Cerebrospinal Fluid Lactate in Patients with Hepatic Encephalopathy

Yao, Hiroshi; Sadoshima, Seizo; Fujii, Kenichiro; Kusuda, Kenji; Ishitsuka, Takao; Tamaki, Koichi; Fujishima, Masatoshi

doi:10.1159/000116153

Cited by 45 publications

(18 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover in acute liver failure, therapeutic interventions, such as mild hypothermia and albumin dialysis, have shown to reduce cerebral lactate along with brain edema and the development of severe HE (coma and intracranial hypertension) [24], [27] and [28]. Furthermore, in the setting of CLD, a 1.37-fold increase in lactate in the cerebrospinal fluid has been found in patients with end-stage liver disease and overt/severe HE (grades 3 and 4) [29]. Chronic hyperammonemic rats (induced following 4-week portacaval anastomosis) injected with a toxic dose of ammonia precipitates severe HE (coma), which is accompanied with brain edema and an increase in brain lactate [30] and [31].…”

Section: Discussionmentioning

confidence: 99%

Increased brain lactate is central to the development of brain edema in rats with chronic liver disease

Bosoi

Zwingmann

Marin

et al. 2014

Journal of Hepatology

View full text Add to dashboard Cite

The pathogenesis of brain edema in patients with chronic liver disease (CLD) and minimal hepatic encephalopathy (HE) remains undefined. This study evaluated the role of brain lactate, glutamine and organic osmolytes, including myo-inositol and taurine, in the development of brain edema in a rat model of cirrhosis.Six-week bile-duct ligated (BDL) rats were injected with (13)C-glucose and de novo synthesis of lactate, and glutamine in the brain was quantified using (13)C nuclear magnetic resonance spectroscopy (NMR). Total brain lactate, glutamine, and osmolytes were measured using (1)H NMR or high performance liquid chromatography. To further define the interplay between lactate, glutamine and brain edema, BDL rats were treated with AST-120 (engineered activated carbon microspheres) and dichloroacetate (DCA: lactate synthesis inhibitor).Significant increases in de novo synthesis of lactate (1.6-fold, p<0.001) and glutamine (2.2-fold, p<0.01) were demonstrated in the brains of BDL rats vs. SHAM-operated controls. Moreover, a decrease in cerebral myo-inositol (p<0.001), with no change in taurine, was found in the presence of brain edema in BDL rats vs. controls. BDL rats treated with either AST-120 or DCA showed attenuation in brain edema and brain lactate. These two treatments did not lead to similar reductions in brain glutamine.Increased brain lactate, and not glutamine, is a primary player in the pathogenesis of brain edema in CLD. In addition, alterations in the osmoregulatory response may also be contributing factors. Our results suggest that inhibiting lactate synthesis is a new potential target for the treatment of HE.Canadian Institutes of Health Research. CB:Fonds de recherche du Québec – Sant

show abstract

Section: Discussionmentioning

confidence: 99%

Increased brain lactate is central to the development of brain edema in rats with chronic liver disease

Bosoi

Zwingmann

Marin

et al. 2014

Journal of Hepatology

View full text Add to dashboard Cite

show abstract

“…25,26 In agreement with this, a human PET study found no correlation between CMRA and brain glucose utilization, although a correlation between ammonia uptake and changes in brain metabolites on magnetic resonance spectroscopy was observed, indicating some effects of ammonia in vivo. 27 Cerebral metabolites such as lactate have been found to be increased in animal models 8,21 and in cerebrospinal fluid from patients with HE, 22 which may indicate increased glycolysis, but whether increased lactate is a cause or consequence of HE is uncertain. 23 Thus, although we were unable to link the decrease in CMRO 2 to an increase in CMRA, we cannot rule out that ammonia may be involved in the pathogenesis of HE, perhaps through subtle effects on energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

