Long-lasting NO overproduction in cirrhotic patients with spontaneous bacterial peritonitis

Abstract

when cirrhosis is decompensated. [2][3][4][5][6] In vivo studies using veNitric oxide production was studied in cirrhotic panous occlusion plethysmography have shown an overproductients with spontaneous bacterial peritonitis (SBP) or tion of NO related to the hyporesponsiveness to vasoconstricwith other infections. We followed up on the time course tors in cirrhotic patients. 7 However, which specific isoform of of serum nitrate levels in 51 hospitalized patients aged NOS accounts for this increment has not been clearly deterbetween 34 and 81 years. Four groups were defined: pamined. To explain vasodilation in cirrhotic patients, Vallance tients with SBP (group 1, n Å 14), patients with bacterand Moncada have hypothesized that endotoxemia might inemia (group 2, n Å 11), patients with urinary tract infecduce the synthesis and release of NO by iNOS, either directly tion (group 3, n Å 11) and patients in a stable clinical or indirectly via cytokines, and this might therefore account condition (group 4, n Å 20). The four groups did not differ for the hyperdynamic circulatory syndrome associated with in terms of Pugh score (11 { 1, 10 { 1, 11 { 1, and 10 { cirrhosis. 8 This is supported by the findings of Guarner et al. 1, respectively). Serum nitrate levels averaged 31 { 2 that serum levels of nitrate correlated with those found in mmol/L in group 4 (84 samples). On the day results of endotoxemia. 4 On the other hand, endothelial constitutive cytobacteriological examination were positive, mean se-NOS was reported to be up-regulated in rats with CCl 4 -inrum nitrate levels were 75 { 17, 63 { 9, and 36 { 9 mmol/ duced cirrhosis, which suggests a major role of this isoform L, respectively, in groups 1 (17 cases), 2 (11 cases), and in the increased production of NO in cirrhotic rats. 9 The last 3 (11 cases) (P õ .001). The maximum nitrate values repossibility is that both isoforms are involved: a mechanical corded during follow-up were higher in groups 1 (149 { stimulation of endothelial constitutive NOS might be second-15 mmol/L) and 2 (112 { 11 mmol/L) than in group 3 (66 ary to increased cardiac output and shear stress, whereas { 7 mmol/L; P õ .001 and õ.01, respectively). These maxianother source of NO might be from iNOS stimulated biomum values were recorded in all groups approximately chemically through cytokines or endotoxins. weeks after the infection was diagnosed. The meanIn a previous study, we found that 1) patients with ascites duration of NO overproduction, as defined by nitrate had higher nitrate levels than those without ascites and 2) level 3 90 mmol/L, was 15 { 3 days in group 1 and 5 { 1 nitrate levels correlated with orosomucoid, a protein of the day in group 2. When the nitrate concentration was studacute-phase response, which suggests that increased nitrate ied in serum and ascitic fluid sampled on the same day, levels were related to activation of iNOS. 6 The high prevait was found to be higher in ascitic fluid than in serum lence of infectious complications in cirrhotic patients with in eight ca...

A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis

“…2,3 Arterial vasodilation is thought to be caused by the release of vasodilator molecules, such as carbon monoxide and NO. 30,31 The decrease in cardiac output is related to a reduction in cardiac preload, an impairment in the chronotropic function of the heart, and perhaps to the cardiomyopathy of cirrhosis aggravated by the deleterious effect of sepsis on myocardial function. 3 As a result, a severe reduction in effective arterial blood volume develops, leading to marked homeostatic activation of the renin-angiotensin and sympathetic nervous systems.…”

“…31,38 There is, therefore, a clear dissociation between the time course of cytokines in plasma and ascitic fluid, the concentration of which decreases markedly after the resolution of the infection, and the plasma and ascitic fluid levels of nitrates and nitrites, which reach the highest levels several days after SBP resolution. 2,31,38 This dissociation is not surprising considering that the inducible form of NO synthase is expressed in many cell types and that the production of NO is maintained over relatively long periods after challenging the cells with immunological or inflammatory stimuli. 38 In our patients treated with HES 200/0.5, we observed a significant increase in the serum levels of nitrates and nitrites despite the resolution of the infection.…”

The diagnostic and predictive value of ascites nitric oxide levels in patients with spontaneous bacterial peritonitis

“…A study performed in a small number of patients with alcoholic liver disease showed that serum nitrate levels were higher in patients with SBP compared with patients without infection. 4 On the other hand, experimental studies suggest that NO may have a protective role in the pathogenesis of SBP, 5,6 and therefore, ascites NO levels could also be used as a predictor of the development of SBP.…”

Renal Dysfunction in Liver Transplant Candidates: Evaluation, Classification and Management in Contemporary Practice

“…Renal failure associated with refractory ascites can develop slowly within several weeks or months (type 2 HRS), or it can develop abruptly in less than 2 weeks when it is often associated with SBP (type 1 HRS). Peritonitis causes a severe inflammatory response with production of vasoactive mediators, worsening the circulatory dysfunction and precipitating acute renal failure [17]. This mechanism explains the strong association between ascites and acute renal failure, especially in the setting of SBP [8].…”