Investigation Of Protective Effects Of 7-nitroindinazole On Brain In Rats Undergoing Deep Hypothermic Circulatory Arrest

Objective:The technique of deep hypothermic circulatory arrest(DHCA)was widely applied in cardiac surgery now.But the safe time of DHCA was only 45～60 minutn.To investigate the mechamism of brain scathe and the way to prolong the safe time of DHCA became very important.The protective role of neuraonal nitric oxide synthase (nNOS)inhibitor 7-nitroindinazole(7-NI)on the focal cerebral ischemi has been found out.However,the effectiveness of 7-NI on brain undergoing DHCA has not been reported.The effect of 7-NI on ischemia edema,structure and contents of MDA and nitric oxide synthase(NOS)in cerebral were studied by using the model DHCA in rats.Methods:Two hundred SD rats were randomly divided into 5 groups:group A:fake operation group(n=16),group B:DHCA group (n=46),group C:DHCA+7-NI group(n=46),group D:DHCA+L-Arg group(n=46),group E:arachisoil group(n=46).The last 4 groups were each divided into 4 subgroups according to the time phase after DHCA,witch was 2h(n=10),6h(n=10),12h(n=10),24h(n=16). Imbedding rats by ice cubes to reduce the temperature and occlusion both common carotid arteries while the temperature reach 21℃.The effect of 7-nitroindinazole(7-NI)on ischemia edema,structure and contents of MDA and NOS in cerebral were researched. Results:1.Moisture of cerebal:The brain moisture content of group C was lower than group B,group D,and group E(P＜0.05).There were no significant disparity among group B,group D,and group E.2.The pathological changes through optical microscope: Horizontal cell edema and diastem of circum-micrangium scale-up were found in the group B,group D and group E.Karyopyknosis and rupture of membrane in karyopyknosis were found in group B ande group D.The ischemic edema was significantly lessened in group C.3.Ultramicrostructure changes:The circumstance of pycnosis, chromatin margination,demyelinating and bioblast edema were observed in each of group B,group Dane group E.In the group D, the caryon were lightly anomalism,the heterochromatin was distributed uniformity,and the bioblast was nearly normal.4.Contents of MDA in cerebral:The contents of MDA in cerebra were all increased after separation from DHCA in group B,group C,group D,and group E.The contents of MDA at 2h after undergoing DHCA was the most,and gradually lower then.But at 24h after DHCA,the contents of MDA in group B,group D,group E were also significantly higher than the fake operation group(P＜0.05)In contrast to the group B,contents of MDA reduced significantly in 7-NI group at 2h,6h,12h,24h after separation from DHCA(P＜0.05),and the effect could be kicked back by L-Arg.5.Expression of NOS in cerebral:After experiencing DHCA, the expression of NOS in group B,group C,group D,and group E were all increased.However precondition with 7-NI resulted in a significancant reduction in the expression of NOS at 2h,6h,12h, 24h after separation from DHCA comparing with group B(P＜0.05). The L-Arg could neutralizes the effect of 7-NI and makes the expression of NOS to heighten.Conclusion:1.The mechanism of nerve injury in DHCA was complicated,and NO played very important part in it.2.7-NI had definite protective effects to rat brain in deep hypothermic circulatory arrest,and might be used to prolong safe time of DHCA.3.The effect of 7-NI might be implemented by selective inhibiting nNOS and reduce the generation of NO.4.7-NI could also preserve brain undergoing DHCA by inhibiting the level of MDA.