| Aortic dissection (AD), as a kind of catastrophic disease, is one of the most serious diseases in cardiovascular surgery. The mortality of aortic dissection can be as high as 88% if without of diagnosis and treatment. Stanford type A aortic dissection (AAD) is one of the most critical aortic dissection for wide tearing, multi organ involvement, systemic inflammatory response (SIR) and other reasons.At present, it is still can not be completely cured.if it is not be just in time diagnosis and treatment, from artery dissection happend, the speed of mortality rate will be 1%-2%/per hour increasing. In 1954, Gibbon et al. proposed a new era of cardiovascular surgery with cardiopulmonary bypass (CPB), which provides a new way of thinking for cardiovascular surgery. However, with the fast improvement of science and technology, the researchers found that simple cardiopulmonary bypass technique to deal with the long time intracardiac operation under direct vision can not improve the survival rate, beside it can not solve multiple organ function protection during deep hypothermic circulatory arrest. Postoperative organ protection of the nervous system, respiratory system has become a research hotspot. Thus, deep hypothermic circulation (DHCA) emerges as the times require.Through reducing the body's metabolic rate, let the organs of the body in temporary dormancy state, has reached in finite time of multiple organ protection. At the same time, through different ways of cerebral perfusion methods can effectively reduce postoperative respiratory system and nervous system complications and type A aortic dissection underwent total arch replacement during multiple organ function protection condition. At present, multiple organ protection has become conventional measures during deep hypothermic circulatory arrest.Currently in aortic dissection for deep hpothermia circulatory arrest (DHCA) during the commonly used methods of brain protection mainly includes:according to the blood rheologic:retrograde cerebral perfusion (RCP) and antegrade cerebral perfusion (ACP); according to the insertion site and method:superior vena cava catheterization, right axillary artery or brachiocephalic stem artery catheterization, brachiocephalic artery and left common carotid artery bilateral catheterization, three ways. All of the above are commonly used in clinical brain protection, but in clinical practice, ether of it has advantages and disadvantages. Through summarizing, analyzing and summarizing the clinical data, this study summarizes the advantages and disadvantages of various brain protection methods, and provides the basis and guidance for the selection of individual surgical treatment options.At present, there are many kinds of the animal model of deep hypothermia circulatory arrest.Because of it is time-consuming, expensive, poor reproducibility, and the shortcomings of the experimental animals are easy to die. In our study, through the construction of deep hypothermic cerebral circulation perfusion rat model, we avoided the above defects under the premise can be used to explore different cerebral perfusion.It is a stable animal model can be used in nervous system injury and cerebral protective measures analysis. The results also showed that bilateral cerebral perfusion compared with other cerebral perfusion, has low brain edema and less postoperative neurological dysfunction occurred, is an excellent way of cerebral perfusion witch can be used as a routine deep hypothermia circulatory arrest in cardiovascular surgical operation.Section One The effect of different types of cerebral perfusion in type A aortic dissection.Objective:Analysis the nervous system dysfunction occurrence under different cerebral perfusion of type A aortic dissection (AAD) after total aortic arch replacement. To investigate the clinical effect of different types of cerebral perfusion during DHCA in type A aortic dissection.Methods:Retrospective analysis of 125 cases of Type A Stanford aortic dissection in the Renmin Hospital of Wuhan University from October 2010 to October 2014, clinical data of patients who underwent total arch replacement under deep hypothermia circulatory arrest. According to the different ways of cerebral perfusion, we divided it into 3 groups, group A:107 cases, improved bilateral cerebral antegrade perfusion group, the left common carotid-brachiocephalic stem bilateral catheterization; group B:11 cases, selective unilateral antegrade cerebral perfusion group, the right axillary artery and brachiocephalic stem artery selective unilateral catheterization; group C:7 cases, retrograde cerebral perfusion group of superior vena cava, superior vena cava retrograde catheterization. Analysis the incidence and prognosis of postoperative patients with transient neurological dysfunction (TND), permanent neurological dysfunction (PND).Results:The incidence were significantly increased in group C, compared with group A and group B in transient neurologic dysfunction rate, the gap has statistical significance; There was no significant difference between the rate in incidence of permanent neurological dysfunction; At the same time, at the time of extubation, ICU length of stay, hospitalization time, long-term effect, group A is better than B and C. At the same time, the three groups had no significant difference in cardiopulmonary bypass time, myocardial block time, circulatory arrest time, extubation time and incidence of cerebral vascular accident. In group A, There are 3 cases died, the mortality rate