Endoscopic Assessment of Variceal Volume and Wall Tension in Cirrhotic Patients: Effects of Pharmacological Therapy

Transcription

1 GASTROENTEROLOGY 1997;113: Endoscopic Assessment of Variceal Volume and Wall Tension in Cirrhotic Patients: Effects of Pharmacological Therapy ÀNGELS ESCORSELL,* JOSEP M. BORDAS, FAUST FEU,* JOAN CARLES GARCÍA PAGÁN,* ÀNGELS GINÈS, JAUME BOSCH,* and JOAN RODÉS* *Liver Unit and Endoscopy Unit, Hospital Clinic, Department of Medicine, University of Barcelona, Barcelona, Spain Background & Aims: Variceal rupture is believed to oc- variceal wall tension is determined by transmural prescur when variceal wall tension is excessive. The com- sure (the difference between intravariceal and esophageal bined use of endosonography, allowing the objective luminal pressures) times the radius of the varix, divided measurement of variceal radius, and endoscopic mea- by the thickness of the variceal wall. 1 Although transmusurement of transmural variceal pressure may enable ral variceal pressure can be measured using several methassessment of this important parameter. The aim of ods, 3 5 wall tension has been an elusive parameter bethis study was to assess the effects on variceal hemocause of the lack of objective methods to accurately dynamics of drugs acting through different mechameasure variceal radius and wall thickness. The introducnisms: decreasing portocollateral blood flow (propranotion of endosonography, by obtaining cross-sectional lol) or resistance (isosorbide-5-mononitrate [ISMN]). Methods: Repeated measurements of variceal radius, images of the esophagus, has opened new prospects in the volume (by endosonography), and transmural pressure evaluation of esophageal varices, 6 9 including objective (using endoscopic gauge) were performed in 27 cirrhotic measurements of variceal radius. 7,8 The combined use of patients at baseline and 40 minutes after double- endosonography and endoscopic measurement of trans- blind administration of placebo (n Å 9), propranolol (n mural variceal pressure allows a quantitative approach to Å 9), orismn(nå9). Results: Placebo had no effect. variceal wall tension measurement. Propranolol significantly reduced variceal volume The present study used this combined approach to (032% { 26%; P Å 0.01), radius (012% { 9%; P õ assess variceal wall tension in baseline conditions and 0.005), and pressure (026% { 10%; P õ ). The after short-term double-blind administration of vasoresulting decrease in wall tension (034% { 13%; P õ active drugs that decrease portal pressure through differ ) exceeded that in transmural pressure (P õ ent mechanisms: by reducing portocollateral blood flow 0.01). ISMN reduced transmural variceal pressure (026% { 21%; P õ 0.005), but not radius (03% { (propranolol) 10,11 or by decreasing portocollateral resis- 14%; NS) and volume (09% { 31%; NS). Conclusions: tance (isosorbide-5-mononitrate [ISMN]). 12,13 The combination of endosonography and endoscopic measurement of transmural variceal pressure allows Materials and Methods quantitative estimation of variceal wall tension. Proand The study was performed in 27 patients with cirrhosis pranolol and ISMN reduce similarly transmural variceal esophageal varices referred to the Hepatic Hemodynamic pressure. Propranolol, but not ISMN, reduces variceal Laboratory for evaluation of pharmacotherapy for portal hyper- volume and radius. Therefore, despite similar decreases tension. Twenty patients were male and 7 female; the mean age in variceal wall tension, propranolol may offer a greater was 59 { 9 years (mean { SD; range, years). Nine had therapeutic effect than ISMN in portal hypertension. previously bled from esophageal varices, as shown by emergency endoscopy during acute bleeding, and 17 patients had not. There was 1 nonassessable patient (with a history of an episode of dark emorrhage from gastroesophageal varices is the stools that was not investigated). Cirrhosis was alcoholic in 13 H patients and posthepatitic in 14. Additional clinical data are pathophysiology of variceal hemorrhage is still not com- shown in Table 1. The study was approved by the Ethical pletely understood. Increasing evidence supports that the Research Committee in All patients gave their written main factor leading to variceal rupture is the tension informed consent to participate in the study. exerted over the thin variceal wall. 1,2 Variceal wall tenvariceal pressure and endosonography were performed after Upper gastrointestinal endoscopy to measure transmural sion is the inwardly directed force that opposes the expanding force exerted on the variceal wall by the in- Abbreviation used in this paper: ISMN, isosorbide-5-mononitrate. creased intravascular pressure and blood flow by the American Gastroenterological Association According to Frank s modification of the Laplace s law, /97/$3.00

