partial splenic embolization is superior to intravenous somatostatin for decreasing portal pressure in cirrhotic patients: a dynamic self-controlled cohort study

Aims The efficacy of somatostatin in altering splanchnic hemodynamics in cirrhotic portal hypertension is still controversial. We aimed to establish the dynamic effect of somatostatin on portal pressure in cirrhotic patients and compared its effect with Partial Splenic Embolization (PSE). Methods Eighteen patients with cirrhotic portal hypertension were prospectively recruited. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were repeatedly measured at baseline, 1-, 5-, 10- and 20-min after initiating somatostatin infusion. After somatostatin infusion cessation and washout, WHVP and FHVP were measured before and after PSE. The change in all the variables between time points was analyzed. Results Decreased hepatic venous pressure gradient (HVPG) 5-min after initiation of infusion was identified compared with baseline level (19.6%; p-value: .042), which was achieved through elevated FHVP (37.5%; p-value: 9.26e − 04). There was no significant decrease in WHVP at any time point during somatostatin infusion. The HVPG (17.4%; p-value: 1.27e − 04) and WHVP (10.4%; p-value: 3.00e − 03) post-PSE significantly decreased compared to the washout level. No significant distribution differences in the number of patients with HVPG decrease by a percentage relative to the baseline level were identified between the 5-min time point and post-PSE. Conclusion Our study indicates that somatostatin administration does not decrease WHVP within 20 min at clinically recommended doses. While somatostatin did decrease HVPG, this effect was achieved through increased FHVP, providing a possible explanation for its unclear efficacy. In contrast, PSE decreases both the WHVP and the HVPG.

Randomised clinical study: the effects of oral taurine 6g/day vs placebo on portal hypertension.

The amino sulphonic acid taurine reduces oxidative endoplasmatic reticulum stress and inhibits hepatic stellate cell activation, which might lead to reduction of portal pressure in cirrhosis. To assess the haemodynamic effects of taurine supplementation in patients with cirrhosis and varices. Patients with hepatic venous pressure gradient (HVPG) ≥12mm Hg were included in this prospective proof of concept study. Concomitant nonselective beta-blockers therapy was not allowed. Patients received either 4weeks of oral taurine (6g/day), or placebo, prior to evaluation of HVPG response. Thirty patients were screened and 22 included in the efficacy analysis (12 taurine/10 placebo; 64% male, mean age: 52±11years, Child A: 9%, B:64%, C:27%, ascites:68%). In the taurine group, mean HVPG dropped from 20mm Hg (±4) at baseline to 18mm Hg (±4) on day 28 (mean relative change: -12%, P=.0093). In the placebo group, mean HVPG increased from 20 mm Hg (±5) at baseline to 21mm Hg (±5) on day 28 (mean relative change:+2%, P=.4945). Taurine had no significant effects on systemic haemodynamics. Seven of 12 patients (58%) on taurine achieved a HVPG response >10%, compared to none in the placebo group (P=.0053). In a multivariate linear model, HVPG reduction was significantly larger in the taurine group compared to placebo group (P=.0091 and P=.0109 for absolute and relative change respectively). Treatment-related adverse events included gastrointestinal discomfort and fatigue, and were usually mild and comparable between treatment groups. Taurine is safe and may reduce portal pressure in cirrhotic patients. More studies on the underlying mechanisms of action and long-term effects of taurine supplementation are warranted.

Endothelin 1 and transforming growth factor-β1 correlate with liver function and portal pressure in cirrhotic patients

ObjectiveThe invasive measurement of hepatic venous pressure gradient is the recommended method for the assessment of portal hypertension. We assessed if the mediators that regulate portal hypertension may be used as noninvasive markers of portal hypertension and liver insufficiency. Materials and methodsWe explored in prospective, observational study the concentration of endothelin-1, nitric oxide, and transforming growth factor-β1/2 in peripheral and hepatic venous blood; their relationship with the values of portal hypertension and liver insufficiency; and their level changes 4–6months after non-selective beta-blocker therapy in cirrhotic patients with non-bleeding esophageal varices. Results(1) Cirrhotics have significantly increased peripheral endothelin 1 and decreased transforming growth factor-β1 levels; (2) peripheral levels of all factors correlated significantly with their hepatic levels; (3) after therapy, peripheral endothelin-1 levels significantly increased, but transforming growth factor-β2 levels decreased and were lower in patients with pressure gradient value normalization; (4) before and after therapy, peripheral and hepatic endothelin-1, transforming growth factor-β1/2 levels correlated significantly with liver failure indicators (laboratory parameters, Child-Pough and MELD scores) and pressure gradient values. ConclusionsPeripheral endothelin-1 and transforming growth factor-β1 levels, which strongly correlate with their hepatic levels, reflect the stage of portal hypertension and liver insufficiency in cirrhosis.