was 2.4%. The postoperative hemiplegia lying in bed for a long time cause a falling product pneumonia and multiple drug resistance in severe infection, eventually because of sepsis, respiratory and circulatory failure leading to death in 1 case; After the withdrawal of the extracorporeal circulation and heparin neutralization by protamine sulfate cause protamine sulfate allergies, resulting in myocardial stunning, postoperative delayed sternal closure to the ICU, but cycle required a lot of vasoactive drugs to maintain, finally circulatory failure leading to death in 1 case. In group A,1 case died in operation, patient with aortic dissection rupture, pericardial tamponade underwent emergency open chest surgery and intraoperative we can see pericardial bloody effusion caused pericardial tamponade, dissection involving the right coronary artery opening and the right atrioventricular groove. At the same time, the aorta and great saphenous vein to the right coronary artery bypass grafting, postoperative end due to low cardiac output, the heart can not be rejumped to death. B, C group no death in this cases.123 patients before discharge review the total aorta CTA (computed tomography angiography), replacement of the aorta were not found in the fistula lumen without distortion, no stenosis of the left subclavian artery CRONUS intraoperative fenestrated endovascular stent without stenosis, left upper limb artery and vertebral artery blood flow was smooth, postoperative patients without limb numbness and other symptoms.96 cases of hard trunk stent distal dissection false lumen closure, visible thrombosis, closure rate was 76.8%. A total of 63 patients were followed up for 3-40 months, cases were reviewed, and 58 cases of false lumen closure were reviewed, the closure rate was 92.1%.Conclusion:Compared with the superior vena cava retrograde cerebral perfusion, antegrade cerebral perfusion can decrease the incidence of transient cerebral dysfunction, which can decrease the incidence of central nervous system dysfunction. Improved bilateral antegrade cerebral perfusion was superior to unilateral antegrade cerebral perfusion in the cooling time and cerebral protective effect. Improved bilateral cerebral perfusion has the advantages of stable cool down temperature and stable rewarming temperature, simple operation, clear operation visual field, less postoperative complications and so on. In the author's view, it is still an effective method to use the superior vena cava retrograde perfusion in patients with large area involving three vessels, especially left and right common carotid arteries. But the effect of cerebral perfusion on one side of the cerebral artery was particularly significant in the patients with unilateral carotid artery occlusion or multiple atherosclerotic plaques.Section two Construction of the rat model of cerebral perfusion with deep hypothermia circulatory arrest.Objective:Currently, many kinds of deep hypothermic cerebral circulation perfusion animal model has established, the main choice of animal model are pigs, dogs, rabbits and other large animals, through the operation of conventional open chest intubation, the cardiopulmonary bypass unit in vitro oxygen combined with simulated deep hypothermic circulatory arrest. But these animal models exist such disadvantage:such as high cost of experiment, operation is relatively complex, operation in experimental animals with high mortality, pipe easy to form thrombus, high requirements of experimental equipment and experimental conditions, put in a lot of manpower resource and time, the disadvantages of poor repeatability, is not suitable for large sample research method. The aim of this study is to find an economical and simple operation, and many repeated tests of deep hypothermic circulatory arrest animal model, through to rats as an animal model to study the deep hypothermic circulatory arrest during brain structure and function change, as an experiments basis for further study of the different cerebral perfusion in deep hypothermic circulation application.Methods:30 rats were divided into normal group, control group and experimental group randomly. In the experimental group, the normal rats were selected and cooled to a temperature of 20 degrees Celsius, the bilateral common carotid arteries were exposed, and the treatment was given. Blocking time with about 40 minutes; the control group was only cool, exposure of bilateral carotid artery treatment, do not clip closed. Dynamic analysis of temperature, blood pressure, heart rate changes in the experimental rats, after 4 hours,12 hours, and 24 hours respectively, evaluate the neurological function rate. Analysis of lactic acid in the blood of jugular vein during operation. After 24 hours, the rats were sacrificed operation to observe the pathological changes of the brain tissue and the content of ATP in rats.Results:the general situation:With deep hypothermia, rat heart rate to 10.6±4.2 /min speed slow down. Experimental group of 1 cases of death in the process of cooling, the operation did not reach the deep low temperature state that there is a cardiac arrest, the temperature is still unable to restore the heart function and circulatory failure and death. Three groups of rats after rewarming and no death. There was no significant difference in cooling and heating time between the three groups, P> 0.05. Neurological rating:By Bederson four scoring evaluation function of nerve injury in rats, the score results after 4 hours is found, the experimental group