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We have evaluated gastric mucus generation (study 1) and the effects of tetraprenylacetone on gastric mucus generation (study 2) in cirrhotic patients with portal hypertension. Study 1: Included were 50 noncirrhotics (group A), 25 cirrhotics without portal hypertension (group B), and 25 cirrhotics with portal hypertension (group C). The antrum, corpus, and fundus mucus generation was assessed by hexosamine concentration using biopsy specimens. In groups A and B, the antrum hexosamine concentration was significantly higher compared with the corpus (P < 0.01, P < 0.01) and the fundus (P < 0.01). In contrast, the hexosamine concentration at each location was similar in group C. Furthermore, the antrum hexosamine concentration of group C was significantly lower compared with that of group A (P < 0.05). In study 2, a double-blind design, 300 mg of tetraprenylacetone was administered for four weeks in 10 cirrhotics with portal hypertension and placebo in 10. The regional hexosamine concentrations were measured before and after drug administration. Placebo administration did not change hexosamine concentration at each location. In contrast, tetraprenylacetone increased the antrum and corpus hexosamine concentration (P < 0.01, P < 0.05), although the fundus concentration did not change. These data suggest that cirrhotics with portal hypertension have reduced gastric antral mucus generation and tetraprenylacetone normalizes this.

The effects of vasopressin plus oxygen and vasopressin alone on gastric mucosal perfusion and oxygenation were studied using reflectance spectrophotometry and laser Doppler velocimetry in 23 cirrhotic patients with portal-hypertensive gastropathy. The measurements were performed under basal conditions and after double-blinded administration of placebo (n = 7), vasopressin (0.3 U/min; n = 8) or vasopressin (0.3 U/min) plus nasal oxygen (4 L/min; n = 8). No significant effects on gastric mucosal haemodynamics and oxygenation were observed after placebo. In contrast, vasopressin and vasopressin plus oxygen induced a similar reduction in haemoglobin content (-26 +/- 2 and -21 +/- 4%, respectively P < 0.01), and laser Doppler signal (-23 +/- 2 and -22 +/- 2%, respectively, P < 0.01). Although each treatment induced a significant reduction in oxygen saturation (-21 +/- 2 and -7 +/- 1%, respectively P < 0.01), the effect was less pronounced in patients receiving the combination than in those receiving vasopressin alone (P < 0.01). These data suggest that vasopressin and vasopressin plus oxygen reduce gastric mucosal hyperaemia and that the oxygen supplement partially protects against gastric mucosal hypoxia during vasopressin infusion in cirrhotic patients with portal-hypertensive gastropathy.

The reproducibility of echo-Doppler measurements of portal vein and superior mesenteric artery blood flow has not been extensively studied. In the present study, two groups of subjects were examined to test inter- and intra-observer reproducibility. Each study population consisted of 15 nonportal hypertensive and 15 portal hypertensive subjects. With a standardized technique, the crosssectional area and velocity of blood flow in the portal vein and superior mesenteric artery were recorded in triplicate by skilled operators. The flow volume of each vessel was calculated by multiplying the cross-sectional area by the velocity of blood flow. The measurements were performed in a blind fashion over a 60 min period. The reproducibility of measurements was assessed by calculation of intraclass correlation coefficients and coefficients of variation. The intra-observer intraclass correlation coefficient was 0.77 for portal vein blood flow and 0.84 for superior mesenteric artery blood flow, suggesting good reproducibility. The intra-observer coefficient of variation was 11 and 9%, respectively. In contrast, the interobserver intraclass correlation coefficient was calculated to be 0.49 for portal blood vein blood flow and 0.57 for superior mesenteric artery blood flow, indicating fair reproducibility. In addition, the interobserver coefficients of variation were calculated to be 20 and 18%, respectively. These data suggest that intra-observer reproducibility in echo-Doppler measurements of portal vein and superior mesenteric artery blood flow is acceptable but inter-observer reproducibility is not. Examination by a single operator, rather than multiple operators, is therefore advisable. Even when measurements are performed by a single investigator an approximate variance of 10% in the measurement in a single subject should be expected.

Gastric mucosal hyperemia associated with elevated serum gastrin level has been suggested in cirrhotic patients with portal hypertensive gastropathy (PHG). Clinical evidence has shown that these patients may benefit from propranolol administration. The aim of this study was to investigate effect of propranolol on gastric mucosal perfusion and serum gastrin level in cirrhotic patients with portal hypertensive gastropathy. Gastric mucosal perfusion was assessed by laser Doppler flowmetry. Measurements were performed under basal conditions and after observer-blind administration of propranolol (30-60 mg/day, N = 9) or placebo (N = 9) for seven days. Placebo had no effect on either gastric mucosal perfusion or serum gastrin level. In contrast, propranolol administration significantly decreased both antrum gastric mucosal perfusion (from 0.88 +/- 0.28 to 0.73 +/- 0.26 V, P < 0.05) and corpus gastric mucosal perfusion (from 0.94 +/- 0.35 to 0.78 +/- 0.25 V, P < 0.05). However, this drug had no effect on serum gastrin level. We conclude that chronic propranolol administration in cirrhotic patients with portal hypertensive gastropathy may reduce gastric mucosal perfusion without changing serum gastrin level.

