Objective To observe the influence of edaravone perfusion via the pulmonary artery on postoperative lung tissue and lung function during pulmonary ischemia in deep hypothermic circulatory arrest （DHCA）， and explore its possible mechanism. Methods A total of 24 healthy New Zealand white big-ear rabbits were randomly divided into three groups： （1） control group： DHCA model under cardiopulmonary bypass （CPB） was established； （2）low potassium dextran （LPD）group： LPD solution perfusion via the pulmonary artery after the establishment of DHCA； （3）edaravone group：LPD solution containing edaravone （5 mg/kg） perfusion via the pulmonary artery after the establishment of DHCA. Oxygenation index and lung compliance were observed at the time of baseline condition， recovery of ventilation， 1 hour and 2 hours after recovery of ventilation， and postoperative lung function of the three groups were compared. Malondialdehyde （MDA） and superoxide dismutase （SOD） in pulmonary venous blood were measured. All the rabbits were sacrificed after the operation. HE staining and immunohistochemistry were performed on the lung tissues to investigate lung structure changes and inflammatory reaction. Transmission electron microscopy was used to compare ultrastructural changes of lung.Results There were no statistical difference in oxygenation index， lung compliance， MDA and SOD among the 3 groups under the baseline condition （P＞0.05）. After recovery of ventilation， oxygenation index and lung compliance deteriorated to varying degrees in all 3 groups. Oxygenation index and lung compliance of the control group and LPD group at the time of recovery of ventilation， 1 hour and 2 hours after recovery of ventilation were significantly lower than those of edaravone group （oxygenation index：recovery of ventilation and in control group and edaravone group: 198.25±11.02 mm Hg vs. 244.87±13.05 mm Hg；lung compliance：one hour after recovery ventilation in control group and edaravone group：45.88±1.64 ml/cm H2O vs. 59.75±2.38 ml/cm H2O；P＜0.05）. After CPB removal， MDA levels were increased to varying degrees in all 3 groups. MDA levels of the control group and LPD group at the time of CPB removal， 1 hour and 2 hours after CPB removal were significantly higher than those of edaravone group （P＜0.05）. After CPB removal， SOD levels were decreased to varying degrees in all 3 groups. SOD levels of the control group and LPD group at the time of CPB removal， 1 hour and 2 hours after CPB removal were significantly lower than those of edaravone group （P＜0.05）. HE staining showed clear lung structure， less red blood cell leakage， less inflammatory cell infiltration， and less alveolar fluid accumulation in the edaravone group. Immunohistochemistry showed that integral light density of interleukin 6 （IL-6）in edaravone group was significantly lower than those of the LPD group and control group （14.44±1.75 vs. 20.18±2.22， P＜0.05）. Transmission electron microscopy showed integral basement membrane structure， clear blood gas barrier structure， significantly larger number of type II epithelial cells， abundant but not swollen mitochondria and lamellar bodies in the cytoplasm in the edaravone group， which were destroyed in varying degrees in the LPD group and control group. Conclusion Pulmonary artery perfusion of protective solution in low temperature can significantly reduce lung injury induced by DHCA and CPB. Protective solution containing edaravone in low temperature can better decrease lung injury and protect oxygenation.
To valuate cerebral protection by retrograde cerebral perfusion (RCP) via superior vena cava,the study results for the last ten years have been reviewed.RCP is regarded as an assistant method in deep hypothermic circulatory arrest(DHCA) in that it provides partial brain blood flow,maintains a low brain temperature,optimizes cerebral metabolic function during DHCA by supplying oxygen and some nutrient and removal of catabolic products;it also reduces the incidence of cerebral embolization by flushing out air...