than in the control group and normal control group were more likely to have temporary neurological dysfunction, but the damage degree are low. At 24 hours after operation, the neurological scores of the three groups were recovered to grade 0. Brain tissue W/D analysis:The experimental group brain water content was significantly increased, there was a significant difference, P<0.05. Pathological microscopic structure:Brain tissue swelling, nerve cell degeneration, electron microscopy, structural damage, nuclear structure disappeared, endoplasmic reticulum, mitochondria swelling. Blood lactic acid content:After 40 minutes of circulatory arrest, the blood lactic acid content in the experimental group was increased significantly compared with normal and control group, P< 0.05. The content of lactic acid in the experimental group decreased gradually, but compared with the other two groups, the difference was still significant, P< 0.05. ATP content:Experimental group of adenosine triphosphate (ATP) content were higher than normal one, which with significant difference (P<0.05); each group compared before and after rewarming, experimental group ATP content in cerebral tissue decreased significantly (P< 0.05).Conclusion:the rat as an animal model, through continuous slow cooling, occlusion of the common carotid artery successfully constructed rat deep hypothermic circulatory arrest model. There were no deaths of this animal model, is a reliable animal model. Deep hypothermic circulation for a long time, easily lead to cerebral edema, accelerate energy metabolism, anaerobic glycolysis induced a large number of generating lactic acid, activation of intracellular enzyme reaction, results in the formation of postoperative neurological dysfunction in varying degrees.Through measures such as dehydration, after 12 hours can recovery from TND.Section three The neuroprotective effect with different cerebral perfusion during deep hypothermic circulatory arrest.Objective:Through rats model of deep hypothermia circulatory arrest with different cerebral perfusion, detecting the NSE level of different time,the expression level of apoptosis related protein Caspase-3,Bcl-2 and Bax, analysis the degree of rat brain injury after operation.Compared different methods of cerebral perfusion in the effect of brain protection. Proposed the safe time of different cerebral perfusion under deep hypothermic circulation.Methods:36 SPF level rats were randomly divided, named as normal one, control and bilateral antegrade cerebral perfusion one and unilateral antegrade cerebral perfusion one, bilateral and unilateral group according to the different time of deep hypothermia were randomly divided into three subgroups. Dynamic analysis of changes in experimental rats in surgery, after surgery in 2h,6h,24h, blood samples were collected and detected the level of serum NSE.24 hours after the operation, the rats were sacrificed and the cell apoptosis were detected by flow cytometry, and by immunohistochemical analysis in cerebral cortex of rats' apoptosis related protein expression level of Caspase-3, Bcl-2 and Bax.Results:(1) Bilateral antegrade cerebral perfusion group compared with unilateral antegrade cerebral perfusion group has light injury of nerve system.With deep hypothermia of 80min, the unilateral antegrade cerebral perfusion group has the highest incidence degree of postoperative dysfunction of rat neural system than other group. (2) 2h after surgery, bilateral antegrade cerebral perfusion group and unilateral antegrade cerebral perfusion group had a rase levels of NSE in serum, but only unilateral antegrade cerebral perfusion group had the highest NSE level significantly, P<0.05. Deep hypothermic 60-80min, bilateral antegrade cerebral perfusion group increased obviously at NSE,40-60min deep hypothermia, single antegrade cerebral perfusion group NSE significantly increased. (3) The results of flow cytometry showed that bilateral antegrade cerebral perfusion has a small number of early apoptotic cells and late apoptosis cells (9.9%), but a large number of apoptotic cells in unilateral antegrade cerebral perfusion after surgery had been shown (29.4%).(4) apoptosis protein immunohistochemistry results showed that Caspase-3 and Bax produced with a high level in unilateral antegrade cerebral perfusion group of cerebral cortex cells, and Bcl-2 in the bilateral antegrade cerebral perfusion group had the highest positive rate,on the other side,unilateral antegrade cerebral perfusion group was the lowest,.It has significant differences with the control one and normal one, P <0.05.Conclusion:The safe time of bilateral antegrade cerebral perfusion is 80min with unilateral antegrade cerebral perfusion for 60min. With a short of deep hypothermic circulatory arrest time, can reduce the level of NSE, has important significance to improve the postoperative recovery of neurological function. Bilateral antegrade cerebral perfusion in the same deep under the condition of low temperature, can effectively inhibit the expression of Caspase-3 and Bax, while promoting the expression of Bcl-2, inhibit the apoptosis and apoptosis associated enzyme reaction process. Under the same depth of low temperature conditions, bilateral antegrade cerebral perfusion can effectively inhibit the expression of Caspase- 3 and Bax, while promoting the expression of Bcl-2, inhibit the apoptosis and apoptosis associated enzyme reaction process. Has a significant neuroprotective effect. |
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