2 November 1997 VARICEAL HEMODYNAMICS IN CIRRHOSIS 1641 Table 1. Baseline Clinical, Endoscopic, and Hemodynamic Data of Cirrhotic Patients Characteristics Placebo (n Å 9) Propranolol (n Å 9) ISMN (n Å 9) Age (yr) a 61 { { { 7 Sex (M/F) 7/2 7/2 6/3 Pathogenesis of cirrhosis Alcoholic Nonalcoholic Child Pugh score a 7.8 { { { 0.9 b Ascites (yes/no) 5/4 5/4 1/8 Previous variceal bleeding (yes/no) 3/5 (1 NA) 4/4 (1 NA) 2/5 (2 NA) Estimated diameter of varices (mm) a 6.2 { { { 2 Diameter of varices at EUS (mm) a 7.1 { { { 1.7 NIEC index a 28 { 3 31 { 8 27 { 4 Heart rate (bpm) a 86 { { { 14 Mean arterial pressure (mm Hg) a 78 { { 7 86 { 14 Variceal pressure (mm Hg) a 14.6 { { { 3.5 Variceal volume (mm 3 ) a 1406 { { { 660 Tension of variceal wall (mg/mm) a 685 { { { 164 EUS, endoscopic ultrasonography; NIEC, North Italian Endoscopic Club; NA, nonassessable. a Data expressed as mean { SD. b P õ 0.05 vs. other groups. an overnight fast under slight sedation with intravenous (IV) graphic pictures (n Å 2), or withdrawal of consent to continue midazolam (0.1 mg/kg). 13 Heart rate, mean arterial pressure, the study (n Å 1). and arterial saturation of oxygen were measured noninvasively The analysis of transmural variceal pressure tracings and throughout the study (Cardioswiss CM-8; Schiller AG, Baar, endosonographic images was performed under blind condi- Switzerland). After a detailed examination of the varices (in- tions. The randomization code was not opened until all studies cluding estimation of variceal size, presence of red color signs, had been completed and analyzed. and number of variceal columns), transmural variceal pressure Measurement of Esophageal Transmural was measured at the largest varix, in the distal 5 cm of the esophagus. 2,10,13,14 The procedures are detailed below. After Variceal Pressure successful pressure measurements, the fiberscope (Olympus Esophageal transmural variceal pressure was assessed GIF-Q20; Olympus Optical Co., Tokyo, Japan) was removed with a previously described noninvasive technique using a minand replaced by an echoendoscope (Olympus GF-UM2) that iature pressure-sensitive capsule (measuring surface, 2 mm in was advanced up to the gastroesophageal junction. Then five diameter, Varipress; Labotron, Barcelona, Spain) attached to a series of three frozen images were obtained at each 1-cm inter- fiberscope tip. 10,13,14 val from the gastroesophageal junction to 4 cm above. This Transmural variceal pressure was expressed as the difference point is relevant considering that our study focused on the between the pressure inside the varix and the intraesophageal distal esophagus; this is the most frequent site of variceal pressure (measured through an additional channel attached to rupture because, in this area, variceal veins run superficially, the endoscope s external surface). Before each study, the pressure-sensitive through the subepithelial layers of the lamina propria. 15 capsule was calibrated with an artificial varix After completing these measurements, the patients were system. 2 Previous studies have shown the accuracy and reproducibility randomly allocated to receive either propranolol (0.15 mg/kg of the technique. 2,3,10,13,14 IV) plus a tablet of placebo (n Å 9); placebo (isotonic saline) The same investigator performed all measurements under IV plus a tablet of ISMN (40 mg; n Å 9); or IV placebo plus blind conditions. He was unaware of the results that were a placebo tablet (n Å 9). The randomization code was generated being recorded; he was only told, by another member of the by computer. Endosonography and transmural variceal pressure team, if the pressure tracings were satisfactory (stable intra- measurement were started again 40 minutes later. This time esophageal pressure, absence of artifacts, and correct placement period was chosen on the basis of previous studies showing that of the capsule over the varix for at least 12 seconds) or not. A the maximum effect of ISMN on the hepatic venous pressure minimum of three satisfactory measurements were required at gradient was achieved minutes after its oral administration. each period of the study. Transmural variceal pressure was 12 Both propranolol and ISMN have also been shown to taken as the mean of the satisfactory measurements obtained. significantly reduce transmural variceal pressure 20 and 40 Measurement of Radius and Volume of minutes after similar dosage administration. 10,13,14 Thirty-four patients were initially enrolled, but 7 were not included in Varices the analysis because of lack of satisfactory baseline or repeated A radial echoendoscope scannning 360 and oriented transmural variceal pressure measurements (n Å 4), endosono- perpendicular to the long axis of the insertion tube was used.

