Relationship Of Cerebral Energy Metabolism And Microcirculation Under Acute Hypoxia

Brain is the vital control center of the body to maintain life activities. The human brain contains about100billion neurons. All those neural activities required energy, which is from the brain’s blood and oxygen supply. This large and complex system is closely related to brain microcirculation and metabolism, which attracts sustained attention from researchers. With the development of science and technology, a variety of research tools have emerged, revealing the dynamic relationship between energy metabolism and brain microcirculation from blood oxygen and tissue levels, mitochondrial level, and molecular level, respectively. Energy metabolism occurs in the cells, and the mitochondria are the main energy engine. Reduced nicotinamide adenine dinucleotide (NADH) has been suggested to be the most sensitive indicator of mitochondrial redox state due to its location at the very beginning of the respiration chain and capability of autofluorescence, which can be utilized to illustrate energy metabolism of cells. Also, the systemic circulation and regional circulation usually change the brain microcirculation, thus affecting the energy metabolism. Therefore, simultaneous measurement of changes in the systemic circulation, can provide a more comprehensive explanation of the changes in energy metabolism which are affected by changes in the microcirculation.Based on the NADH fluorescence measurement system developed by Chance and Mayevsky, this thesis established a new cross-level, multi-parametric monitoring method to achieve a synchronous detection of NADH fluorescence, reflectance at the excitation wavelength, and cerebral blood flow velocity in the cerebral rat cortex, and systemic parameters of respiration and Electrocardiograph (ECG). In order to systematically study the relationship between brain energy metabolism and microcirculation,4typical and6acute hypoxia models with varying causes were investigated, including hypoxic hypoxia, hypaemic hypoxia, circulatory hypoxia and histogenous hypoxia. Detailed analysis of the signal changes at mitochondrial, microcirculatory, and systemic levels was discussed. From the order of time of occurrence the interaction between metabolism and microcirculation can be speculated.The results in this thesis confirm that:under normal anesthesia, metabolic status of rat brain cortex is between66.1%～73.0%; at the time of death, cerebral cortex NADH can rise to136.9%-151.4%; during hypoxia, cerebral blood flow increased to a maximum (195.5±14.9)%, while the largest increase cerebral blood volume does not exceed (55.0±2.4)%. Changes in cerebral blood flow are more than the magnitude of cerebral blood volume.Regarding the question whether there is new capillaries recruitment occurred under hypoxia, the thesis found that in the hypoxic and hypaemic hypoxia models, cerebral blood volume responded earlier than cerebral blood flow velocity, which supported the view that at this time the change of cerebral blood volume is due to the recruitment of the regional capillaries.From the five monitered parameters, the thesis analyzed the relationship between energy metabolism and microcirculation. The results showed that, the time of NADH responded to hypoxia are related to the hypoxia types, e.g. the causes of hypoxia.NADH responded earlier than cerebral blood volume and cerebral blood flow, indicating the regional energy metabolism changed earlier than microcirculation. Also due to the different hypoxia causes, NADH signal can not maintain its advantage of earliest response. But in this case the multi-parametric monitoring can compensate for the risk of miss detection.Through the four typical and six models of acute hypoxia studies, this thesis suggested that NADH parameter is significant to clinical diagnosis, because NADH signals alarmed to death earlier than other parameters. If taking right rescue and restore oxygen supply, the body can be saved from death. Therefore, right judgment to determine the time that NADH reached its ultimate value and right diagnosis of hypoxia type (cause) is particularly important for clinical intensive care. This study suggested, NADH increased to130%, or enter a significant platform can be regarded as one of the alarms. Since the monitored object and organs have different redox state properties, the specific alarm levels need further study to determine. Similarly, the right judgment to the hypoxia type (cause) needs integrated consideration of multi-parametric variations.