| Foreword Characterized by by rapid onset,rapid progression and sudden death,Stanford type A aortic dissection is a kind of cardiovascular disease with high disability and mortality,whose pathological features are large endometrial tears of ascending aorta and distal end.Timely surgical replacement of diseased vessels is the only way to save patients’ lives.Sun’s surgery is the first choice for treatment of type A aortic dissection.However,surgical trauma is very large and surgical mortality and complication rates are still high.Reduction of surgical mortality and complications,promotion of rapid recovery of patients and improvement of postoperative quality of life are the focus of research on aortic dissection.Brain dysfunction is a common complication after surgical treatment,which is mainly manifested as permanent and transient neurological dysfunction,threatening patients’ life,delaying patients’ recovery and reducing patients’ quality of life.Selective cerebral perfusion is an effective method for brain protection during operation of type A aortic dissection.There are still disagreements on the use of this technology,including how to decide whether to conduct anterograde or retrograde cerebral perfusion,unilateral or bilateral cerebral perfusion,selection of perfusion vessels,and control of perfusion flow.The choice of unilateral and bilateral cerebral perfusion is controversial,as they both have advantages and it is difficult to choose.Unilateral perfusion simplifies the operation steps,has little interference to the surgical field,reduces the risk of arterial intubation related embolization,and brain protection effect is recognized.Proponents of bilateral perfusion believe that bilateral perfusion is closer to the physiological state,and the left and right brain perfusion is balanced,free from the influence of Willis’ ring.The safety time of brain hypoperfusion is long,and the brain protection effect is reliable.At present,unilateral perfusion is the first choice for most centers in China.During the operation,intraoperative changes to bilateral perfusion were determined based on the monitoring of cerebral oxygen saturation.Two thirds of doctors in Europe and the United States prefer bilateral perfusion.The advantages and disadvantages of the two methods need to be explored through clinical and experimental research.In this study,aortic dissecting perfusion technology was optimized,that was,bilateral antegrade selective cerebral perfusion,moderate hypothermia and selective perfusion in the lower part of body,comparing with deep hypothermia unilateral cerebral perfusion method.It was found that this optimized arterial perfusion strategy showed advantages in brain protective effect.In order to further explore the mechanism of cerebral perfusion and brain protection of bilateral cerebral perfusion,we designed an animal model,which was a rat model of cerebral hypoperfusion with hypothermia,brain hypoperfusion,low perfusion pressure and blood dilution.The feasibility of this model to evaluate brain cognitive function was tested.With the rat cerebral as the research platform,the cerebral blood flow was recorded by continuous scanning using laser doppler technology,and the dynamic change data of left and right cerebral blood flow under unilateral and bilateral perfusion were obtained.We found that there were differences in cerebral blood flow in different perfusion modes.Motor,sensory and cognitive function tests were performed on rats after cerebral hypoperfusion,and the degree of damage to brain function was found to be different between unilateral and bilateral cerebral perfusion.Based on the above findings,we speculate that: there may be correlation between cerebral perfusion mode,cerebral blood flow and postoperative brain function.Different cerebral perfusion modes lead to different cerebral blood flow states,and the difference of cerebral blood flow state may be the cause of different degrees of brain function injury.Part Ⅰ Optimized selective arterial perfusion approach in total aortic arch replacement of Stanford type A aortic dissectionObjective: To applicate the optimized selective arterial perfusion approach in the total aortic arch replacement of the Stanford A aortic dissection and evaluate its curative effect.Methods: 1.From September 2016 to October 2017,31 cases(25 males and 6 females,aged 50.87±9.08 years)of Stanford A aortic dissection in our hospital performed aortic arch replacement with cardiopulmonary bypass of optimized selective arterial