3 1642 ESCORSELL ET AL. GASTROENTEROLOGY Vol. 113, No. 5 Although both 7.5- and 12-MHz frequencies were available, the studies were performed using 12 MHz to improve image resolution and delineation of the varices within the esophageal wall. A water-filled balloon placed at the distal end of the instrument was used to create a water interface between the transducer and the esophageal wall. The balloon was filled under very low pressure to obtain satisfactory images without compressing the intramural varices. The pressure of the waterfilled balloon was kept õ5 mm Hg in all cases, as measured by the pressure-sensitive capsule used in the transmural variceal pressure measurement. The five series of endosonographic cross-sectional images obtained at 1-cm intervals from the gastroesophageal junction were recorded by a multi-imager camera (Minisys Video Imager PS2; Barcelona, Spain), and then submitted to a blind morphometric analysis using an automatic computerized image analysis system (Olympus CUE-2, version 4.0; Olympus Optical Co.). Esophageal varices were identified as roundish, echo-free structures, located mostly in the submucosal layer (Figure 1). 16 After selecting the bigger varix, its borders were traced with a computer-connected mouse (Figure 1). Then, the computerized system automatically calculated the crosssectional area of the varix (square millimeters) and the equivalent diameter. The mean of the measurements from the three images obtained at each 1-cm interval was taken as the variceal diameter. The average of the diameters measured at each 1- cm interval was used in the variceal wall tension calculation. Variceal volume was calculated from the three-dimensional reconstruction of a 4-cm variceal column (Figure 2), assuming that the variceal column can be described as the sum of four segments shaped as a semitruncated conus of 1-cm height. The volume (V) of each 1-cm variceal segment (i) was calculated as follows: V i (mm 3 ) Å (Cross-sectional Area a / Cross-sectional Area b ) (mm 2 ) 1 Height (10 mm)/2. The volume of the 4-cm variceal column was calculated by adding the volume of each segment (Figure 2). correction for multiple comparisons. Correlation among vari- ables was performed using the Pearson s correlation coefficient. Significance was established at P õ Calculation of Variceal Wall Tension Variceal wall tension was estimated as the product of the transmural variceal pressure times the mean radius of the varix as follows: Wall Tension (mgrmm 01 ) Å Transmural Variceal Pressure (mgrmm 02 ) 1 Variceal Radius (mm). (Conversion factor for pressure measurements: 1 mm Hg Å mgrmm 02.) The variceal wall thickness was not included in the calculation because it cannot be measured accurately enough, and it is unlikely to be significantly modified by drugs. Data Analysis The results are reported as mean { SD. Only the varices that could be identified at baseline and after drug adminis- tration were considered for statistical analysis. The effects of active drug or placebo administration were evaluated using Student s t test for paired data within each group. Comparison among groups was performed by analysis of variance test followed by Student s t test for unpaired data with Bonferroni Figure 1. (A) Cross-sectional image of distal esophagus. (B) Scheme from the same image with the borders of the bigger varix outlined to compute its cross-sectional area and diameter. Asterisk indicates an esophageal varix. Results Baseline Data Baseline clinical and endoscopic data of the pa- tients are shown in Table 1. The three groups of patients were comparable in baseline demographic, clinical, endoscopic, and hemodynamic parameters, except for the Child Pugh score, which was similar in patients receiving propranolol and placebo but slightly higher than that of those receiving ISMN (Table 1). All patients had large esophageal varices. There was a significant but weak correlation between variceal size estimated through compar- ison with the size of the pressure gauge during endoscopy