Albumin infusion may deleteriously promote extracellular fluid overload without improving circulating hypovolemia in patients of advanced cirrhosis with diabetes mellitus and sepsis

In patients with liver cirrhosis, albumin is given to improve relative hypovolemia caused by marked splanchnic arteriolar vasodilatation. However, the volume effect of albumin is not predictable and depends also on capillary permeability, hydrostatic pressure and lymphatic ability to re-circulate albumin from interstitium to plasma. In patients with decompensated cirrhosis, the capillary permeability is increased, hydrostatic pressure is higher, and the lymphatics functions are deficient. Hence the albumin molecules are more likely to be extravasated rapidly into the interstitium and are subsequently less likely to be re-circulated back into the plasma. This would not only fail to correct circulating hypovolemia, the purpose for which it is given, but also would favor development of reverse colloid oncotic pressure and fluid movement out of the capillaries leading to development of edema. Thus, anything else which could further increase capillary permeability or hydrostatic pressure in cirrhotic patients might create more problems with albumin infusion. An increased capillary permeability is the hallmark of diabetes mellitus. Furthermore, diabetes mellitus may worsen immunodepression in cirrhotic patients thus increasing the incidence of severe infections which may further have a deleterious effect on hemodynamics and capillary permeability. A diabetic patient with advanced cirrhosis and sepsis usually has markedly increased capillary permeability, high hydrostatic pressure due to hyperdynamic circulation, and compromised lymphatic drainage capacity. Hence, using albumin infusion in them would not only fail to improve relative hypovolemia, but also would deleteriously promote extravascular accumulation of fluid, which might impair the functions of many vital organs. However, the efficacy and safety of albumin infusion in diabetic patients with advanced cirrhosis and sepsis is not known. Such data can have a great clinical implication and would necessitate search of a suitable alternative. Because albumin has relatively smaller molecular weight, synthetic colloids with a higher molecular weight might be effective in conditions of increased capillary permeability.

Intra-abdominal pressure and abdominal perfusion pressure in cirrhotic patients with septic shock.

BackgroundThe importance of intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) in cirrhotic patients with septic shock is not well studied. We evaluated the relationship between IAP and APP and outcomes of cirrhotic septic patients, and assessed the ability of these measures compared to other common resuscitative endpoints to differentiate survivors from nonsurvivors.MethodsThis study was a post hoc analysis of a randomized double-blind placebo-controlled trial in which mean arterial pressure (MAP), central venous oxygen saturation (ScvO2) and IAP were measured every 6 h in 61 cirrhotic septic patients admitted to the intensive care unit. APP was calculated as MAP - IAP. Intra-abdominal hypertension (IAH) was defined as mean IAP ≥ 12 mmHg, and abdominal hypoperfusion as mean APP < 60 mmHg. Measured outcomes included ICU and hospital mortality, need for renal replacement therapy (RRT) and ventilator- and vasopressor-free days.ResultsIAH prevalence on the first ICU day was 82%, and incidence in the first 7 days was 97%. Compared to patients with normal IAP, IAH patients had significantly higher ICU mortality (74.0% vs. 27.3%, p = 0.005), required more RRT (78.0% vs. 45.5%, p = 0.06) and had lower ventilator- and vasopressor-free days. On a multivariate logistic regression analysis, IAH was an independent predictor of both ICU mortality (odds ratio (OR), 12.20; 95% confidence interval (CI), 1.92 to 77.31, p = 0.008) and need for RRT (OR, 6.78; 95% CI, 1.29 to 35.70, p = 0.02). Using receiver operating characteristic curves, IAP (area under the curve (AUC) = 0.74, p = 0.004), APP (AUC = 0.71, p = 0.01), Acute Physiology and Chronic Health Evaluation II score (AUC = 0.71, p = 0.02), but not MAP, differentiated survivors from nonsurvivors.ConclusionsIAH is highly prevalent in cirrhotic patients with septic shock and is associated with increased ICU morbidity and mortality.