Objective To investigate different gases and hematocrits on cerebral injury during deep hypothermic circulatory arrest (DHCA) in a piglet model including monitoring by near-infrared spectroscopy (NIRS). Methods Twenty-four piglets were assigned to 4 groups with respect to different blood gas and hematocrit during DHCA. Group A: hematocrit was maintained between 0.25 to 0.30, pH-stat strategy during cooling phases and alpha stat strategy in other phases; group B: hematocrit was maintained between 0.25 to 0.30 and alpha stat strategy; group C: hematocrit was maintained between 0.20 to 0.25, pH-stat strategy during cooling phases and alpha stat strategy in other phases; group D: hematocrit was maintained between 0.20 to 0.25 and alpha stat strategy. Cerebral oxygenations of piglets were monitored continuously by NIRS. The brain was fixed in situ at 6 hours after operation and a histological score for neurological injury was assessed. Results Oxygenated hemoglobin (HbO2) and total hemoglobin (HbT) signals detected by NIRS were significantly lower in group D than those in group A and group B during cooling (Plt;0.05). Oxygenated hemoglobin nadir time was significantly shorter in group A(Plt;0.05). All piglets with oxygenated hemoglobin signal nadir time less than 25 minutes were free from histological evidence of brain injury. Conclusion Combination of pH-stat strategy and higher hematocrit reduces neurological injury after DHCA.
ObjectiveTo investigate the impact of deep hypothermic circulatory arrest (DHCA) with antegrade cerebral perfusion (ACP) on cognitive function of patients undergoing surgical therapy for acute Stanford type A aortic dissection (AD). MethodsBetween January 2009 and March 2012, 48 patients with acute Stanford type A AD underwent Sun's procedure (aortic arch replacement combined with stented elephant trunk implantation) under DHCA with ACP in Nanjing Hospital affiliated to Nanjing Medical University. There were 40 males and 8 females with their age of 51.3±13.6 years. Circulatory arrest time and time for postoperative consciousness recovery were recorded. Preoperative and postoperative cognitive functions of each patient were evaluated by mini-mental status examination (MMSE). ResultsMean cardiopulmonary bypass time of the 48 patients was 237.3±58.5 minutes, and mean circulatory arrest time was 37.3 ±6.9 minutes. Four patients died postoperatively with the causes of death including lung infection, multiple organ dysfunction syndrome, myocardial infarction and acute respiratory distress syndrome. Forty-one patients recovered their consciousness within 24 hours postoperatively, and the mean time for postoperative consciousness recovery was 15.3±6.5 hours. Preoperative MMSE score was 28.6±1.1 points, and MMSE score at 1 week postoperatively was 23.6±4.5 points. Thirty-one patients were followed up for 6 months with the follow-up rate of 70.45%. The average MMSE score of the 31 patients at 6 months after surgery was 27.6±2.1 points which was significantly higher than postoperative average MMSE score (P < 0.05), but not statistically different from preoperative average MMSE score (P > 0.05). ConclusionsDHCA with ACP can provide satisfactory cerebral protection for patients undergoing surgical therapy for acute Stanford type A AD, but patients' cognitive function may be adversely affected in the short term. As long as cerebral infarction or hemorrhage is excluded in CT scan of the brain, such adverse impact may generally disappear automatically within 6 months after surgery.
Abstract： Objective To investigating the variance of nuclear factorkappa B（NF-κB）,inflammatory factor and polymorphonuclear cells(PMNs) in lung， our study infer the role of PMNs infiltration and early activity of NF-κB in empirical study of lung injury in deep hypothermia and circulatory arrest. Our study also guess the possible mechanism of action in order to provide a more excellent program for lung protection. Methods Twelve immature pigs were randomly divided into two groups，there are six pigs in each group，one group was normothermic parallel circulation(control group)，the other was deep hypothermia and circulatory arrest(DHCA, experimental group)，we obtain lung tissue and venous blood from pigs to measure the variances of NF-κB by immunohistochemistry and inflammatory factor by enzymelinked immunosorbent assay(ELISA) at different time. Results The expression of NF-κB of the lung tissue specimen was negative before parallel circulation in both groups, there was no brown dyed cell nucleus and the variation was no statistically difference in two groups. The expression of NF-κB reached it‘s peak at half an hour of ischemia reperfusion, and most of the brown dyed cell nucleus were PMNs, then the expression of NF-κB decreased in the experimental group. The lung tissue specimens were all weakly negative at the time points after parallel circulation and there was no statistical difference among them. But the content of inflammatory factor increased gradually from half an hour of ischemia reperfusion to two hour of ischemia reperfusion， which reached their peak at two hour of ischemia reperfusion.There was significance variances at the content of tumor necrosis factor-α(TNF-α) at one hour of ischemia reperfusion， while at one and a half hour of ischemia reperfusion. There was significance variance at the content of interleukin-8 and interleukin-6 in the experimental group. While in the control group, there was statistically difference before and after parallel circulation, but there was no statistically difference among the time points after parallel circulation. Conclusion The early activity of NF-κB may have an important role in lung injury of DHCA，treatments aim directly at NF-κB may provide an important strategy for lung injury of DHCA.