4 November 1997 VARICEAL HEMODYNAMICS IN CIRRHOSIS 1643 P õ 0.05) but not mean arterial pressure (2% { 5%; NS) (Table 2). In contrast, administration of 40 mg of ISMN significantly reduced mean arterial pressure (020% { 8%; P õ ), whereas heart rate was not significantly modified (4% { 11%; NS) (Table 2). Transmural variceal pressure. Propranolol and ISMN caused a significant and similar decrease in transmural variceal pressure (propranolol, 026% { 10%; P õ ; ISMN, 026% { 21%; P õ 0.005; NS between them) (Table 2). Individual changes are shown in Figure 3. Radius and volume of esophageal varices. Propranolol caused a significant reduction of variceal radius Figure 2. Schematic representation of the three-dimensional reconstruction of a variceal column from fiv cross-sectional endosono- (011.6% { 9.2%; P õ 0.005) and volume (031.8% graphic images obtained at 10-mm intervals. The variceal area was { 26.47%; P Å 0.01). These changes were observed in calculated by planimetry at each section (A 1 to A 5 ). Variceal volume (V varix ) was calculated as the sum of the volume of four variceal segsignificant effects on the radius and volume of esophageal every patient (Figure 4). On the contrary, ISMN had no ments (V a to V d ). varices (mean changes, 02.9% { 7.6% and 09.2% { 31%, respectively; NS). The individual responses were and that measured by endosonography (r Å 0.57; P õ highly heterogeneous (Figure 4). The effects of proprano- 0.02). The level of intraobserver agreement for repeated lol were different from those of ISMN (P õ 0.05 for measurements of variceal radius and volume of the varices variceal radius; P Å 0.1 for variceal volume) and placebo was excellent (r Å 0.89, P õ 0.01; and r Å 0.96, P õ (P õ 0.02 for both variceal radius and volume) (Table 0.001, respectively). In this selected series of patients 2 and Figure 4). with large varices, there were no differences in variceal Variceal wall tension. As a result of the reduction radius and volume between bleeders and nonbleeders (rareceiving in transmural variceal pressure and radius, all patients dius, 3.3 { 0.8 vs. 3.6 { 1.0 mm; volume, 1684 { 985 propranolol experienced a marked decrease in vs { 661 mm 3 ; NS). Those with previous bleeding variceal wall tension (034% { 13%; P õ ) (Table from esophageal varices had higher variceal pressure (17.1 2). Decrease of wall tension after propranolol administra- { 4 vs { 2.7 mm Hg; P Å 0.05) and variceal tion was significantly greater than the decrease of wall tension (379 { 116 vs. 286 { 42 mg/mm; P õ transmural variceal pressure (026% { 10%; P õ 0.005). 0.05) than those without. Variceal bleeders also had ISMN also caused a significant decrease of variceal wall higher Child Pugh score (8 { 2.2 vs. 6.4 { 1.4; P Å tension (028% { 20%). However, because of its lack 0.05) and North Italian Endoscopic Club index (31 { of effects on radius, wall tension decrease was not greater 5 vs. 26 { 4; P õ 0.01). than the decrease in transmural pressure (026% { 21%; Effects of Placebo Administration NS). Results are shown in Figure 5. Placebo administration had no significant effects. Discussion As shown in Table 2, neither heart rate, mean arterial Variceal bleeding is believed to occur when the pressure, transmural variceal pressure, radius and volume tension exerted over the thin wall of the varices increases of the varices, nor the tension of variceal wall were sig- beyond a critical value determined by the elastic limit nificantly modified. Importantly, very little variation was of the vessel. 1 Transmural variceal pressure and size are observed on these measurements (00.8% { 9% for key factors determining variceal wall tension. 1,3,8 Thus, transmural variceal pressure, 01.5% { 7.7% for variceal its measurement may offer a better assessment of bleeding radius, 4.5% { 19% for variceal volume, and 02.2% risk and of the effects of pharmacotherapy of portal hyper- { 12.7% for wall tension; NS). Individual data are shown tension than other hemodynamic parameters. The noninin Figures 3 and 4. vasive endoscopic technique used to measure the transmural pressure of the varices is accurate, reproduc- Effects of Propranolol or ISMN ible, and adequate to assess the effects of drug ther- Administration apy, 10,13,14 as confirmed in the present study by lack of Systemic hemodynamics. Propranolol significantly changes and little variability after placebo administrabe reduced heart rate (mean change, 019% { 10%; tion. Until recently, esophageal variceal size could

