Application of cerebral-myocardial perfusion combined with lower body circulatory arrest in pediatric complex aortic arch surgery

Background Adjunct RCP to DHCA ensures some extent uninterrupted cerebral perfusion and that promotes one-stage repair of complex aortic arch anomaly.One-stage repair may induce longer myocardial ischemic time.So there evolved cerebral-myocardial perfusion to reduce myocardial ischemic time.Methods We reviewed 78 patients from January 2010 to July 2017 in our center.

Perioperative outcomes of different temperature management in pediatric aortic arch surgery:a single center 8-year experience

Objective With the widespread application of regional low flow perfusion, deep hypothermia is non-essential for organ protection;therefore, there is a growing tendency to increase systemic temperature.

Effect of pulsatile perfusion during cardiopulmonary bypass in terms of radial artery sphygmogram

OBJECTIVE: To investigate a quantitative method for using radial artery pulse waveforms to assess the effect of pulsatile flow during cardiopulmonary bypass(CPB).METHODS: A total of 34 adults with heart disease who underwent open-heart surgery between April2010 and January 2011 were randomized into a pulsatile perfusion group(n=17) and a non-pulsatile perfusion group(n=17). Radial arterial pulse waveforms of pulsatile and non-pulsatile perfusion patients were observed and compared before and during CPB.RESULTS: No pulse waveform could be detected at patients' radial artery in both groups when the aorta was cross-clamped. Pulse waveforms could be detected at pulsatile perfusion patients' radial artery, but could not be detected at non-pulsatile perfusion patients' radial artery during CPB. Additionally, patients' pulse waveforms during pulsatile perfusion were lower than those before the operation.CONCLUSION: Our findings indicate that radial artery sphygmogram can be used as a valid indicator to evaluate the effectiveness of pulsatile perfusion during CPB.

Genetically predicted waist circumference and risk of atrial fibrillation

Introduction:Observational studies have revealed an association between waist circumference(WC)and atrial fibrillation(AF).However,it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors.Therefore,the causal role of WC in AF is unclear.This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization(MR)analysis.Methods:In our two-sample MR analysis,the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study(GWAS)of WC(42 single nucleotide polymorphisms with a genetic significance of P<5×10^(-8)).The data of WC(from the Genetic Investigation of ANthropometric Traits consortium,containing 232,101 participants)and the data of AF(from the European Bioinformatics Institute database,containing 55,114 AF cases and 482,295 controls)were used to assess the causal role of WC on AF.Three different approaches(inverse variance weighted[IVW],MR-Egger,and weighted median regression)were used to ensure that our results more reliable.Results:All three MR analyses provided evidence of a positive causal association between high WC and AF.High WC was suggested to increase the risk of AF based on the IVW method(odds ratio[OR]=1.43,95%confidence interval[CI],1.30-1.58,P=2.51×10^(-13)).The results of MR-Egger and weighted median regression exhibited similar trends(MR-Egger OR=1.40[95%CI,1.08-1.81],P=1.61×10^(-2);weighted median OR=1.39[95%CI,1.21-1.61],P=1.62×10^(-6)).MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF.Conclusions:Our findings suggest that greater WC is associated with an increased risk of AF.Taking measures to reduce WC may help prevent the occurrence of AF.

Pulmonary artery perfusion with HTK solution prevents lung njury in infants after cardiopulmonary bypass

Background Pulmonary artery perfusion during cardiopulmonary bypass （CPB） is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension. Methods Between June 2009 and December 2009, 24 consecutive infants with congenital heart defects and pulmonary hypertension were randomly divided into perfused group （n=12） and control group （n=-12）. Oxygen index, alveolar-arterial 02 gradient, serum levels of malondialchehyche （MDA）, interleukin （IL）-6, -8, -10, soluble intercellular adhesion molecule-1 （slCAM-1）, and P-seiectin were measured before commencement and serially for 48 hours after termination of bypass. Results Oxygenation values were better preserved in the perfused group than in the control group. The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB, but it was restored faster and earlier in the perfused group. The serum levels of IL-8, slCAMol, and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group, except for slCAM-1 The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups, but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB. The serum P-selectin levels in the control group immediately after CPB were significantly higher than prebypass levels. Moreover, there were no significant differences in postoperative clinical characters, except for the intubated time. Conclusion In infants with congenital heart defects, pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response.