To assess the significance of McCormack's gastric mucosal signs for diagnosing portal hypertension, 100 controls and 100 patients with cirrhosis and portal hypertension underwent endoscopy. Each endoscopic recording was reviewed by multiple blinded observers to reduce bias. Individual signs more frequently observed in patients with cirrhosis and portal hypertension than in controls were fine pink speckling (20% versus 8%, p < 0.05), the snakeskin pattern (30% versus 5%, p < 0.01), and cherry-red spots (15% versus 3%, p < 0.01). In contrast, the prevalence of superficial reddening was similar in the two groups (7% versus 13%, NS). Overall, these gastric mucosal signs also appeared more commonly in patients with portal hypertension than in controls (54% versus 27%, p < 0.01); the sensitivity, specificity, and accuracy of McCormack's signs (overall assessment) for diagnosing portal hypertension were 54%, 73%, and 64%, respectively. Corresponding figures for modified McCormack's signs (exclusion of superficial reddening) were 50%, 85%, and 68%. However, these figures were still lower than those for gastroesophageal varices (72%, 100%, and 86%). We conclude that (1) superficial reddening is not a specific finding in patients with portal hypertension, and (2) gastric mucosal findings are of low sensitivity and specificity for diagnosing portal hypertension compared with gastroesophageal varices.

Portal hypertensive gastropathy is a major complication of cirrhosis. The aims of this study were to characterize portal vein hemodynamics and sympathetic nervous activity in cirrhotic patients with gastropathy. Forty-seven cirrhotics (mild gastropathy in 7) and 25 controls were included in this study. Portal vein hemodynamics was assessed by echo-Doppler, and sympathetic nervous activity by plasma adrenaline and noradrenaline concentrations. Portal blood flow was similar in cirrhotics and controls. However, the congestion index of the portal vein (calculated as the ratio of cross-sectional area and blood velocity) was significantly higher in the former than in the latter. Furthermore, the congestion index of the portal vein paralleled the severity of the gastropathy (ANOVA, p < 0.05). Plasma adrenaline and noradrenaline concentrations were higher in cirrhotics than in controls. However, there was no linear relationship between plasma adrenaline (ANOVA, NS) and noradrenaline (ANOVA, NS) concentrations and the severity of gastropathy. These results suggest a relative contribution of "passive congestion" in the pathogenesis of gastropathy.

The effects of a combination of vasopressin and a calcium channel blocker (nicardipine) on portohepatic hemodynamics and liver function were compared with the effects of vasopressin alone in 18 patients with portal hypertension. Nine patients received 0.4 units/min of vasopressin and 9 patients received the same dose of vasopressin plus 0.3 mg/min of nicardipine for 40 min. Vasopressin plus nicardipine induced a significant reduction in both free portal venous pressure and the portal venous pressure gradient. These effects were similar to the changes with vasopressin alone (-14% vs. -16% in free portal venous pressure; -29% vs. -31% in portal venous pressure gradient). Vasopressin decreased both hepatic blood flow (-34%, P < 0.01) and intrinsic clearance of indocyanine green (-22%, P < 0.05). In contrast, these two parameters did not significantly change after vasopressin plus nicardipine (-8% and -3%, respectively). These results suggest that the addition of nicardipine improves hepatic impairment induced by vasopressin but causes no further reduction on portal pressure.

Although congestive gastric mucosal circulation has been suggested in patients with portal-hypertensive gastropathy, whether it is due to "active" (overflow) or "passive" (stasis) congestion is not known. To answer this question, we assessed regional gastric mucosal blood flow with laser Doppler flowmetry in 57 patients with portal hypertension and 30 controls. Twelve patients had portal-hypertensive gastropathy of the antrum: in eight it was mild and in four it was severe. Portal-hypertensive gastropathy of the corpus was seen in 32 patients: it was mild in 24 and severe in 8. Thus prevalence of portal-hypertensive gastropathy was higher in the corpus than in the antrum (p < 0.01). In the antrum, gastric mucosal blood flow was significantly lower (p < 0.05) in patients with severe portal-hypertensive gastropathy (0.54 +/- 0.27 V) than in controls (1.12 +/- 0.44 V), whereas the values in patients without portal-hypertensive gastropathy (0.90 +/- 0.35 V) and with mild portal-hypertensive gastropathy (0.91 +/- 0.31 V) were not significantly different from the values in controls (p < 0.05 on one-way analysis of variance). In the corpus, gastric mucosal blood flow was significantly lower in patients with mild (0.75 +/- 0.25 V) or severe portal-hypertensive gastropathy (0.42 +/- 0.22 V) than in controls (1.16 +/- 0.37 V) (p < 0.01 and p < 0.01, respectively) whereas the value in patients without portal-hypertensive gastropathy (0.99 +/- 0.37 V) was not significantly different from values in controls (p < 0.01 on one-way analysis of variance).(ABSTRACT TRUNCATED AT 250 WORDS)