Objective To determine risk factors of delayed recovery of consciousness after aortic arch surgery underdeep hypothermic circulatory arrest （DHCA） and antegrade selective cerebral perfusion （ASCP）. Methods We retrospectively analyzed clinical data of 113 patients who underwent aortic arch surgery under DHCA＋ASCP in the Affiliated Drum Tower Hospital， Medical School of Nanjing University from October 2004 to April 2012. According to whether they regained consciousness within 24 hours after surgery， all the 113 patients were divided into normal group （73 patients including 55 males and 18 females with their average age of 48.1±10.9 years） and delayed recovery group （40 patients including 29 males and 11 females with their average age of 52.2±11.4 years）. Risk factors of delayed recovery of consciousness after surgery were evaluated by univariate analysis and multivariate logistic regression analysis. Results Nine patients （8.0%） died postoperatively， including 5 patients with multi-organ failure， 2 patients with heart failure， 1 patient with mediastinal infection， and 1 patient with pulmonary hemorrhage. There were 7 deaths （17.5%） in the delayed recovery group and 2 deaths （2.7%） in the normal group， and the in-hospital mortality of the delayed recovery group was significantly higher than that of the normal group （P=0.016）. A total of 94 patients （including 65 patients in the normal group and 29 patients in the delayed recovery group） were followed up for 4-95 months. Eight patients （including 5 patients in the normal group and 3 patients in the delayed recovery group） died during follow-up， including 2 patients with stroke， 3 patients with heart failure， 2 patients with pulmonary hemorrhage and 1 patient with unknown cause. Ten patients were lost during follow-up. Univariate analysis showed that age （P=0.042）， hypertension （P=0.017）， emergency surgery （P=0.001）， cardiopu- lmonary bypass （CPB） time （P=0.007）， aortic cross-clamp time （P=0.021）， and blood transfusion（P=0.012）were risk factors of delayed recovery of consciousness after aortic arch surgery. Multivariate logistic regression showed that emergency surgery （P=0.005） and CPB time＞240 minutes （P=0.000） were independent risk factors of delayed recovery of consciousness after aortic arch surgery. Conclusion Delayed recovery of consciousness after aortic arch surgery is attributed to a combination of many risk factors. Correct patient diagnosis， lesion site and involved scope should be made clear preoperatively in order to choose appropriate surgical strategies. During the surgery， strengthened brain protection， shortened operation time， improved surgical techniques， and perioperative stable circulation maintenance are all important measures to prevent delayed recovery of consciousness after aortic arch surgery.