5 1644 ESCORSELL ET AL. GASTROENTEROLOGY Vol. 113, No. 5 Table 2. Changes in Systemic Hemodynamics and Pressure, Volume, Radius, and Wall Tension of Esophageal Varices After Double-Blind Administration of Placebo, Propranolol, and ISMN Placebo (n Å 9) Propranolol (n Å 9) ISMN (n Å 9) Baseline 40 min Baseline 40 min Baseline 40 min Mean arterial pressure (mm Hg) 78 { { { 7 80 { 7 86 { { 13 a,b Heart rate (bpm) 86 { { { { 12 a,b 91 { { 15 Variceal pressure (mm Hg) 14.6 { { { { 2.6 a,b 13.9 { { 4.1 a,b Variceal volume (mm 3 ) 1406 { { { { 660 a 1645 { { 585 Variceal radius (mm) 3.6 { { { { 0.7 a,b 3.5 { { 0.7 Variceal wall tension (mg/mm) 685 { { { { 182 a,b 649 { { 138 a,b NOTE. Data are expressed as mean { SD. a P õ 0.01 vs. baseline. b P õ 0.05 vs. placebo. only estimated from the comparison with objects of a cess rate. However, the advent of high-resolution endoluminal known size, such as the pressure-sensitive endoscopic sonography catheters, such as the prototype used gauge or opened biopsy forceps. This precluded reliable by Miller et al., 8,9 may facilitate obtaining satisfactory calculations of variceal wall tension, which is probably images even in patients with small varices. the most relevant parameter. Endosonography is an increasingly available technique As confirmed by this study, endosonography overcomes because of its multiple applications in gastroenterology. this problem by obtaining transversal pictures of The combination of measurements of variceal radius and the esophagus where the radius of the varices can be transmural pressure allows a quantitative approach to quantitatively measured with a computer-aided morpho- the measurement of wall tension and represents a new metric analysis. 7 9 These measurements were highly reproducible, technique for the evaluation of variceal hemodynamics in as shown by the low variability (õ5%) of portal-hypertensive patients. Moreover, endosonography repeated measurements obtained before and after the allowed the calculation of variceal volume on a three- double-blind administration of placebo and by the highly dimensional reconstruction based on serial cross-sectional significant intraobserver agreement. images. The measurement of changes in variceal volume The endosonographic equipment used required a wa- can provide useful information on the hemodynamic ter-filled balloon to create a water interface between the changes at the varices. This measurement, contrary to transducer and the esophageal wall. To minimize the that of wall tension, does not require separate determination artifacts that this may cause, the balloon was filled under of transmural variceal pressure. very low pressure, õ5 mm Hg in all cases, which is This study confirms our previous results showing that much less than the transmural variceal pressure observed propranolol and ISMN achieve marked, but similar, de- in our patients (range, mm Hg). Using these creases in transmural variceal pressure. 10,13,14 The results precautions, satisfactory images were obtained in 32 of also show that propranolol significantly reduces the vol- 34 patients. The fact that we selected patients with large ume and the radius of the varices. This change is not varices may have contributed to the high technical suc- unexpected because propranolol, in addition to decreas- Figure 3. Individual values of transmural pressure of esophageal varices after short-term double-blind administration of (A) placebo, (B) propranolol, or (C ) ISMN.