perfusion approach(group O-CPB).The main technical points of the optimized selective arterial perfusion are bilateral antegrade selective cerebral perfusion and moderate hypothermia perfusion in the lower part of body In the early and the same period,60 cases(52 males and 8 females,aged 48.38±12.46 years)performed traditional cardiopulmonary bypass approach(group T-CPB),.2.The perioperative data of the two groups were collected and compared.Multivariate Logistic regression was used to analyze the risk factors for postoperative 30-days mortality.Results: 1.Compared with the group T-CPB,the group O-CPB had a shorter extracorporeal circulation time[(206.90±39.92)min vs(276.37±29.92)min,P<0.001],circulatory arrest time[(5.03±1.54)min vs(21.73±6.67)min,P<0.001] and operation time[(396.68±58.57)min vs(469.28±69.77)min,P<0.001].2.The blood consumption of the group O-CPB was less[(1401±738)m L vs(1705±580)m L,P=0.034].ICU detention time of the group O-CPB was shorter[(5.94±2.45)d vs(7.42±3.53)d,P=0.040],and mechanical ventilation time was shorter[(50.19±37.63)h vs(70.12±40.84)h,P=0.022].3.The postoperative blood lactate concentration[(6.10±3.80)mmol/L vs(8.11±4.51)mmol/L、P=0.037] and C-reactive protein concentration [72.13±22.86)mg/L vs(84.78±17.07)mg/L,P=0.004]of the group O-CPB were lower then the group T-CPB.4.The patients of the group O-CPB were awake earlier than the group T-CPB[(3.32±1.11)h vs(4.14±1.59)h,P=0.013].the absolute value of RASS(Richmond agitation-sedation scale)within 24 hours after surgery of the group O-CPB and the group T-CPB were 1.23±1.06 和 2.15±1.30,respectively,(p=0.001).The incidence of postoperative delirium in group O-CPB and group T-CPB was 35.5% and 48.3%,respectively,(P=0.242).Postoperative delirium duration in group O-CPB was shorter than that in group T-CPB [(4.05±1.94)d vs(5.98±2.73)d,P=0.038]5.There was no statistically significant difference in liver and kidney function protection.Circulatory arrest time and blood consumption were the independent risk factor for the postoperative 30-day mortality of the aortic arch replacement of Stanford A aortic dissection.The 30-day mortality rate of group O-CPB and group T-CPB were 6.5% and 11.7% respectively(P=0.430).Conclusion: 1.The optimized selective arterial perfusion contains three technologies: bilateral antegrade selective cerebral perfusion,moderate hypothermia and selective perfusion in the lower part of body.The perioperative brain protection effect of this technique is superior to that of unilateral cerebral perfusion2.The optimized selective arterial perfusion reduces the operaton injury to blood coagulation and lung function,and reduces the clinical blood consumption,shortens the time of invasive ventilation and ICU detention time,and is beneficial to recovery of the patients;3.The optimized selective arterial perfusion approach can effectively improve the outcome of treatment.for total aortic arch replacement of Stanford type A aortic dissection.Part Ⅱ A rat model for brain protection research with hypothermia and hypoperfusionObjective: To simulate the brain perfusion in aortic dissection operation,an animal model that can be used to evaluate cognitive function was established an experimental animal platform for exploring brain protection methods of aortic dissection operation.Methods: 1.Adult male SD rats(SPF,300-350g)were used in the study.To explore the methods achieving the cerebral perfusion state of hypoperfusion,hypotension,hypothermia and blood dilution.(1)The diameter of common carotid artery was limited to 0.9,0.7 and 0.45 millimeter.The blood flow of common carotid artery was detected by ultrasonic doppler flowmeter,to observe the degree of decreased blood flow.Self-made vascular restrictor was used to control blood flow of common carotid artery in a certain range.(2)Binding different parts of the common carotid artery to observe whether it can reduce the distal blood pressure of the common carotid artery and thereby reduce the cerebral perfusion pressure.(3)By surface cooling,body temperature of rats was reduced to 30℃.Heart rate,blood pressure and blood gas biochemical indexes were observed and recorded before and after temperature drop.