SERUM AND URINARY NITRATE LEVELS IN LIVER-CIRRHOSIS - ENDOTOXEMIA, RENAL-FUNCTION AND HYPERDYNAMIC CIRCULATION

Background/Aims: The relationship between nitric oxide production, end otoxemia, renal function and hyperdynamic circulatory syndrome has not been yet investigated in patients with cirrhosis. Methods: Serum and urine nitrate, endotoxemia and cardiac index were measured in 59 patie nts with cirrhosis. Results: Patients with a tense ascites had higher serum nitrate levels than healthy control subjects (39+/-7 vs 19+/-4 m u mol/l, p<0.01), Patients with mild ascites and without ascites had n ormal values of nitrate levels. In the group of patients not treated w ith diuretics (n=38), creatinine and nitrate clearances were lower in ascitic patients than in nonascitic patients (respectively 0.82+/-0.12 vs 1.48+/-0.32 ml/s, p<0.02 and 0.30+/-0.07 vs 2.89+/-2.04 ml/s, p<0. 05). Endotoxin levels were higher in patients with cirrhosis than in c ontrol subjects and paralleled the severity of liver failure (Child A/ B/C vs control subjects: 0.056+/-0.014/0.064+/-0.005/0.090+/-0.008 vs 0.027+/-0.005 Endotoxin Units/ml, p<0.001). Serum nitrate levels did n ot correlate with endotoxemia (r=-0.110). On the other hand, levels of orosomucoid, a protein synthesized by the liver in response to a stim ulation by cytokines correlated with those of nitrate (respectively r= 0.343, p<0.01). Hemoglobin levels were negatively correlated with seru m nitrate levels (r=-0.328 p<0.02). Cardiac index was higher in patien ts than in control subjects and paralleled the degree of liver failure (Child A/B/C vs control subjects: 3.60+/-0.25/4.10+/-0.19/4.47+/-0.25 vs 3.15+/-0.12 1 . min . m(2), p<0.001). Cardiac index did not correl ate with serum nitrate levels, urine nitrate excretion and endotoxemia . Conclusions: Renal impairment accounts for the increased levels of s erum nitrate in ascitic patients, A stimulation of nitric oxide produc tion by cytokines may occur but endotoxemia is not involved in such a mechanism. Anemia has a role in nitric oxide activity. Nitric oxide ge neration assessed by nitrate in serum and urine does not seem to parti cipate in the hyperdynamic circulatory syndrome in patients with cirrh osis.