A Study On Brain Protection Of Infants Undergoing Aortic Arch Surgery Based On Different Perfusion Methods

Background One-stage correction for pediatric aortic arch malformation combined with intracardiac lesions is currently the optimal treatment.Standard regional cerebral perfusion(SRCP)or cerebro-myocardial perfusion(CMP)is selectively used in this surgery.Purpose The aim of the study is to compare organ protection efficacy under cerebro-myocardial perfusion and simple regional cerebral perfusion strategies.Methods A retrospective analysis of 284 children who underwent one-stage correction of complex aortic malformations from January 2010 to May 2018 was performed.According to the regional perfusion method,all children were divided into:standard regional cerebral perfusion group(SRCP group,n=202)group and cerebro-myocardial perfusion group(CMP group,n=82).The baseline data were collected and 1:1 propensity score matching(PSM)was performed.Postoperative clinical prognosis was compared with a total of 76 pairs successfully matched.Results Among all patients,the preoperative developmental retardation rate can be as high as 11.6%(33/284),and the pre-term birth rate is 9.2%(26/284).There is no difference in the incidence between the two groups before and after matching.No differences were observed between the two groups regarding preoperative echocardiography,laboratory parameters as well as accompanied intracardiac malformations.After PSM,aortic diagnosis and associated intracardiac anomaly were all comparable.The regional perfusion rate and lowest nasopharyngeal temperature were lower when compared to CMP group(median flow rate and nasopharyngeal temperature were 33.0ml/kg/min vs.45.3ml/kg/min and 26.0? vs 30.6?,respectively,p<0.05),but the rewarming time was significantly extended(p<0.05).Two(2.6%)neurological complications cases happened in the SRCP group,whereas no neurological complications were reported in the CMP group,and the rate was not significantly different(p>0.05).Postoperative wake-up time was comparable between the two groups and delayed wake-up(wake-up time>6 hours)rate was 4.7%(SRCP group,n=3)and 8.6%(CMP group,n=6)respectively with no statistical difference(p=0.50).Myocardial ischemic time was statistically higher in SRCP group,and the median ischemia time in the CMP and SRCP groups were 58.0 and 29.0 minutes,respectively.No significant difference was seen between the two groups in cardiac resumption rate(93.4%vs.92.1%,p=1.00).HTK cardioplegia was more commonly used in the SRCP group(68.4%,n=52,p<0.05).Thirty(39.5%)children in the SRCP group had early-stage cardiac adverse prognostic events(CAPE)with 24(31.6%)in the CMP group(p=0.40).Postoperative mechanical ventilation,ICU stay and postoperative hospital stay were not significantly different between the two groups.In-hospital mortality,delayed chest closure,delayed extubation(>24h),ICU re-entry,and peritoneal dialysis were also comparable between the groups.Conclusions In this on-pump complex aortic arch surgeries cases,standard regional cerebral perfusion and cerebro-myocardial perfusion resulted in similar organ protection effect,as well as the overall short-term prognosis,indicating both perfusion strategies safe and feasible in specific clinical settings.Different perfusion strategies can be chosen according to the characteristics of the children's lesions and the habits of the surgeons clinically.Background Neurological function and learning ability damage after deep hypothermic circulatory arrest(DHCA)is a critical clinical problem.Previous studies have shown that 4-Hydroxynonenal(4-HNE)is a common product after DHCA.The accumulation of such toxic aldehydes during DHCA may cause synaptic plasticity injury,whereas synaptic plasticity is involved in neurological function and learning ability recovery.Activation of ALDH2 enzyme activity can accelerate 4-HNE clearance and prevent synaptic plasticity damage,which may be an important target for brain protection after DHCA.Purpose By establishing a rat DHCA model,the study aims to determine the neuronal damage after DHCA,to confirm the existence of synaptic structure damage,and to demonstrate the neuroprotection effect of ALDH2 enzyme activation.Methods Eighteen SD rats were divided into three groups according to different treatments:Sham group(n=6),DHCA group(n=6),ALDH2 activator(Alda-1)pretreatment&DHCA group(Alda-1 group,n=6).Brain hippocampus was collected and detected about ALDH2 enzyme activity,protein and mRNA expression.Other methods were sequenced used,like Elisa method to detect 4-HNE adduct production,HE staining technique to observe hippocampal neuron morphological changes,TUNEL method to detect apoptotic neurons,transmission electron microscope to observe cell nucleus,synaptic structure and mitochondrial damage,WB and qPCR to detect the expression of synaptic plasticity-related proteins and mRNA,and to detect apoptosis-related proteins and mRNAs as well.Results DHCA hippocampal mitochondrial acetaldehyde dehydrogenase enzyme 2 activity was significantly decreased.After Alda-1 pretreatment,the enzyme activity returned to Sham group level,which was higher than that of DHCA group,and the difference was statistically significant(p<0.05).ALDH2 protein and mRNA expression levels were not different in each group.4-HNE adducts in hippocampal neurons increased significantly in the deep hypothermic circulatory arrest group,and decreased significantly after Alda-1 pretreatment(22.92±9.36 ug)/mg vs 131.69±58.89 ug/mg vs 62.67±28.02 ug/mg,Sham vs DHCA vs Alda-1).TUNEL staining showed that Alda-1 pretreatment can significantly reduce the number of neuronal apoptosis when compared to DHCA group.TEM results indicated that the nucleus and synaptic structure of hippocampal neurons in the DHCA group were damaged;Alda-1 pretreatment could reduce the degree of synaptic structure damage.Synaptic plasticity related protein suggest that Gap43(a synapse-related repair protein)increased significantly in the DHCA group and the Alda-1 group,but the increase in Gap 43 in the Alda-1 group was more significant than that in the DHCA group(p<0.05).The ratio of pp38/p38 was significantly increased in DHCA and in Alda-1 group,and the increase of pp38/p38 was more statistically significant(p<0)in the DHCA group.The Bax/Bcl-2 ratio increased significantly in the DHCA group(p<0.05)as well.Conclusions Alda-1 pretreatment can play a neuroprotective effect in this rat DHCA model.It reduced neuronal apoptosis,and promoted synaptic structure damage recovery.The underlying mechanism may be to activate ALDH2 enzyme activity,increasing toxic aldehydes clearing,thereby reducing pp38-p38 pathway activation caused by DHCA,thus,increasing synaptic structure repair,and reducing DHCA-leading synaptic damage.increasing the expression of synaptic plasticity protein,This research can provide a molecular basis for better neuroprotection in DHCA patients,and lay a solid theoretical foundation for reducing brain complications after DHCA.