(4)Blood dilution is achieved by both bloodletting and fluid infusion.2.To establish and evaluate the rat model of brain hypothermia and hypoperfusion.The rats were divided into two groups: model group and control group.Hypothermia and blood dilution were performed in the model group,.In the control group,anesthesia and operation were the same as that in the model group,but without cooling,blood dilution and cerebral hypoperfusion.The postoperative brain function of the model group and the control group were observed,neurobehavioral tests were performed on the two groups.Results: 1.Limiting the carotid artery diameter can reduce cerebral perfusion.The carotid carotid artery blood flow decreased to 40.17%,74.61% and 88.51% of the original blood flow after the limitation of the total carotid artery diameter of 0.45 mm,0.7mm and 0.9mm..The self-made vascular restrictor can quickly and effectively regulate the blood flow of the common carotid artery.2.The discontinuous binding method can gradually reduce the blood pressure of the distal carotid artery.After one,two and three times binding,blood pressure decreased by 35.11%,45.39% and 51.25%,respectively.3.The body surface induced hypothermia could control the body temperature in the set range,and the rats showed metabolic acidosis after hypothermia and could recover.4.Method of bloodletting and fluid infusion can achieve blood dilution.After 3ml,6ml and 9ml of blood were drawn,the hematokrit in the rats decreased to 84.34%,73.83% and 62.66% of the rats before bloodletting.and bloodletting of 6ml is relatively effective and safe.5.There were no deaths in the two groups.The rats in the model group sustained brain hypothermia and hypoperfusion for 30 minutes,followed by cyclic changes of decreased heart rate and blood pressure,metabolic acidosis.The rats could recovered after blood transfusion,rewarming and acid treatment.6.Neurobehavioral test can be completed after operation.The test results showed that the rats in the model group had no symmetry deviation in movement and sensation.In the shuttle box experiment,the active avoidance rate in the control group did not decrease after surgery.The rats in the model group showed a significant decrease in the active avoidance rate after operation[(65.83±8.61)% vs(86.67±8.16)%,P=0.005].The water maze experiment showed that the test parameters of the control group did not decrease.The time ratio of the right area to search for the target decreased after operation in the model group[(31.50±5.24)% vs(43.33±10.27)%,P=0.030].The rats were less likely to find the target correctly[(2.33±1.03)次 vs(4.33±1.86)%,P=0.018].The learning and memory ability of the rats in the model group was significantly reduced,suggesting that the hypoperfusion surgery caused cognitive function impairment in the rats.Conclusion: 1.The cerebral hypothermia and hypoperfusion model of rat is simple to operate and has a high success rate,which can simulate the cerebral perfusion status of hypothermia,low flow rate,low perfusion pressure and blood dilution during aortic dissection.This animal model can be used to evaluate brain cognitive function.It is named as off-bypass cerebral hypothermia and hypoperfusion rat model.2.Due to the absence of extracorporeal circulation,the application range of the off-bypass cerebral hypothermia and hypoperfusion rat model is limited,which is applicable to the early exploration stage of cerebral hypoperfusion in aortic dissection.3.For the characteristics of simple operation,less resource consumption and stability,the cerebral hypothermia and hypoperfusion model of rat is an alternative brain function protection study animal modelPart Ⅲ Effects of unilateral and bilateral antegrade cerebral perfusion on brain blood flow and brain function in ratsObjective: Using the off-bypass cerebral hypothermia and hypoperfusion rat model,to observe the cerebral blood flow pattern under unilateral and bilateral cerebral perfusion,and evaluate the effects of two perfusion modes on brain function.Methods: 1.To observe the changes of cerebral blood flow and brain tissue morphology under unilateral and bilateral cerebral perfusion.In the U_flow group,the left common carotid artery was blocked,the right common carotid artery was reduced to 4ml/min,and the cerebral hypoperfusion lasted for 46 minutes.In the B_flow group,the blood flow of the left and right common carotid artery was limited to fixed low flow of 4ml/min,and the cerebral hypoperfusion lasted for 46 minutes.Rats were sacrificed 24 hours after surgery and brain tissue was taken out for morphological examination.2.To observe the neurobehavioral changes of rats after unilateral and bilateral cerebral perfusion.Twenty-four adult male SD rats(SPF)were randomly divided into two groups(n=12),unilateral cerebral perfusion group for ethology(U_eth group)and bilateral cerebral perfusion