Changes of plasma D(-) -lactate, diamine oxidase and endotoxin in patients with liver cirrhosis

BACKGROUND: Plasma D(-)-lactate and diamine oxidase (DAO) can reflect patients' intestinal mucosal condition. We evaluated the changes of plasma D (-)-lactate, DAO and endotoxin activities and their significance in patients with liver cirrhosis. METHODS: Fifty liver cirrhosis patients were enrolled into experimental group and 30 healthy people into control group. The plasma levels of D(-)-lactate, DAO and endo- toxin were detected spectrophotographically. RESULTS: The level of D(-)-lactate was significantly high- er in the experimental group than that in the control group (P<0.01). Significant differences of D (-)-lactate levels were observed in Child-Pugh subgroups of the experimen- tal group (P <0. 01). The level of DAO was significantly higher in the experimental group than that in the control group (P <0.01), but the level of DAO in Child-Pugh sub- group C was significantly lower than that in Child-Pugh subgroup B (P<0.01). The level of endotoxin was signifi- cantly increased in the experimental group except Child Pugh subgroup A (P<0.01). The plasma levels of D(-) lactate, DAO and endotoxin were positively correlated with each other (P<0.01). CONCLUSIONS: The data suggest that both plasma D(-) lactate and DAO activity are sensitive markers for early diagnosis of gut failure and endotoxemia in patients with liver cirrhosis. The impairment of intestinal barrier func- tion may be one of the critical reasons for deterioration of liver cirrhosis.

Relationship between plasma D(-)-lactate and intestinal damage after severe injuries in rats

AIM To explore the kinetic changes in plasma D(-)- lactate and lipopolyssccharide(LPS)levels,and investigate whether D(-)-lactate could be used as a marker of intestinal injury in rats following gut ischemia/ reperfusion,burn,and acute necrotizing pancreatitis (ANP). METHODS Three models were developed in rats:① gut ischemia/ reperfusion obtained by one hour of superior mesenteric artery occlusion followed by reperfusion;② severe burn injury created by 30% of total body surface area(TBSA)full-thickness scald burn;and ③ ANP induced by continuous inverse infusion of sodium taurocholate and trypsin into main pancreatic duct. Plasma levels of D(-)-lactate in systemic circulation and LPS in portal circulation were measured by enzymatic- spectrophotometric method and limulus amebocyte lysate (LAL)test kit,respectively.Tissue samples of intestine were taken for histological analysis. RESULTS One hour gut ischemia followed by reperfusion injuries resulted in a significant elevation in plasma D(-)- lactate and LPS levels,and there was a significant correlation between the plasma D(-)-lactate and LPS(r =0.719,P<0.05).The plasma concentrations of D(-)- lactate and LPS increased significantly at 6h postburn, and there was also a remarkable correlation between them (r = 0.877,P < 0.01).D(-)-lactate and LPS levels elevated significantly at 2h after ANP,with a similar significant correlation between the two levels(r = 0.798, P < 0.01 ).The desquamation of intestine villi and infiltration of inflammatory cells in the lamina propria were observed in all groups. CONCLUSION The changes of plasma D(-)-lactate levels in systemic blood paralleled with LPS levels in the portal vein blood.The measurement of plasma D(-)-lactate level may be a useful marker to assess the intestinal injury and to monitor an increase of intestinal permeability and endotoxemia following severe injuries in early stage.

TNF-α and plasma D(-)-lactate levels in rats after intestinal ischemia and reperfusion

Objective To study the potential role of tumor necrosis factor-α (TNF-α) induction in the development of mucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury, and to examine whether pretreatment with monoclonal antibody against TNF-α (TNF-α MoAb) would affect the release of D(-)-lactate after local gut ischemia followed by reperfusion. Methods Anesthetized Sprague-Dawley rats underwent superior mesenteric artery occlusion for 75 min followed by reperfusion for 6 hr. The rats were treated intravenously with either TNF-α MoAb (20 mg/kg) or albumin (20 mg/kg) 30 min prior to the onset of ischemia. Plasma D(-)-lactate levels were measured in both the portal and systemic blood by an enzymatic spectrophotometric assay. Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals. In addition, a postmortem examination was performed together with a macropathological evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in both the control and treatment groups ( P ＜0.05). However, animals pretreated with TNF-α MoAb at 6 hr after reperfusion showed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with those only receiving albumin (P ＜ 0.05). In the control animals, a remarkable rise in intestinal TNF-α level was measured at 0.5 hr after clamp release ( P ＜ 0.01); however, prophylactic treatment with TNF-α MoAb completely annulled the increase of local TNF-α levels seen in the control animals. Similarly, after anti-TNF-α MoAb administration, intestinal TNF-α mRNA expression was markedly inhibited, which showed significant differences when compared with the control group at 0.5 hr, 2 hr and 6 hr after the release of occlusion ( P ＜ 0.05-0.01 ). In addition, the pathological examination showed marked intestinal lesions that formed during ischemia, which were much worse upon reperfusion,particularly at the 6 hr time point. These acute injuries were obviously attenuated in animals receiving TNF-α MoAb.Conclusions It appeared that acute intestinal ischemia was associated with failure of the mucosal barrier, resulting in increased plasma D(-)-lactate levels in both portal and systemic blood. These results suggest that TNF-α appears to be involved in the development of local damage associated with intestinal ischemic injury. Moreover, prophylactic treatment with TNF-α MoAb exerts preventive effects on ischemia/ reperfusion-induced circulating D (-)-lactate elevation and gut injury. ( J Geriatr Cardiol 2004;1(2):119-124. )