Passive graft perfusion in off-pump coronary artery bypass grafting

Background Myocardial protection during off-pump coronary artery bypass grafting （OPCABG） is a multifactorial problem in which maintaining stable systemic hemodynamics is very important. In this study passive graft perfusion （PGP） was applied to investigate the effect during and after OPCABG as evaluated by cardiac troponin I （CTnl） and hemodynamic indexes. Methods Thirty first-time patients underwent OPCABG under one surgeon. They were randomly divided into two groups： The passive graft perfusion group （PGP, n=15） received distal coronary perfusion during the anastomosis and immediate graft perfusion after the distal anastomosis. The control group, no graft perfusion group, （NGP, n=15） received no graft perfusion after the distal anastomosis. The results of the two protocols were evaluated by concentration of CTnl and hemodynamic indexes before induction and after operation. Results There were no statistically significant differences between these two groups in their perioperation parameters. The level of CTnl increased postoperatively, reached its peak at 6 hours （P〈0.05） and recovered by the 6 days postoperative. Compared with the control group the concentration of CTnl in the PGP group was significantly lower at 6 and 24 hours （P〈0.01）. Compared with the NGP group, cardiac index （CI） in the PGP group was higher at 12 and 24 hours after operation （P〈0.05）. The period of mechanical ventilation was significantly shorter in the PGP group than in the NGP group （P〈0.05）. Conclusion PGP can increase the flow to the myocardium and shorten the heart ischemia time, thus maintain stable systemic hemodynamics, supply a satisfactory CI after surgery and improve surgery outcome.

A Novel Perspective on Histopathology Provides Novel Insights into Surgical Effects in Pulmonary Atresia,Ventricular Septal Defect,and Major Aortopulmonary Collateral Arteries:A Case-Series Study

Background:Never had literatures characterized the relationship between the property of major aortopulmonary collateral arteries(MAPCAs)and outcomes of selective unifocalization of pulmonary atresia with ventricular septal defects and MAPCAs.Methods:This is a case-series study.Thirteen patients were included.Angiographybased assessment was conducted to determine whether collateral arteries should be unifocalized or treated with intraoperative ligature.Specimens were collected and stained by HE and ET+VG.Results:Twelve patients underwent one-stage unifocalization at a median age of 37 months(range:6–228 months)and a median weight of 14.0 kg(range:5.0–49.0 kg),which produced a favorable right ventricle to aortic systolic pressure ratio of no more than 0.5 except in one patient who died.Patients were divided into three groups:Group 1(n=6),had no native pulmonary arteries,and collateral arteries supplied all pulmonary blood;Group 2(n=6)presented dysplastic native pulmonary arteries on one or both sides,and in some lung lobes or segments,blood was supplied only by collateral arteries;Group 3(n=1)had well-developed left and right pulmonary arteries,and collateral arteries,and pulmonary arteries provided blood flow to the same segments.Pathological reports demonstrated two types of collateral arteries:Elastic arteries presented an arborization distribution similar to native pulmonary artery walls,while muscular arteries showed high resistance and distortion.We selectively unifocalized single-supply collateral arteries with morphologic features based on the arborization distribution.Conclusions:We found that there were two kinds of MAPCAs with different histology,and we performed selective UF for MAPCAs that might belong to the elastic artery.Selective unifocalization achieved a low right ventricle to aortic systolic pressure ratio and favorable surgical effects.

Expert consensus on the use of human serum albumin in adult cardiac surgery

Introduction Albumin,which is a 65-kDa liver-synthesized protein,accounts for nearly 50%of total plasma protein and contributes to approximately 80%of intravascular oncotic pressure.Albumin helps maintain microvascular integrity,functions as an antioxidant,and transports hormones,fatty acid,bile salts,bilirubin,electrolytes(e.g.,calcium,magnesium,copper,zinc,et al.),and drugs.[1–3]Human serum albumin(HSA)is a sterile,liquid albumin product derived from large pools of human plasma by fractionation and pasteurization.The medical use of HAS could date back to approximately the time of World War II.

