M Munk1, F R Poulsen2, L Larsen3, C H Nordström2, T H Nielsen4,5. 1. University of Southern Denmark School of Medicine, Odense, Denmark. 2. Department of Neurosurgery, Odense University Hospital, Odense, Denmark. 3. Department of Infectious Diseases, Odense University Hospital, Odense, Denmark. 4. Department of Neurosurgery, Odense University Hospital, Odense, Denmark. troels@stanford.edu. 5. Department of Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, R209, Stanford, CA, 94305-5327, USA. troels@stanford.edu.
Abstract
BACKGROUND: Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis. METHODS: Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral microdialysis technique and included interstitial glucose, lactate, pyruvate, glutamate, and glycerol. The intracranial pressure (ICP) and brain tissue oxygen tension (PbtO2) were also monitored along with physiological variables including mean arterial pressure, blood glucose, lactate, and partial pressure of O2 and CO2. Pigs were monitored for 60 min at baseline and 240 min after LPS/NaCl injection. RESULTS: After LPS injection, a significant increase in cerebral lactate/pyruvate ratio (LPR) compared to control group was registered (p = 0.01). This increase was due to a significant increased lactate with stable and normal values of pyruvate. No significant change in PbtO2 or ICP was registered. No changes in physiological variables were observed. CONCLUSIONS: The metabolic changes after intracisternal LPS injection is compatible with disturbance in the oxidative metabolism and partly due to mitochondrial dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO2, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed by conventional intensive care monitoring.
BACKGROUND:Cerebral mitochondrial dysfunction is prominent in the pathophysiology of severe bacterial meningitis. In the present study, we hypothesize that the metabolic changes seen after intracisternal lipopolysaccharide (LPS) injection in a piglet model of meningitis is compatible with mitochondrial dysfunction and resembles the metabolic patterns seen in patients with bacterial meningitis. METHODS: Eight pigs received LPS injection in cisterna magna, and four pigs received NaCl in cisterna magna as a control. Biochemical variables related to energy metabolism were monitored by intracerebral microdialysis technique and included interstitial glucose, lactate, pyruvate, glutamate, and glycerol. The intracranial pressure (ICP) and brain tissue oxygen tension (PbtO2) were also monitored along with physiological variables including mean arterial pressure, blood glucose, lactate, and partial pressure of O2 and CO2. Pigs were monitored for 60 min at baseline and 240 min after LPS/NaCl injection. RESULTS: After LPS injection, a significant increase in cerebral lactate/pyruvate ratio (LPR) compared to control group was registered (p = 0.01). This increase was due to a significant increased lactate with stable and normal values of pyruvate. No significant change in PbtO2 or ICP was registered. No changes in physiological variables were observed. CONCLUSIONS: The metabolic changes after intracisternal LPS injection is compatible with disturbance in the oxidative metabolism and partly due to mitochondrial dysfunction with increasing cerebral LPR due to increased lactate and normal pyruvate, PbtO2, and ICP. The metabolic pattern resembles the one observed in patients with bacterial meningitis. Metabolic monitoring in these patients is feasible to monitor for cerebral metabolic derangements otherwise missed by conventional intensive care monitoring.
Authors: Merijn W Bijlsma; Matthijs C Brouwer; E Soemirien Kasanmoentalib; Anne T Kloek; Marjolein J Lucas; Michael W Tanck; Arie van der Ende; Diederik van de Beek Journal: Lancet Infect Dis Date: 2015-12-01 Impact factor: 25.071
Authors: Frantz R Poulsen; Mette Schulz; Anne Jacobsen; Åse B Andersen; Lykke Larsen; Wilhelm Schalén; Troels H Nielsen; Carl-Henrik Nordström Journal: Neurocrit Care Date: 2015-04 Impact factor: 3.210
Authors: Evanna L Mills; Beth Kelly; Angela Logan; Ana S H Costa; Mukund Varma; Clare E Bryant; Panagiotis Tourlomousis; J Henry M Däbritz; Eyal Gottlieb; Isabel Latorre; Sinéad C Corr; Gavin McManus; Dylan Ryan; Howard T Jacobs; Marten Szibor; Ramnik J Xavier; Thomas Braun; Christian Frezza; Michael P Murphy; Luke A O'Neill Journal: Cell Date: 2016-09-22 Impact factor: 41.582