et al. 2013

View full text Add to dashboard Cite

Studies have shown decreased cerebral oxygen metabolism (CMRO 2 ) and blood flow (CBF) in patients with cirrhosis with hepatic encephalopathy (HE). It remains unclear, however, whether these disturbances are associated with HE or with cirrhosis itself and how they may relate to arterial blood ammonia concentration and cerebral metabolic rate of blood ammonia (CMRA). We addressed these questions in a paired study design by investigating patients with cirrhosis during and after recovery from an acute episode of HE type C. CMRO 2 , CBF, and CMRA were measured by dynamic positron emission tomography (PET)/computed tomography (CT). Ten patients with cirrhosis were studied during an acute episode of HE; nine were reexamined after recovery. Nine patients with cirrhosis with no history of HE served as controls. Mean CMRO 2 increased from 0.73 lmol oxygen/mL brain tissue/min during HE to 0.91 lmol oxygen/mL brain tissue/min after recovery (paired t test; P < 0.05). Mean CBF increased from 0.28 mL blood/mL brain tissue/min during HE to 0.38 mL blood/mL brain tissue/min after recovery (P < 0.05). After recovery from HE, CMRO 2 and CBF were not significantly different from values in the control patients. Arterial blood ammonia concentration decreased 20% after recovery (P < 0.05) and CMRA was unchanged (P > 0.30); both values were higher than in the control patients (both P < 0.05). Conclusion: The low values of CMRO 2 and CBF observed during HE increased after recovery from HE and were thus associated with HE rather than the liver disease as such. The changes in CMRO 2 and CBF could not be linked to blood ammonia concentration or CMRA. (HEPATOLOGY 2013;57:258-265) B rain energy metabolism is believed to be disturbed in patients with cirrhosis with hepatic encephalopathy (HE).1 Studies have shown decreased cerebral oxygen consumption (CMRO 2 ) and blood flow (CBF) in patients with cirrhosis and HE when compared to patients with cirrhosis without HE or healthy subjects, whereas the latter two groups of subjects had similar values.2-5 Cross-sectional studies point to the reductions being related to the HE condition and not to the liver disease itself. 4,5 In accordance with this, one study reported that reductions in CMRO 2 and CBF were restored when patients, treated with a dopamine agonist, recovered from HE.3 Another study, however, found decreased CMRO 2 but unchanged CBF in patients with a history of HE when compared to patients without a history of HE or healthy controls.6 It thus remains an open question whether the reductions in CMRO 2 and CBF in patients with cirrhosis and HE normalize after recovery from HE, and in the present study we therefore measured CMRO 2 and CBF during and after recovery from an episode of HE in individual patients with cirrhosis.Another key question is how changes in CMRO 2 and CBF may relate to the blood concentration of ammonia. Patients with cirrhosis with HE usually have higher Abbreviations: CBF, cerebral blood flow; CMRA, cerebral metabolic rate of blood ammonia; CMRO 2 , cerebral o...

show abstract

“…Furthermore, mild hypothermia prevents both brain edema and the accumulation of lactate in CSF in ALF. On the other hand, increased brain lactate is a feature that is common to both acute (Hawkins et al, 1973;Holmin et al, 1983) and chronic (Hindfelt et al, 1977;Therrien et al, 1991;Yao et al, 1987) liver failure and brain edema is generally confined to the acute condition. It is conceivable that compensatory mechanisms occur in chronic liver failure, which render the astrocytes less vulnerable to lactate-induced swelling.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Chatauret

Rose

Therrien

et al. 2001

Metabolic Brain Disease

View full text Add to dashboard Cite

Chatauret, N. et al., 2001. Mild hypothermia prevents cerebral edema and CSF lactate accumulation in acute liver failure. Metabolic Brain Disease, ABSTRACT Evidence from both clinical and experimental studies demonstrates that mild hypothermia prevents encephalopathy and brain edema in acute liver failure (ALF). As part of a series of studies to elucidate the mechanism(s) involved in this protective effect, groups of rats with ALF resulting from hepatic devascularization were maintained at either 37°C (normothermic) or 35°C (hypothermic), and neurological status was monitored in relation to cerebrospinal fluid (CSF) concentrations of ammonia and lactate. CSF was removed via implanted cisterna magna catheters. Mild hypothermia resulted in a delay in onset of encephalopathy and prevention of brain edema; CSF concentrations of ammonia and lactate were concomitantly decreased. Blood ammonia concentrations, on the other hand, were not affected by hypothermia in ALF rats. These findings suggest that brain edema and encephalopathy in ALF are the consequence of ammonia-induced impairment of brain energy metabolism and open the way for magnetic resonance spectroscopic monitoring of cerebral function in ALF. Mild hypothermia could be beneficial in the prevention of severe encephalopathy and brain edema in patients with ALF awaiting liver transplantation.

show abstract

Cerebrospinal Fluid Lactate in Patients with Hepatic Encephalopathy

Cited by 45 publications

References 17 publications

Increased brain lactate is central to the development of brain edema in rats with chronic liver disease

Increased brain lactate is central to the development of brain edema in rats with chronic liver disease

Hepatic encephalopathy is associated with decreased cerebral oxygen metabolism and blood flow, not increased ammonia uptake

Untitled

Contact Info

Product

Resources

About