Cerebral Metabolic Profiling of Hypothermic Circulatory Arrest with and Without Antegrade Selective Cerebral Perfusion： Evidence from Nontargeted Tissue Metabolomics in a Rabbit Model

Background： Antegrade selective cerebral perfusion （ASCP） is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest （DHCA）. However, brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology. Methods： To clarify the metabolomics profiling of ASCP, 12 New Zealand white rabbits were randomly assigned into 60 min DHCA with （DHCA＋ASCP [DA] group, n = 6） and without （ DHCA [D] group, n = 6） ASCP according to the random number table. ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery. Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass. The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry. Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites, and then Student＇s t-test was applied to test for statistical significance between the two groups. Results： Metabolic profiling of brain was distinctive significantly between the two groups （Q2y = 0.88 for partial least squares-DA model）. In comparing to group D, 62 definable metabolites were varied significantly after ASCP, which were mainly related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway, subdued anaerobic metabolism, and oxidative stress. In addition, L-kynurenine （P = 0.0019）, 5-methoxyindole-3-acetic acid （P = 0.0499）, and 5-hydroxyindole-3-acetic acid （P = 0.0495） in tryptophan metabolism pathways were decreased, and citrulline （P - 0.0158） in urea cycle was increased in group DA comparing to group D. Conclusions： The present study applied metabolomics analysis to identify the cerebral metabolic profiling in rabbits with ASCP, and the results may shed new lights that cerebral metabolism is better preserved by ASCP compared with DHCA alone.

The cardiovascular protective effect and mechanism of calycosin and its derivatives

Cardiovascular disease is the main cause of mortality and morbidity in the world,especially in developing countries.Drug therapy is one of the main ways to treat cardiovascular diseases.Among them,great progress has been made in the treatment of cardiovascular diseases with traditional Chinese medicine.In terms of experimental research,the mechanism of traditional Chinese medicine in the treatment of cardiovascular diseases has been thoroughly discussed in vitro and in vivo.In terms of clinical treatment,traditional Chinese medicine with flavonoids,saponins and alkaloids as the main effective components has a definite effect on the treatment of cardiovascular diseases such as arrhythmia,myocardial ischemia,angina pectoris and myocardial infarction,with high safety and good application prospects.With the further research on the effective ingredients,mechanism and adverse reactions of traditional Chinese medicine,it will be beneficial to the effectiveness of traditional Chinese medicine,reduce side effects and promote the modernization of traditional Chinese medicine.Calycosin and its derivatives,the main bioactive flavonoids in Astragalus membranaceus have multiple biological effects,such as antioxidant,pro-angiogenesis,anti-tumour,and anti-inflammatory effects.Based on the above biological effects,calycosin has been shown to have good potential for cardiovascular protection.The potent antioxidant effect of calycosin may play an important role in the cardiovascular protective potential.For injured cardiac myocytes,calycosin and its derivatives can alleviate the cell damage mainly marked by the release of myocardial enzymes and reduce the death level of cardiac myocytes mainly characterized by apoptosis through various mechanisms.For vascular endothelial cells,calycosin also has multiple effects and multiple mechanisms,such as promoting vascular endothelial cell proliferation,exerting vasodilating effect and directly affecting the synthesis function of endothelial cells.The present review will address the bioactivity of calycosin in cardiovascular diseases such as protective effects on cardiac myocytes and vascular endothelial cells and elucidate main mechanism of calycosin and its derivatives to exert the above biological effects.

A novel and feasible way to cultivate and purify endothelial progenitor cells from bone marrow of children with congenital heart diseases

Background Endothelial progenitor cells （EPCs） are used in vascular tissue engineering and clinic therapy. Some investigators get EPCs from the peripheral blood for clinic treatment, but the number of EPCs is seldom enough. We have developed the cultivation and purification of EPCs from the bone marrow of children with congenital heart disease, to provide enough seed cells for a small calibre vascular tissue engineering study. Methods The 0.5-ml of bone marrow was separated from the sternum bone, and 5-ml of peripheral blood was collected from children with congenital heart diseases who had undergone open thoracic surgery. CD34＋ and CD34＋NEGFR＋ cells in the bone marrow and peripheral blood were quantified by flow cytometry. CD34＋/VEGFR＋ cells were defined as EPCs. Mononuclear cells in the bone marrow were isolated by Ficoll density gradient centrifugation and cultured by the EndoCult Liquid Medium KitTM. Colony forming endothelial cells was detected. Immunohistochemistry staining for Dil-ac-LDL and FITC-UEA-1 confirmed the endothelial lineage of these cells. Results CD34＋ and CD34＋NEGFR＋ cells in peripheral blood were （0.07±0.05）% and （0.05±0.02）%, respectively. The number of CD34＋ and CD34＋/VEGFR＋ cells in bone marrow were significantly higher than in blood, （4.41±1.47）% and （0.98±0.65）%, respectively （P 〈0.0001）. Many colony forming units formed in the culture. These cells also expressed high levels of Dil-ac-LDL and FITC-UEA-I. Conclusion This is a novel and feasible approach that can cultivate and purify EPCs from the bone marrow of children with congenital heart disease, and provide seed cells for small calibre vascular tissue engineering.