group for ethology(B_eth group).The surgical method was the same as the first part.Blood samples were collected for testing the serum concentrations of S100β and neuron-specific enolase(NSE).Postoperative the elevated body swing test and the bilateral tactile stimulation test were performed to evaluate the symmetry of movement and sensation of the rats,and the shuttle box and water maze test were performed to compare the cognitive functions of the two groups of rats.Results: 1.Both the U_flow group and the B_flow group showed a significant decrease in cerebral blood flow after the start of low perfusion.In the U_flow group,the left cerebral blood flow of was lower than that of the right brain,and the difference was statistically significant.The B_flow group showed no significant difference in left and right cerebral blood flow.2.The left and right cerebral blood flow of both the U_flow group and the B_flow group showed a fluctuating state.The fluctuation amplitude of the cerebral blood flow of the U_flow group was greater than that of the B_flow group,and the difference was statistically significant.3.Under the optical microscope(x 400),there were no large areas of necrosis in brain tissue of both groups.the brain tissue of both groups showed edema,with a few scattered necrotic neurons.4.The serum NSE concentration of the U_eth group was higher than that of the B_eth group [(387.71±37.37)ug/L vs(352.27±40.88)ug/L,P=0.037].5.There was no difference in motor sensory symmetry and cognitive function between the U_eth group and the B_eth group before surgery.After surgery,in the shuttle box experiment,the active avoidance rate of the B_eth group was higher than that of the U_eth group[(61.25±8.56)% vs(52.5±10.98)%,P=0.040].In Morris water maze test,the rats in U_eth group had longer escape latency than the B_eth group[(79.92±9.70)sec vs(71.17±10.07)sec、(75.72±10.15)sec vs(66.22±9.97) sec、(70.31±9.70)sec vs(60.42±6.17)sec,P=0.001],and shorter search time in the correct target area than the B_eth group[(30.67±5.14)% vs(35.67±4.12)%,P=0.015]。There was no significant difference between the two groups in the number of passes through the target.Combined the results of the shuttle box and water maze experiment suggested that the degree of cognitive function injury in U_eth group was heavier than that in B_eth group after surgery.Conclusion: 1.The left and right cerebral blood flow was unbalanced with unilateral cerebral perfusion.The left and right cerebral blood flow is roughly balanced by bilateral cerebral perfusion.2.The blood flow in brain tissue area fluctuates unevenly.Compared with bilateral cerebral perfusion,the amplitude of blood flow fluctuation in brain area of unilateral cerebral perfusion was greater,and the imbalance of regional blood supply was more obvious.3.Compared with bilateral cerebral perfusion,unilateral cerebral perfusion is more severe in brain damage and cognitive dysfunction is more obvious.4.There may be correlation between cerebral perfusion mode,cerebral blood flow and brain function.The cerebral perfusion mode affects the cerebral blood flow,and the difference of the cerebral blood flow may be the cause of different degrees of brain injury.The more severe brain damage caused by unilateral cerebral perfusion may be related to the larger amplitude of imbalance fluctuations of blood flow in brain regions.Summary In our clinical study,we found that unilateral perfusion and bilateral perfusion showed differences in postoperative consciousness recovery and cognitive function of patients.In order to further explore its mechanism,relevant basic experimental studies were conducted.We designed and produced a new animal model of cerebral hypoperfusion,which has the characteristics of simplicity,economy and stability,can evaluate brain cognitive function,and provides a new platform for research on brain protection of main artery dissection.Using this model,we analyzed the mechanism of brain injury under hypoperfusion from the perspective of cerebral blood flow changes.By observing the dynamic changes of cerebral blood flow,we found possible correlation between cerebral perfusion mode,cerebral blood flow state and brain function.The cerebral perfusion mode affects the cerebral blood flow,and the difference of the cerebral blood flow may be the cause of different degrees of brain injury.This finding provides a new view and pointcut to study the protective effect of brain perfusion in main artery dissection. |
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