ObjectiveTo establish a novel animal model of deep hypothermic circulatory arrest (DHCT) in rabbits without thoracotomy, and investigate acute kidney injury (AKI) induced by DHCT and early novel biomarkers of AKI. MethodsForty-two New Zealand big ear rabbits (3.5-4.0 kg, male or female) were randomly divided into 2 groups with 21 rabbits in each group. Cardiopulmonary bypass (CPB) was established via the right carotid artery and jugular vein in both groups. In Group A, CPB continued when the rectal temperature was maintained at 28℃. In group B, DHCT started when the rectal temperature reached 16℃ to 18℃ and lasted for 60 minutes before CPB was resumed and rewarming was started. The rectal temperature was restored to 35℃ within 30 minutes, then CPB was maintained for 30 minutes. CPB time was same in both groups. Preoperatively and 6 hours, 24 hours and 48 hours after the operation, venous blood samples were taken to examine serum creatinine (Cr) and β-trace protein (β-TP), and urine samples were taken to examine neutrophil gelatinase-associated lipocalin (NGAL). Four rabbits were sacrificed at respective above time points to measure renal malondialdehyde (MDA) content. Hematoxylin-Eosin (HE) staining, TUNEL assay and transmission electron microscopy were used to examine morphological changes of renal tubular epithelial cells (TECs). ResultsFour rabbits died in group A and five rabbits died in Group B during the experiment.(1)Blood Cr:There was no statistical difference between different time points in Group A (P > 0.05). In Group B, serum Cr at 24 hours after the operation was significantly higher than other time points, and also significantly higher than that of group A (P < 0.05).(2)Blood β-TP and urinary NGAL:There was no statistical difference between different time points in Group A (P > 0.05). In Group B, blood β-TP and urinary NGAL at the time of 6 hours, 24 hours and 48 hours postoperatively were significantly higher than preoperative levels (P < 0.05). Blood β-TP and urinary NGAL at the time of 24 hours postoperatively were significantly higher than other time points (P < 0.05). Blood β-TP and urinary NGAL at the time of 6 hours, 24 hours and 48 hours postoperatively were significantly higher than those of group A (P < 0.05).(3)Renal MDA content of Group B at the time of 24 hours postoperatively was significantly higher than other time points as well as that of Group A (P < 0.05).(4) HE staining showed serious pathological injuries of renal TECs at the time of 24 hours postoperatively in Group B. There was no significant pathological injury of renal TECs at the time of 24 hours postoperatively in Group A. (5)TUNEL-positive rate of group B at the time of 24 hours postoperatively was significantly higher than other time points as well as that of group A (P < 0.05).(6)Transmission electron microscope showed serious pathological injuries of renal TECs organelles at the time of 24 hours postoperatively in Group B. There was no significant pathological injury of renal TECs organelles in Group A. ConclusionsThis DHCT rabbit model without thoracotomy is a simple, convenient, and economical animal model with long-term animal survival for the study of DHCT-induced organ injury. AKI is most serious at the time of 24 hours after DHCA. Blood β-TP and urinary NGAL can be used as early biomarkers of DHCT-induced AKI.
Objective Through establishment of brain slice model in rats with perfusion and oxygen glucose deprivation (OGD), we investigated whether this model can replicate the pathophysiology of brain injury in cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) or not and whether perfusion and OGD can induce preoligodendrocytes (preOL) injury or not, to provide cytological evidence for white matter injury after cardiopulmonary bypass. Methods Three to five living brain slices were randomly obtained from each of forty seven-day-old (P7) Sprague-Dawley (SD) rats with a mean weight of 14.7±1.5 g. Brain slices were randomly divided into five groups with 24 slices in each group: control group with normothermic artificial cerebralspinal fluid (aCSF) perfusion (36℃) and DHCA groups: OGD at 15℃, 25℃, 32℃ and 36℃. The perfusion system was established, and the whole process of CPB and DHCA in cardiac surgery was simulated. The degree of oligodendrocyte injury was evaluated by MBP and O4 antibody via application of immunohistochemistry. Results In the OGD group, the mature oligodendrocytes (MBP-positive) cells were significantly damaged, their morphology was greatly changed and fluorescence expression was significantly reduced. The higher the OGD temperature was, the more serious the damage was; preOL (O4-positive) cells showed different levels of fluorescence expression reduce in 36℃, 32℃ and 25℃ groups, and the higher the OGD temperature was, the more obvious decrease in fluorescence expression was. There was no statistically significant difference in the O4-positive cells between the control group and the 15℃ OGD group. Conclusion The perfused brain slice model is effective to replicate the pathophysiology of brain injury in CPB/DHCA which can induce preOL damage that is in critical development stages of oligodendrocyte cell line, and reduce differentiation of oligodendrocyte cells and eventually leads to hypomyelination as well as cerebral white matter injury.