Epidemiological characteristics of all-cause mortality reviewing out-hospital death under the clouds of COVID-19

TotheEditor:Coronavirus disease2019(COVID-19)has rapidly become a great global infection and broughtabout a wide range of health consequences,including a high number of deaths due to continuous spread.

Perioperative extracorporeal membrane oxygenation in pediatric congenital heart disease:Chinese expert consensus

Background Congenital heart disease(CHD)is one of the main supportive diseases of extracorporeal membrane oxygena-tion in children.The management of extracorporeal membrane oxygenation(ECMO)for pediatric CHD faces more severe challenges due to the complex anatomical structure of the heart,special pathophysiology,perioperative complications and various concomitant malformations.The survival rate of ECMO for CHD was significantly lower than other classifica-tions of diseases according to the Extracorporeal Life Support Organization database.This expert consensus aims to improve the survival rate and reduce the morbidity of this patient population by standardizing the clinical strategy.Methods The editing group of this consensus gathered 11 well-known experts in pediatric cardiac surgery and ECMO field in China to develop clinical recommendations formulated on the basis of existing evidences and expert opinions.Results The primary concern of ECMO management in the perioperative period of CHD are patient selection,cannulation strategy,pump flow/ventilator parameters/vasoactive drug dosage setting,anticoagulation management,residual lesion screening,fluid and wound management and weaning or transition strategy.Prevention and treatment of complications of bleeding,thromboembolism and brain injury are emphatically discussed here.Special conditions of ECMO management related to the cardiovascular anatomy,haemodynamics and the surgical procedures of common complex CHD should be considered.Conclusions The consensus could provide a reference for patient selection,management and risk identification of periop-erative ECMO in children with CHD.

Original article：Extracorporeal membrane oxygenation during double-lung transplantation： single center experience

Background For patients with end-stage lung diseases, lung transplantation is the final therapeutic option. Sequential double-lung transplantation is recognized as an established procedure to avoid cardiopulmonary bypass （CPB）. But some of the sequential double-lung transplantations require CPB support during the surgical procedure for various reasons. However, conventional CPB may increase the risk of bleeding and early allograft dysfunction. Extracorporeal membrane oxygenation （ECMO） is more advantageous than conventional CPB during the perioperative period of transplantation. Replacing traditional CPS with ECMO is promising for those patients needing cardiopulmonary support during a sequential double-lung transplantation procedure. This study aimed to summarize the preliminary experience of ECMO practice in lung transplantation.Methods Between November 2002 and October 2008, twelve patients with end-stage lung diseases undergoing sequential double-lung transplantation were subjected to ECMO during the surgical procedure. Eleven patients were prepared for the procedure via transverse thoracostomy （clamshell） and cannulated through the ascending aorta and right atrium for ECMO. The first patient who underwent bilateral thoracotomy for bilateral sequential lung transplantation required emergency ECMO via the femoral artery and vein during the second lung implantation. The Medtronic centrifugal pump and ECMO package （CBIV97R1, Medtronic, Inc., USA） were used for all of the patients. Results During ECMO, the blood flow rate was set between 1.8-2.0 L.m2.min-1 to keep hemodynamic and oxygen saturation stable; colloid oncotic pressure was maintained at more than 18 mmHg with albumin and hematocrit （HCT） kept at 28% or more. Two patients died early in this series and the other 10 patients were weaned from ECMO successfully. The duration of ECMO was 1.38-67.00 hours, and postoperative intubation was 10,5-67.0 hours. Conclusions As an established technique of cardiopulmonary support, ECMO is helpful to keep hemodynamics stable, while reducing risk factors such as ischemia-reperfusion injury, anticoagulation requirement and systemic inflammatory response for sequential double-lung transplantation compared with conventional CPB.