6 November 1997 VARICEAL HEMODYNAMICS IN CIRRHOSIS 1645 Figure 4. Individual values of variceal volume after short-term double-blind administration of (A) placebo, (B) propranolol, or (C ) ISMN. ing portal pressure, consistently and markedly reduces the decline in portal or transmural variceal pressure. The azygos blood flow, 10,11,17 which is an index of the blood reduction in wall tension caused by ISMN was not greater flow through gastroesophageal collaterals and varices. 18 than that observed in transmural variceal pressure. Therefore, Interestingly, ISMN did not significantly reduce the variceal despite similar decreases in transmural variceal pres- radius and volume, which agrees with its variable sure, propranolol is likely to afford a greater protection effects on azygos blood flow. 12,13,19 21 These findings suggest from bleeding risk than ISMN because of its added effects that endosonographic measurements of the changes on variceal size. in variceal radius and volume after the administration An effective protection from bleeding risk requires of splanchnic vasoconstrictors, such as propranolol, may propranolol to decrease portal pressure by more than 20% represent a new noninvasive and objective way of as- of baseline, which is achieved in only one third of the sessing its beneficial effects. However, our results also patients. 22 In light of the results of this study, obtaining indicate that this method is not adequate to assess the effective protection from an agent such as ISMN, which effects of vasodilators, which may reduce transmural vari- decreases portal pressure but does not influence collateral ceal pressure despite the lack of changes in endosono- blood flow and variceal radius, will require a greater graphic parameters. pressure reduction. By reducing transmural variceal pressure and size, pro- In summary, our results show that propranolol and pranolol caused a marked decrease of variceal wall ten- ISMN caused marked and similar reductions in transmusion, which significantly exceeded its effects on transmu- ral variceal pressure. However, propranolol, not ISMN, ral variceal pressure. This finding suggests that the reduced variceal volume and radius. As a consequence beneficial effects of propranolol in reducing the risk of propranolol, not ISMN, achieved a greater decrease in variceal bleeding exceed what should be anticipated from wall tension than in transmural variceal pressure. For an equal decrease in portal or transmural variceal pressure, propranolol may offer a greater therapeutic benefit than ISMN in portal hypertension. References 1. Polio J, Groszmann RJ. Hemodynamic factors involved in the development and rupture of esophageal varices: a pathophysiologic approach to treatment. Semin Liver Dis 1986; 6: Rigau J, Bosch J, Bordas JM, Navasa M, Mastai R, Kravetz D, Bruix J, Feu F, Rodés J. Endoscopic measurement of variceal pressure in cirrhosis: correlation with portal pressure and variceal hemorrhage. Gastroenterology 1989; 96: Bosch J, Bordas JM, Rigau J, Viola C, Mastai R, Kravetz D, Navasa M, Rodés J. Noninvasive measurement of the pressure of esophageal varices using an endoscopic gauge: comparison with measurements by variceal puncture in patients undergoing endoscopic sclerotherapy. Hepatology 1986; 6: Figure 5. Effects of short-term administration of placebo, propranolol, or ISMN on variceal pressure ( ), radius ( ), and wall tension ( ) 4. Mosimann R. Non-aggressive assessment of portal hypertension expressed as percent change from baseline values.* P õ 0.05 vs. using endoscopic measurement of variceal pressure. Preliminary baseline and placebo. report. Am J Surg 1982; 143:

