Studies On The Effect Of Antioxidants On Cerebral Blood Flow Increment Induced By Prolonged Hyperbaric Oxygen Exposure

Toxic reaction will occur in organism following the inhalation of the gas with exorbitant partial pressure of oxygen(PO₂).If PO₂ was high enough,the toxic reaction would have taken place very fast.The main clinical manifestation of acute oxygen toxicity is the functional disorder of central nervous system(CNS),which is called CNS form oxygen toxicity.One of the most intensive and representative appearance is convulsion grand mal,named "oxygen convulsion"(OC).Acute oxygen toxicity may induce many troubles,such as drowning while diving,which seriously constraint the utilization of oxygen in underwater military mission,underwater performance for commercial purpose and scientific exploration.The recent investigations on the escape of crews from the disabled submarine have pointed out that pre-breathing hyperbaric oxygen(HBO) can enhance the safety factor of crews, and remarkably relieve the condition and sequelae of decompression sickness.In such conditions,very high pressure of oxygen will be used in order to balance the pressure equivalent to the depth of submarine accident.Accordingly,to prevent oxygen convulsion effectively is very valuable for safely and fully utilizing HBO in both military and civilian diving operations.By now, it is not very clear about the mechanism of oxygen convulsion,and the preventive measures are also passive,such as limiting the pressure and the time of HBO exposure. Even the profile used in intermittent HBO exposure,being recognized as the most positive prevention,is empirical,and need much more sufficient scientific evidence to support it.Therefore,intensive investigations on the pathogenesis of oxygen convulsion,especially to determine the key factors directly relating to its onset,is extremely useful no matter for finding out better preventive measures or for optimizing the current intermittent HBO exposure profile.In recent years,studies on the relationship between oxygen convulsion and cerebral blood flow(CBF) variation showed that before the convulsion during prolonged HBO exposure,CBF will always increase abnormally.In the course of intermittent HBO exposure,CBF will rise and fall alternatively according to the periodical conversion of HBO and compressed air.It is just because the periodical decrease of CBF in the period of compressed air exposure can the intermittent HBO exposure postpone the seizure effectively.All these results indicated that the abnormal increase of CBF during prolonged HBO exposure is the pivotal inducement for convulsion.And further studies had showed that NO,especially produced by nNOS in brain tissue,was responsible for the CBF increment.Many studies had showed that reactive oxygen free radicals could impact cerebralvascular activities through influence the metabolism in vascular smooth muscle cells and in endothelial cells.During HBO exposure,a great deal of reactive oxygen free radicals would be formed in vivo.This prompt us to take into account that if these reactive oxygen free radicals also played an important role in the CBF increase before oxygen convulsion.In order to verify the above hypotheses,we investigated the effects of some antioxidants on the variation of CBF during prolonged HBO exposure.We hope these works would be helpful to the investigations on the mechanism of the CBF increment during prolonged HBO exposure,and to further clarifying the relationship between the CBF variation and oxygen convulsion.The works we performed are as follow:1.Different from many other studies,conscious rats instead of anaesthetized rats were used in our investigations.We established an approach of recording electroencephalogram and cerebral blood flow simultaneously and real-timely in conscious rat during hyperbaric exposure.In this way,the interferences to CNS and CBF produced by anesthetic could be diminished.2.We observed the effect of nNOS inhibitor,7-Nitroindazole(7-NI),on the variation of CBF in conscious rat during HBO exposure.3.We investigated the effects of antioxidants,N-acetylcysteine(NAC) and Vit.E,on the variation of CBF in conscious rat during HBO exposure. The main results are as follows:1.During the continuous HBO exposure,the CBF increased abnormally before convulsion in conscious rats.The result demonstrated that the abnormal increase of CBF induced by prolonged HBO exposure is an important cause to convulsion.2.Both the abnormal increase of CBF and convulsion were inhibited by 7-Nitroindazole(30 mg/kg),indicating that NO produced by nNOS is an important cause of CBF increment.3.The abnormal increase of CBF was inhibited remarkably by NAC(100,150,200 mg/kg) and Vit.E,demonstrating that reactive oxygen free radical also has very important effect on the abnormal increase of CBF induced by prolonged HBO exposure.However,NAC and Vit.E had no protective effects against oxygen convulsion.To sum up,our data indicated that NO derivated from nNOS played an important role for the abnormal increase of CBF induced by continuous HBO,and the abnormal increase of CBF is one of the important causes to oxygen convulsion.Our data also showed that apart from NO,reactive oxygen free radical may also have very important effect on the abnormal increase of CBF induced by prolonged HBO exposure.Some antioxidants,such as NAC and Vit.E,could also inhibit the increase of CBF.However,they were ineffective to oxygen convulsion.Such results indicated that the mechanisms of oxygen convulsion were quite complicated.Besides the inducement of CBF increase,there must exist some other inducing factors and pathogenetic mechanism,which were also very important for the seizure and need to be investigated extensively and intensively.