Myocardial protection during heart surgery in China

Myocardial protection （MP） is the key for cardiopulmonary bypass （CPB） heart surgery. MP during cardiac surgery （CS） aims to preserve myocardial function while providing a bloodless and motionless operating field. Strategies on how to attenuate or prevent post-ischemic myocardial dysfunction that occurs intra-operatively during CS have been discussed for more than half a century. In 1950, Bigelow et al, first reported to decrease myocardial oxygen demand by means of hypothermia. Moreover, Melrose and coworkers2 described the use of electromechanical cardiac arrest induced by potassium infusion, permitting CS to be performed on a non-beating flaccid heart and clear surgical field. The combination of both of these techniques has been the golden standard in MP during surgery until now, allowing surgery with excellent clinical outcome. In 1975, Braimbridge et al introduced a crystalloid solution into clinical practice at St. Thomas Hospital. By the 1980s, blood-based potassium solutions were advocated to further improve MP and to reduce myocardial enzymes release based on the theory that blood would be a superior delivery vehicle for its oxygenating and buffering capacity.Fortunately, the majority of MP strategies now available do allow patients to undergo conventional and complex CS with an operative mortality rate ranging from less than 2% to 4%.

Comparable prognosis in different neonatal histidine-tryptophan-ketoglutarate dosage management

Background:Histidine-tryptophan-ketoglutarate(HTK)is a solution commonly used for organ transplantation.However,there is no certified fixed regimen for on-pump heart surgery in neonates.We aimed to retrospectively evaluate the outcomes related to different HTK dosages and to analyze the safety of high-dosage perfusion.Methods:A total of 146 neonates who underwent on-pump heart surgery with single-shot HTK perfusion were divided into two groups according to HTK dosages:a standard-dose(SD)group(n=63,40 mL/kg<HTK≤60 mL/kg)and a high-dose(HD)group(n=83,HTK>60 mL/kg).Propensity score matching(PSM)was performed to control confounding bias.Results:The SD group had a higher weight(3.7±0.4 vs.3.4±0.4 kg,P<0.0001),a lower proportion of complete transposition of the great artery(69.8%vs.85.5%,P=0.022),a lower cardiopulmonary bypass(CPB)time(123.5[108.0,136.0]vs.132.5[114.8,152.5]min,P=0.034),and a lower aortic x-clamp time(82.9±27.1 vs.95.5±26.0 min,P=0.005).After PSM,44 patients were assigned to each group;baseline characteristics and CPB parameters between the two groups were comparable.There were no significant differences in peri-CPB blood product consumption after PSM(P>0.05).The incidences of post-operative complications were not significantly different between the two groups.There were no significant differences in ventilation time,intensive care unit stay,and post-operative hospital stay(P>0.05).Follow-up echocardiography outcomes at 1 month,3 to 6 months,and 1 year showed that left ventricular ejection fraction and end-diastolic dimension were comparable between the two groups.Conclusions:In neonatal on-pump cardiac surgery patients,single-shot HD(>60 mL/kg)HTK perfusion had a comparable heart protection effect and short-term post-operative prognosis as standard dosage perfusion of 40 to 60 mL/kg.Thus,this study provides supporting evidence of the safety of HD HTK perfusion.

Airway Management in a Child with Goldenhar Syndrome

Goldenhar syndrome, also known as oculo-auriculo-vertebral dysplasia, is characterized by a wide range of congenital anomalies, such as micrognathia, oral cavity malformations, and vertebral anomalies and always causes difficult airway. Awake intubation often cannot be used on children because of inadequate cooperation. In addition, children have higher rates of oxygen consumption, significantly shortening the period of apnea that can be safely tolerated. This study reported a successful orotracheal intubation using the McGrath？ video laryngoscope combined with a fiberoptic bronchoscope （FOB） in a pediatric patient with Goldenhar syndrome.

Veno-arterial extracorporeal membrane oxygenation as a bridge in patients with advanced heart failure:Initial experience in China

To the Editor:Veno-arterial extracorporeal membrane oxygenation(VA-ECMO)has been used as a bridge in patients with advanced heart failure(AdHF)while waiting for heart transplantation(HTx).Many studies reported by developed countries have confirmed the advantages of VA-ECMO in terms of bridge to left ventricular assist device(LVAD)or HTx,with stabilizing the condition and improving the possibility of further treatment of patients.[1-3]Recent data from the Extracorporeal Life Support Organization(ELSO)[4]indicated that ECMO used as a bridge has increased by 20.5%over a decade.However,to date,there are few studies on the bridge experience of VA-ECMO in the mainland of China.