7 1646 ESCORSELL ET AL. GASTROENTEROLOGY Vol. 113, No Staritz M, Meyer zum Buschenfelde KH. The endoscopic mea- 16. Aibe T, Fuji T, Okita K, Takemoto T. A fundamental study of surement of intravascular pressure and flo in esophageal varices. normal layer structure of the gastrointestinal wall visualized by J Hepatol 1988; 7: endoscopic ultrasonography. Scand J Gastroenterol 1986; 21: 6. Caletti GC, Brocchi E, Baraldini M, Ferravi A, Gibilaro M, Barbara L. Assessment of portal hypertension by endoscopic ultrasonog- 17. Kroeger RJ, Groszmann RJ. Effect of selective blockade of betaraphy. Gastrointest Endosc 1990; 36:S21 S27. 2-adrenergic receptors on portal and systemic hemodynamics in 7. Liu JB, Miller LS, Feld RI, Barbarevech CA, Needleman L, Gold- a portal hypertensive rat model. Gastroenterology 1985; 88: berg BB. Gastric and esophageal varices: 20-MHz transnasal endoluminal US. Radiology 1993; 187: Bosch J, Groszmann RJ. Measurement of the azygos venous 8. Miller LS, Schiano T, Liu JB, Baranowski R, Bellary S, Black M. blood flo by a continuous thermal dilution technique. An index Use of high resolution endoluminal sonography to measure vari- of blood flo through gastroesophageal collaterals in cirrhosis. ables (wall thickness and radius) involved in the calculation of Hepatology 1984; 4: variceal wall tension by the Laplace equation (abstr). Gastroen- 19. Blei AT, GarcıBa-Tsao G, Groszmann RJ, Kahrilas P, Ganger D, terology 1995; 108:A1123. Morse S, Fung HL. Hemodynamic evaluation of isosorbide dini- 9. Miller LS, Schiano TD, Adrain A, Cassidy M, Liu JB, Ter H, Bellary trate in alcoholic cirrhosis. Gastroenterology 1987; 93:576 SV, Dabezies MA, Black M. Comparison of high-resolution endoluminal 583. sonography to video endoscopy in the detection and evalu- 20. Grose RD, Plevris JN, Redhead DN, Bouchier IAD, Hayes P. The ation of esophageal varices. Hepatology 1996; 24: acute and chronic effects of isosorbide-5-mononitrate on portal 10. Feu F, Bordas JM, Luca A, GarcıBa-PagaB n JC, Escorsell A, Bosch hemodynamics in cirrhosis. J Hepatol 1994; 20: J, Rodés J. Reduction of variceal pressure by propranolol: comparison 21. GarcıBa-Tsao G, Groszmann RJ. Portal hemodynamics during nitroin of the effects on portal pressure and azygos blood flo glycerin administration in cirrhotic patients. Hepatology 1987; 7: patients with cirrhosis. Hepatology 1993; 18: Bosch J, Mastai R, Kravetz D, Bruix J, Gaya J, Rigau J, Rodés J. 22. Feu F, GarcıBa-PagaB n JC, Bosch J, Luca A, Terés J, Escorsell A, Effects of propranolol on azygos blood flo and hepatic and systemic Rodés J. Relation between portal pressure response to pharma- hemodynamics in cirrhosis. Hepatology 1984; 4:1200 cotherapy and risk of recurrent variceal hemorrhage in patients with cirrhosis. Lancet 1995; 346: Navasa M, Chesta J, Bosch J, Rodés J. Reduction of portal pressure by isosorbide-5-mononitrate in patients with cirrhosis. Gastroenterology 1989; 96: Received January 23, Accepted July 11, Escorsell A, Feu F, Bordas JM, GarcıBa-PagaB n JC, Luca A, Bosch Address requests for reprints to: Jaume Bosch, M.D., Hepatic He- J, Rodés J. Effects of isosorbide-5-mononitrate on variceal pres- modynamic Laboratory, Liver Unit, Hospital ClıB nic i Provincial, Villarroel sure and systemic and splanchnic hemodynamics in patients 170, Barcelona, Spain. with cirrhosis. J Hepatol 1996; 24: Supported in part by grants 94/0757 and 97/1309 from the Fondo 14. Feu F, Bordas JM, GarcıBa-PagaB n JC, Bosch J, Rodés J. Doubleblind de Investigación de la Seguridad Social and by PB 94/1562 from investigation of the effects of propranolol and placebo on Dirección General de Investigación Científica y Technológica. Dr. Es- the pressure of esophageal varices in patients with portal hypertension. corsell was a recipient of a fellowship award (FI/ ) by the Hepatology 1991; 13: Generalitat de Catalunya. 15. Noda T. Angioarchitectural study of esophageal varices. With The authors thank Angels Baringo, Laura Rocabert, and the nursing special reference to variceal rupture. Virchows Arch (Pathol Anat) staff of the Endoscopy Unit for their expert assistance and Diana 1984; 404: Bird for secretarial support.