English

The aim of this study is to elucidate the effects of different dosages of octreotide on portal pressure in cirrhotic patients and to investigate the mechanism of activated human hepatic stellate cells (HSCs) on octreotide. Thirty-one (31) hepatitis B-related cirrhotic patients were randomly assigned to receive treatment with a 50 (group A, n = 12) or a 25 &micro;g/h infusion of octreotide for 72 h (group B, n = 14); the control group C (n = 5) received conventional treatment. Dynamic portal pressure was directly measured via a portal vein catheter. To study the cellular mechanism of octreotide, the expression of SSTRs 1-5 in LX-2, an HSC line, was examined by immunostaining and RT-PCR. Intracellular Ca2+&nbsp;in LX2 was measured by laser scanning confocal microscopy (LSCM). The protein and mRNA levels in all five subtypes of SSTRs were positively expressed in LX-2. Octreotide led to an immediate two-fold drop in intracellular Ca2+&nbsp;(P &lt; 0.01). Portal pressure, in both groups A and B, decreased significantly (mean, - 20.6%) after octreotide infusion. Octreotide decreased portal pressure in cirrhotic patients by inhibiting HSC contractility by decreasing intracellular Ca2+&nbsp;concentration via stimulation of all SSTRs on HSCs. &nbsp; Key words:&nbsp;Hepatic stellate cell, somatostatin receptor subtype, octreotide, portal hypertension, liver cirrhosis.

Effects of TIPS on global end-diastolic volume and cardiac output and renal resistive index in ICU patients with advanced alcoholic cirrhosis

The transjugular porto-systemic stent-shunt (TIPS) reduces portal pressure in cirrhotic patients and is used as a nonsurgical treatment for refractory ascites, recurrent variceal hemorrhage or hepatorenal syndrome. There are concerns regarding a negative impact on cirrhotic cardiomyopathy and deterioration of hyperkinetic circulatory dysfunction. We analyzed a prospectively maintained database containing hemodynamic data on cirrhotic ICU patients. Hemodynamic monitoring was performed using transpulmonary thermodilution (PiCCO, Pulsion Medical Systems, Munich, Germany). Renal perfusion was assessed by Doppler ultrasound during studies of portal and TIPS perfusion before and after the procedure. Complete data sets of 8 patients (4 male, 4 female, age 60 years (52-67), Child-Pugh-Turcotte score 10 (8-12)) were available. After TIPS, there was a substantial increase of GEDVI (646 ml/m2 (580-737) to 663 mL/m2 (643-792); p=0.036) that was even more pronounced at 24 hours (716 mL/m2 (663-821); P=0.012). CI increased from 3.3 L/min/m2 (3.1-4.2) to 3.9 L/min/m2 (3.6-5.3) (p=0.012) and 3.9 L/min/m2 (3.7-5.2) (p=0.017), respectively. There was a significant decrease of renal RI from 0.810 (0.781-0.864) to 0.746 (0.710-0.798) (p=0.028) and a transient increase of fractional excretion of sodium. SVRI (1737 dyn*s/cm5/m2 (1088 - 2115) vs. 1917 dyn*s/cm5/m2 (1368-2177) was not significantly altered immediately after TIPS but decreased to 1495 dyn*s/cm5/m2 (833-1765) at 24 hours (p=0.036)). There were no significant changes of mean arterial pressure (MAP). In conclusion, TIPS resulted in a pronounced increase of central blood volume. The observed hemodynamic effects are compatible with a preload driven increase of cardiac output and secondary decreases in SVRI and RI.

Long-term decreased portal pressure in cirrhotic patients with portal hypertension: reality or dream?

