Effect of verapamil on nitric oxide synthase in a portal vein-ligated rat model: role of prostaglandin.

AIM: To investigate the effects of verapamil on nitric oxide (NO) synthesis in a portal vein-ligated rat model. METHODS: Systemic and splanchnic hemodynamics were measured by radiolabeled microspheres in portal hypertensive rats after acute administration of verapamil (2 mg/kg) on chronic treatment with N(w)-nitro-L-arginine (NNA)(80 mg/kg) and/or indomethacin (2 mg/kg). RESULTS: Verapamil (2 mg/kg) caused a marked fall in both arterial pressure and cardiac output accompanied by an insignificant change in the portal pressure and no change in portal venous inflow. This result suggested that verapamil did not cause a reduction in portal vascular resistance of portal hypertensive rats, which was similar between N(w)- nitro-L-arginine-treated and indomethacin-treated groups. CONCLUSION: In portal hypertensive rats pretreated with NNA and/or indomethacin, acute verapamil administration can not reduce the portal pressure, suggesting that NO and prostaglandin play an important role in the pathogenesis of splanchnic arterial vasodilation in portal hypertension.

Abdominal aortic dissection with acute mesenteric ischemia in a patient with Marfan syndrome.

Marfan syndrome is an autosomal dominant inherited disorder of connective tissue, with various complications manifested primarily in the cardiovascular system. It potentially leads to aortic dissection and rupture, these being the major causes of death. We report a patient who complained of acute abdominal pain, which presented as acute mesenteric ischemia combined with abdominal aortic dissection. Echocardiography showed enlargement of the aortic root and mitral valve prolapse. Abdominal computed tomography scan revealed acute mesenteric ischemia due to abdominal aortic dissection. Finally, the patient underwent surgery of aortic root replacement and had a successful outcome. Therefore, we suggest that for optimal risk assessment and monitoring of patients with Marfan syndrome, both aortic stiffness and the diameter of the superior mesenteric vein compared with that of the superior mesenteric artery are useful screening methods to detect acute mesenteric ischemia secondary to abdominal aortic dissection. Early diagnosis and early treatment can decrease the high mortality rate of patients with Marfan syndrome.

Correlation of CYP2C19 genetic polymorphisms with helicobacter pylori eradication in patients with cirrhosis and peptic ulcer.

BACKGROUND: To investigate whether or not CYP2C19 genotype status is associated with cure rate for Helicobacter pylori infection in patients with cirrhosis and peptic ulcer, achieved with 2 weeks of triple therapy with rabeprazole, amoxicillin and clarithromycin. METHODS: We prospectively studied 95 consecutive patients with cirrhosis and H. pylori-infected active peptic ulcers. H. pylori infection was confirmed if any 2 of the following were positive: H. pylori DNA, histology, and rapid urease test. Patients were assigned to an open-label 2-week course of oral amoxicillin 1,000 mg b.i.d., rabeprazole 20 mg b.i.d. and clarithromycin 500 mg b.i.d. Subsequently, all patients received oral rabeprazole 20 mg once daily until week 8. Three months and 1 year after therapy, all patients with cirrhosis were followed up endoscopically for peptic ulcer, rapid urease test, and (13)C-urea breath test. The CYP2C19 genotype status for 2 mutations associated with the extensive metabolizer phenotype was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Cure rates for H. pylori infection were 80.9% (95% CI, 22.8-88.6%), 89.8% (95% CI, 50.8-90.2%), and 100% (95% CI, 62.8-100%) in the rapid-, intermediate-, and poor-metabolizer groups, respectively. Healing rates for duodenal and gastric ulcer in the 3 groups were roughly parallel with cure rates for H. pylori infection. CONCLUSION: The results of the genotyping test for CYP2C19 seem to predict cure of H. pylori infection and peptic ulcer in patients with cirrhosis who receive triple therapy with rabeprazole, amoxicillin, and clarithromycin.

Endoscopic variceal ligation versus propranolol in prophylaxis of first variceal bleeding in patients with cirrhosis.

BACKGROUND AND AIM: To compare the efficacy and safety of endoscopic variceal ligation (EVL) with propranolol in prophylaxis on the rate of first esophageal variceal bleeding in patients with cirrhosis. METHODS: A prospective, randomized trial was conducted in 100 cirrhotic patients with no history of previous upper gastrointestinal bleeding and with esophageal varices endoscopically judged to be at high risk of hemorrhage. The end-points of the study were bleeding and death. RESULTS: Life-table curves showed that prophylactic EVL and propranolol were similarly effective for primary prophylaxis of variceal bleeding (11/50 [22%]vs 12/50 [24%]; P = 0.68) and overall mortality (14/50 [28%]vs 12/50 [24%]; P = 0.49). The 2-year cumulative bleeding rate was 18% (9/50) in the EVL group and 16% (8/50) in the propranolol group. The 2-year cumulative mortality rate was 28% (14/50) in the EVL group and 24% (12/50) in the propranolol group. Comparison of Kaplan-Meier estimates of the time to death of both groups showed no significant difference in mortality in both groups (P = 0.86). Patients undergoing EVL had few treatment failures and died mainly of hepatic failure. In the propranolol group, the mean daily dosage of the drug was 68.2 +/- 32.8 mg, which was sufficient to reduce the pulse rate by 25%. 20% of patients withdrew from propranolol treatment due to adverse events. CONCLUSIONS: Prophylaxis EVL is as effective and as safe as treatment with propranolol in decreasing the incidence of first variceal bleeding and death in cirrhotic patients with high-risk esophageal varices.