Influence of moderate hypothermia on cerebral oxygenation in pigs with intracranial hypertension

BACKGROUND： Moderate hypothermia is one of the effective therapeutic methods for head injury in recent years, there are many mechanisms of moderate hypothermia for brain protection, and its influence on cerebral oxygenation is also one of them. OBJECTIVE： To observe the influence of moderate hypothermia on cerebral oxygenation of animals with acute intracranial hypertension, and further investigate the protective mechanism of moderate hypothermia. DESIGN： A randomized controlled trial. SETTING： Department of Neurosurgery, Renji Hospital affiliated to the Medical College of Shanghai Jiao Tong University. MATERIALS： Twenty healthy little pigs, either male or female, weighing 4.5-5.5 kg, were used. Neurotrend-typed multiparameter monitoring system （Diametrics Company, British）; CMA/100 micro-injection pump （Carnegie Company, Sweden）. METHODS： The experiment was conducted in the Changzheng Hospital affiliated to the Second Military Medical University of Chinese PLA in November, 2001. The pigs were randomized into two groups： the normothermia group （control group, n =10） and moderate hypothermia group （n =10）. ① Bilateral femoral arteries were separated, one was connected to pressometer for monitoring mean arterial pressure （MEP）, and the other for analysis of blood gases [including peripheral blood pH value, arterial partial pressure of carbon dioxide （PaCO2）, arterial partial pressure of carbon dioxide （PaCO2）, HCO3-]. ② Rectal temperature was monitored with mercurial thermometer. ③ Intracranial pressure was monitored using Camino optic ICP probe placed in the subdural space. ④ Neurotrend multiparameter monitoring sensor was inserted into the white matter for about 4 cm to determine cerebral perfusion pressure （CPP, CPP=MAP（ICP）, brain tissue partial oxygen pressure （PO2）, partial pressure of carbon dioxide （PCO2）, HCO3- and brain temperature. The rectal temperature of animals in the moderate hypothermia group was lowered to 34 ℃ using ice bags, and the body temperature was maintained at 33-35 ℃ for 2 hours. The changes of the parameters were observed continuously, and the pigs in the normothermia group were not treated with cooling. MAIN OUTCOME MEASURES： ① MAP, ICP, rectal temperature, CCP; Indexes of cerebral oxygenation detected with Neurotrend-typed multiparameter monitoring system; ② Results of blood gases analysis in the moderate hypothermia group. RESULTS： All the 20 pigs were involved in the analysis of results. ① MAP, ICP, rectal temperature, CCP and indexes of cerebral oxygenation： In the moderate hypothermia group, the ICP after cooling was obviously lower than that before cooling [（3.31±1.19）, （5.33±0.95） kPa, P 〈 0.05], CCP was higher, brain tissue PCO2 [（12.03±1.73）, （10.59±2.01） kPa, P 〈 0.05], and brain tissue pH value was higher [（7.03± 1.63）, （9.40±1.30） kPa, P 〈 0.05], whereas the brain temperature was decreased as compared with that before cooling [（34.9±0.3）, （37.2±0.2） ℃, P 〈 0.05]. ② Results of blood gases analysis in the moderate hypothermia group： There were no significant differences in the parameters of peripheral arterial blood gases analysis before and after cooling in the moderate hypothermia group （P 〉 0.05） CONCLUSION： Moderate hypothermia will not impair the cerebral oxygenation, and it can reduce brain tissue CO2 and decrease brain tissue acidosis.

HYPERBARIC HYPEROXIA AND THE BRAIN IN VIVO:THE BALANCE BETWEEN THERAPY AND TOXICITY

Hyperbaric oxygenation(HBO)treatment protocols utilize low pressures up to 3ATA.Higher pressures may induce side effects such as convulsions due to brain toxicity.The optimal HBO pressure allowing for maximal therapy and minimal toxicity is under controversy.However,it can be evaluated by monitoring oxygen delivery,saturation,and consumption.In this study,the monitoring system fixed on the rats’brain cortex included a time-sharing fluorometer-reflectometer for monitoring mitochondrial NADH and hemoglobin oxygenation(HbO_(2))combined with Laser Doppler Flowmetry(LDF)for blood-flow monitoring.Rats were located in a hyperbaric chamber and exposed to different pressures.The HBO pressure caused an increase in HbO_(2)and a decrease in NADH in proportion to the increase in hyperbaric pressure,up to a nearly maximum effect at 2.5ATA.At 6ATA,15 minutes before convulsions started,blood volume and NADH started to increase,while tissue O_(2)supply by hemoglobin remained stable.Oxygen pool includes oxygen dissolved in the plasma and also bounded to hemoglobin.Above 2.5ATA,hemoglobin is fully saturated and the oxygen pool nourishment derives only from the oxygen dissolved in the plasma,exceeding the physiological ability for autoregulation;hence,homeostasis is disturbed and convulsions appear.This information is vital because pressures around 2.5ATA–3ATA are standard clinically applied pressures used to treat most of the pathophysiological problems considering the potential benefit which must be balanced against the potential toxicity.This study enables,for the first time,to evaluate the oxygenation level of hemoglobin in the microcirculation.Furthermore,our study showed that additional oxygen pressure(above 2.5ATA)caused brain oxygen toxicity within a short variable period of time after the pressure elevation.

Signals Analysis and Clinical Validation of Blood and Oxygen Data in Human Brain

With a self-made near-infrared analytical instrument to blood and oxygen parameters in human brain, 80 cases in which 20 are healthy persons and 30 are anaesthetised cases and others are patients with heart function lack is taken to examine, and the data of blood and oxygen in brain tissue were collected and analyzed by the method of power spectrum and correlation function. The results indicate that: (1) The average brain oxygen saturation of healthy persons and anaesthetised cases is about 80%, in accord with normal parameter of physiology. Contrastively, the average brain oxygen saturation of patients with heart function lack is 72.8%, which is obviously less than that of healthy persons and anaesthetised cases. The probability of medical statistics is less than 0.01. (2) The shapes of wave of brain blood and oxygen for the healthy person and the anaesthetised case reveal small periodical fluctuations with stable shape and base line, and the trend of increase or decrease of blood and oxygen parameters in brain tissue is synchronous and a phase reversal, but for the patient with heart function lack in a brain oxygen lack state, the shapes of wave are irregular. This is a hint that near infrared light passing through tissue can reflect the intuitionistic change of brain blood and oxygen parameters.(3) The power spectra of brain blood and oxygen for the healthy person and the anaesthetised case has a clear main peak, narrow bandwidth and perfect superposition each other, but the power spectra for the patient with heart function lack in a brain oxygen lack state is on the contrary.(4) The average cross correlation coefficient of brain blood and oxygen for healthy persons and anaesthetised cases is -0.9825±0.1027 close to -1. But the average cross correlation coefficient for patients with heart function lack in a brain oxygen lack state is merely -0.8923±0.1035 which is obviously greater than -1 and the probability of medical statistics is less than 0.01. The clinic experiments have proved that the shapes of waves, the power spectrum and cross correlation coefficient of brain blood and oxygen are useful to analyze the physiological status and changes of blood and oxygen in human brain.