一、肝硬化门静脉高压症的自然史 门静脉高压症是指各种原因引起门静脉系统血流受阻和(或)血流量增加,导致门静脉及其属支血管内压力升高,伴侧支循环形成的一组临床综合征,包括腹水、食管胃底静脉曲张出血(EVB)、肝性脑病、肝肾综合征、肝肺综合征、门静脉高压性胃病等[1]。

The Effects of Treatment With Octreotide, Diuretics, or Both on Portal Hemodynamics in Nonazotemic Cirrhotic Patients With Ascites

To evaluate the effects of diuretic treatment, octreotide, or both on portal hemodynamics in nonazotemic cirrhotic patients with ascites. Diuretics and octreotide have been associated with a decrease in portal pressure in cirrhotic patients, suggested to be mediated by plasma volume depletion and splanchnic vasoconstriction, respectively. However, liver cirrhosis is characterized by activation of the renin-angiotensin-aldosterone axis, which increases hepatic vascular resistance and is augmented or suppressed by diuretics or octreotide, respectively. Twenty nonazotemic cirrhotic patients with ascites were treated with furosemide and spironolactone. Of them, 10 (group 1) discontinued diuretic treatment for 7 days. Thereafter for 5 days, each patient received subcutaneous octreotide, 300 microg twice per day; ten of them (group 2) received the octreotide in addition to their usual diuretic treatment. Portal and systemic hemodynamics with Doppler ultrasound and endogenous vasoactive systems were evaluated while the patients received diuretics (both groups), after discontinuation of diuretics (group 1), and after octreotide administration (both groups). The withdrawal of diuretics did not alter portal hemodynamics, but it impaired systemic hemodynamics and suppressed the renin-aldosterone axis. The addition of octreotide to diuretic treatment but not octreotide alone improved portal and systemic hemodynamics. In both groups the initiation of octreotide administration suppressed the renin-aldosterone axis and plasma glucagon levels. In nonazotemic cirrhotic patients with ascites, the combination of diuretics and octreotide improves systemic hemodynamics and inhibits the diuretic-related component of the activated renin-aldosterone axis, which in turn augments the portal hypotensive effect of diuretic-induced plasma volume depletion.

Hemodynamic effects of one week of carvedilol administration on cirrhotic rats

Carvedilol is a nonselective beta-blocker with alpha(1)-adrenergic blocking activity. It has been shown to decrease portal pressure in cirrhotic patients. The current study was undertaken to evaluate the possible mechanism of carvedilol on hemodynamics in cirrhotic rats with portal hypertension produced by common bile duct ligation. Male Sprague-Dawley rats received either a sham operation or common bile duct ligation. Three weeks after surgery, both sham-operated and cirrhotic rats were randomly assigned to receive vehicle or carvedilol 5 mg.kg(-1).12 h(-1) by gastric gavage for 1 week. Hemodynamic measurements, serum biochemistry, serum nitrate/nitrite and 6-keto-PGF(1alpha) levels, and aortic mRNA expression of eNOS and COX-1 were performed on the eighth day after drug administration. Carvedilol treatment did not affect serum biochemistry in either sham-operated or cirrhotic rats. In sham-operated rats, administration of carvedilol significantly decreased the heart rate without affecting other hemodynamic values. In contrast, in cirrhotic rats, administration of carvedilol significantly decreased the cardiac index, portal pressure, heart rate, and portal territory blood flow, and it significantly increased systemic and portal territory vascular resistances. The hepatocollateral resistance was significantly decreased, but the hepatic arterial blood showed no significant changes. In sham-operated rats treated with carvedilol, serum nitrate/nitrite and 6-keto-PGF(1alpha) levels were not affected. In contrast, cirrhotic rats receiving carvedilol showed a significant decrease in serum nitrate/nitrite and 6-keto-PGF(1alpha) levels, associated with a decrease in aortic mRNA expression of eNOS and COX-1 compared with those receiving vehicle. Carvedilol decreased portal pressure through a reduction of splanchnic blood flow associated with a decrease in hepatocollateral resistance. Additionally, administration of carvedilol decreased endothelial-related vasodilatory activities.

