BACKGROUND: In patients with cirrhosis, portosystemic shunts allow intestinal bacteria and endotoxin to enter the systemic circulation. Endotoxemia may induce increased synthesis of nitric oxide, thereby contributing to arterial vasodilation. OBJECTIVE: To test the hypothesis that the antibiotic norfloxacin blocks the effects of nitric oxide. DESIGN:Placebo-controlled, double-blind, crossover study. SETTING: Alfred Hospital, Melbourne, Australia. PATIENTS: 9 patients with alcohol-related cirrhosis and 10 healthy controls. INTERVENTION: Norfloxacin, 400 mg twice daily, for 4 weeks. MEASUREMENTS: Peripheral blood flow was measured by using forearm venous occlusion plethysmography. RESULTS:Basal forearm blood flow was higher in patients with cirrhosis than in controls (3.69 +/- 0.27 mL/100 mL per minute and 2.47 +/- 0.40 mL/100 mL per minute; P = 0.014) but returned toward normal after norfloxacin was given (2.64 +/- 0.31 mL/100 mL of tissue per minute in patients with cirrhosis). Responses to NG-monomethyl-L-arginine were greater in patients with cirrhosis but returned to normal after norfloxacin was given. CONCLUSION: Bacterial endotoxemia in patients with cirrhosis induces increased synthesis of nitric oxide that can be corrected with norfloxacin.
RCT Entities:
BACKGROUND: In patients with cirrhosis, portosystemic shunts allow intestinal bacteria and endotoxin to enter the systemic circulation. Endotoxemia may induce increased synthesis of nitric oxide, thereby contributing to arterial vasodilation. OBJECTIVE: To test the hypothesis that the antibiotic norfloxacin blocks the effects of nitric oxide. DESIGN: Placebo-controlled, double-blind, crossover study. SETTING: Alfred Hospital, Melbourne, Australia. PATIENTS: 9 patients with alcohol-related cirrhosis and 10 healthy controls. INTERVENTION: Norfloxacin, 400 mg twice daily, for 4 weeks. MEASUREMENTS: Peripheral blood flow was measured by using forearm venous occlusion plethysmography. RESULTS: Basal forearm blood flow was higher in patients with cirrhosis than in controls (3.69 +/- 0.27 mL/100 mL per minute and 2.47 +/- 0.40 mL/100 mL per minute; P = 0.014) but returned toward normal after norfloxacin was given (2.64 +/- 0.31 mL/100 mL of tissue per minute in patients with cirrhosis). Responses to NG-monomethyl-L-arginine were greater in patients with cirrhosis but returned to normal after norfloxacin was given. CONCLUSION: Bacterial endotoxemia in patients with cirrhosis induces increased synthesis of nitric oxide that can be corrected with norfloxacin.