Cerebral energy metabolism during induced mitochondrial dysfunction

TY - JOUR

T1 - Cerebral energy metabolism during induced mitochondrial dysfunction

AU - Nielsen, T H

AU - Bindslev, TT

AU - Pedersen, S M

AU - Toft, P

AU - Olsen, Niels Vidiendal

AU - Nordström, C H

N1 - © 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.

PY - 2013/2

Y1 - 2013/2

N2 - Background In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in brain tissue oxygen tension (PbtO2) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets. Methods Ten piglets were included, seven in the experimental group (anesthetized with sevoflurane) and three in the control group (anesthetized with midazolam). PbtO2 and cerebral levels of glucose, lactate, and pyruvate were monitored bilaterally. The biochemical variables were obtained by intracerebral microdialysis. Results All global variables were within normal range and did not differ significantly between the groups except for blood lactate that was slightly higher in the experimental group. Mitochondrial dysfunction was observed in the group of animals initially anesthetized with sevoflurane. Cerebral glucose was significantly lower in the experimental group than in the control group whereas lactate and lactate/pyruvate ratio were significantly higher. Pyruvate and tissue oxygen tension remained within normal range in both groups. Changes of intracerebral variables indicating mitochondrial dysfunction were present already from the very start of the monitoring period. Conclusion Intracerebral microdialysis revealed mitochondrial dysfunction by marked increases in cerebral lactate and lactate/pyruvate ratio simultaneously with normal levels of pyruvate and a normal PbtO2. This metabolic pattern is distinctively different from cerebral ischemia, which is characterized by simultaneous decreases in PbtO2 and intracerebral pyruvate.

AB - Background In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in brain tissue oxygen tension (PbtO2) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets. Methods Ten piglets were included, seven in the experimental group (anesthetized with sevoflurane) and three in the control group (anesthetized with midazolam). PbtO2 and cerebral levels of glucose, lactate, and pyruvate were monitored bilaterally. The biochemical variables were obtained by intracerebral microdialysis. Results All global variables were within normal range and did not differ significantly between the groups except for blood lactate that was slightly higher in the experimental group. Mitochondrial dysfunction was observed in the group of animals initially anesthetized with sevoflurane. Cerebral glucose was significantly lower in the experimental group than in the control group whereas lactate and lactate/pyruvate ratio were significantly higher. Pyruvate and tissue oxygen tension remained within normal range in both groups. Changes of intracerebral variables indicating mitochondrial dysfunction were present already from the very start of the monitoring period. Conclusion Intracerebral microdialysis revealed mitochondrial dysfunction by marked increases in cerebral lactate and lactate/pyruvate ratio simultaneously with normal levels of pyruvate and a normal PbtO2. This metabolic pattern is distinctively different from cerebral ischemia, which is characterized by simultaneous decreases in PbtO2 and intracerebral pyruvate.

KW - Anesthesia, Inhalation

KW - Anesthetics, Inhalation

KW - Animals

KW - Blood Gas Analysis

KW - Blood Pressure

KW - Body Temperature

KW - Brain Chemistry

KW - Cytoplasm

KW - Energy Metabolism

KW - Female

KW - Glucose

KW - Intracranial Pressure

KW - Lactic Acid

KW - Methyl Ethers

KW - Mitochondrial Diseases

KW - Oxidation-Reduction

KW - Oxygen Consumption

KW - Pyruvic Acid

KW - Swine

U2 - 10.1111/j.1399-6576.2012.02783.x

DO - 10.1111/j.1399-6576.2012.02783.x

M3 - Journal article

C2 - 23017022

SN - 0001-5172

VL - 57

SP - 229

EP - 235

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

IS - 2

ER -