Assessment of the agreement between wedge hepatic vein pressure and portal vein pressure in cirrhotic patients

Background. Measuring wedged hepatic venous pressure and hepatic venous pressure gradient as indices of portal pressure is being increasingly used in assessing the prognosis and response to pharmacological treatment for portal hypertension in cirrhotic patients. Aim. To re-evaluate the agreement and correlation between wedged hepatic pressures and directly measured portal pressures. Methods. Medline search for studies comparing direct portal with wedged hepatic pressure measurement and assessment of correlation and agreement of the pooled data. Results. Eleven suitable studies included 320 patients. Coefficient of determination ( r 2) was 0.87 in all patients, 0.87 in 102 patients with alcoholic liver disease, 0.83 in 88 patients with non-alcoholic liver disease and 0.75 in 53 patients with hepatitis C-related liver disease. Coefficient of determination was 0.85 in the 194 patients in whom a wedge catheter and 0.90 in the 113 patients in whom a balloon catheter was used. Agreement according to the method of Bland and Altman was also found to be good, with only 4–8% of the measurements outside 2 standard deviations. Conclusions. Wedged hepatic pressure measurement correlates well with direct portal pressure measurement and the agreement is sufficiently good to use this as a surrogate measurement.

196 Renovascular impedance correlates with portal pressure in cirrhotic patients

196 Renovascular impedance correlates with portal pressure in cirrhotic patients

Trial for treatment of refractory ascites TIPS the scales

Trial for treatment of refractory ascites TIPS the scales

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.

Captoril reduced portal pressure in cirrhotic patients with low portal venous velocity

Captoril reduced portal pressure in cirrhotic patients with low portal venous velocity

Effects of long-term Irbesartan in reducing portal pressure in cirrhotic patients: comparison with propranolol in a randomised controlled study

Background/Aims: The role of angiotensin II (AT-II) type I receptor antagonists in the treatment of portal hypertension remains controversial. We tested the efficacy of Irbesartan (Irb) vs. Propranolol (Pro) in reducing portal pressure and evaluated its systemic haemodynamic effects. Methods: Thirty-four patients were randomly assigned to receive either Irb 300 mg/day (19 patients) or Pro 40–120 mg/day (15 patients) for 2 months. Results: Irb was discontinued in five patients (26%). No major side effect occurred in the Pro group. On an average, the portal pressure gradient decreased significantly more in the Pro than in the Irb group (median −19.5%, range −11/−31% vs. −4.8%, +2.5/−10%, P<0.001). A clinically significant decrease was seen in one (7%) of the patients given Irb vs. five (33%) given Pro ( P<0.02). The fall in mean arterial pressure was significantly higher with Irb than with Pro (median −29%, range −15/−45% vs. −4.9%, +8/−19%, P<0.02). Irb significantly modified the blood creatinine clearance (median −29 ml/m, range +9/−61 ml/m, −30, −24/−35% P<0.0001 vs. basal). Conclusions: Irb offers no advantage over Pro in the control of portal hypertension. Moreover, its therapeutic profile is limited by important side effects.

Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers

Nitroglycerin (NTG), a nitric oxide (NO) donor, has been shown to reduce portal pressure in cirrhotic patients. Using the in situ perfusion of normal and cirrhotic rat livers, we compared the vascular relaxation induced by either NTG or the spontaneous nitric oxide donor S-nitroso- N-acetylpenicillamine (SNAP). Normal and cirrhotic livers were perfused (40 mL/min, 37°C) with Krebs' solution in a recirculating system. After preconstriction with methoxamine (10 −4 mol/L), a dose-response study was performed using 6 cumulative doses of NTG or SNAP (10 −7 to 3 × 10 −5 mol/L). NO x (NO 2 − + NO[overthree]) production in the perfusate was measured by chemiluminescence. Cirrhotic livers exhibited lower vasorelaxant responses, compared with normal livers, to both NTG ( P < .0001) and SNAP ( P = .0020). In normal livers, NTG and SNAP induced similar vasorelaxant responses ( P = .44). In cirrhotic livers, NTG induced less vasorelaxation than SNAP ( P < .0001). In the presence of NTG ( P = .0045), but not SNAP ( P = .99), NO x production in experiments with cirrhotic livers was lower than in experiments with normal livers. In conclusion, in cirrhotic rat livers, the vasorelaxant response to NTG is impaired owing to both a decreased metabolism of this NO donor and an inability of the hepatic vasculature to respond to NO. (H EPATOLOGY 2002;36:381-385.)