Integration of Digital Twins and Artificial Intelligence for Classifying Cardiac Ischemia

Despite advances in intelligent medical care,difficulties remain.Due to its complicated governance,designing,planning,improving,and managing the cardiac system remains difficult.Oversight,including intelligent monitoring,feedback systems,and management practises,is unsuccessful.Current platforms cannot deliver lifelong personal health management services.Insufficient accuracy in patient crisis warning programmes.No frequent,direct interaction between healthcare workers and patients is visible.Physical medical systems and intelligent information systems are not integrated.This study introduces the Advanced Cardiac Twin(ACT)model integrated with Artificial Neural Network(ANN)to handle real-time monitoring,decision-making,and crisis prediction.THINGSPEAK is used to create an IoT platform that accepts patient sensor data.Importing these data sets into MATLAB allows display and analysis.A myocardial ischemia research examined Health Condition Tracking’s(HCT’s)potential.In the case study,75%of the training sets(Xt),15%of the verified data,and 10%of the test data were used.Training set feature values(Xt)were given with the data.Training,Validation,and Testing accuracy rates were 99.9%,99.9%,and 99.9%,respectively.General research accuracy was 99.9%.The proposed HCT system and Artificial Neural Network(ANN)model gather historical and real-time data to manage and anticipate cardiac issues.

Allograft Inflammatory Factor-1 in Cardiac Ischemia Re-perfusion Injury: Release of Molecular Markers in an <i>in Vitro</i>Setting

Initial ischemia/reperfusion injury (IRI) may have an impact on recipient immune responses after transplantation. Allograft inflammatory factor-1 (AIF-1) has been implicated in the regulation of inflammation associated with organ rejection. We hypothesized that it is either passively released from injured tissues during organ procurement, or actively secreted by allograft infiltrating cells contributing to allograft dysfunction. We investigated the impact of IRI in an in vitro study of human heart tissue during the process of transplantation. The mRNA expression levels for both isoforms of the AIF-1, I2 and I3 were significantly increased after 30 minutes reperfusion (AIF-1 I2: p 0.01 vs. AIF-1 I3: p 0.005). Expression levels for IL-18 and the TLRs were increased after 30 minutes of reperfusion. Only IL-18 and TLR-2 were statistically significant (IL-18: p 0.0001 vs. TLR-2: p 0.01). The mRNA expression levels for AIF-1 I2 and IL-18 were decreased from the original levels of ischemia after 60 and 90 minutes reperfusion. The TLR-2 and -4 were presented with minimal levels of reduction after 60 minutes. However, mRNA expression levels for all were decreased to the original levels of ischemia after 90 minutes, except for AIF-1 I3, but the difference was not statistically significant. AIF-1 and IL-18 were specifically detected in myocytes and interstitial tissues by immunohistochemistry (IHC) stain after IRI. TLR-4 was non-specific, and TLR2 was minimally expressed. The study discusses the evidence supporting that the AIF-1 may have therapeutic potential for strategies in the control of innate immune responses early on, after transplantation.

An Investigation of Postmortem Urotensin II Receptor Levels in Brain and Kidney Tissues in a Rat Model of Cardiac Ischemia

This study aimed to investigate changes in postmortem urotensin Ⅱ receptor(UTR)levels in brain and kidney tissues in a rat model of cardiac ischemia.The rats were divided into two groups:a control group and a cardiac ischemia-induced group.Cardiac ischemia was created by an intraperitoneal injection of a single lethal dose of isoproterenol(ISO;850 mg/kg).Plasma UT,blood urea nitrogen,and creatinine levels were determined 0 h postmortem.Brain and kidney UTR mRNA expression levels were determined 0,1,3,6,12,24,4&and 72 h postmortem.The histopathological appearance of brain and kidney tissues was also evaluated.Plasma UT and plasma creatinine levels were increased in the cardiac ischemia-induced group as compared with those in the control group(P<0.001).Ischemia resulted in histopathological changes in brain and cerebellum tissue.The morphological evaluation revealed Purkinje cell degeneration(P=0.037)and dark neurons(P=0.004).The UTR expression level decreased after 1 h postmortem in the brain and after 3 h postmortem in the kidneys in the cardiac ischemia-induced group as compared with that in the control group(P<0.001).The observed changes in UTR expression levels may be valuable in clinical practice in the field of forensic medicine.These changes may be used as a marker in postmortem evaluations of sudden death caused by ischemia-induced cardiac shock.

Protective function of tocilizumab in human cardiac myocytes ischemia reperfusion injury

Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg/mL,3.0 mg/mL,5.0 mg/mL) for 24 h.then cells were cultured in ischemia environment for 24 h and reperfusion environment for 1 h.The MTT and flow cytometry were used to detect the proliferation and apoptosis of human cardiac myocytes,respectively.The mRNA and protein expressions of Bcl-2 and Bax were measured by qRT-PCR and western blot,respectively.Results:Compared to the negative group,pretreated by tocilizumab could significantly enhance the proliferation viability and suppress apoptosis of human cardiac myocytes after suffering ischemia reperfusion injury(P<0.05).The expression of Bcl-2 in tocilizumab treated group were higher than NC group(P<0.05).while the Bax expression were lower(P<0.05).Conclusions:Tocilizumab could significantly inhibit apoptosis and keep the proliferation viability of human cardiac myocytes after suffering ischemia reperfusion injury.Tocilizumab may obtain a widely application in the protection of ischemia reperfusion injury.

A protease-activated receptor 1 antagonist protects against global cerebral ischemia/reperfusion injury after asphyxial cardiac arrest in rabbits

Cerebral ischemia/reperfusion injury is partially mediated by thrombin, which causes brain damage through protease-activated receptor 1（PAR1）. However, the role and mechanisms underlying the effects of PAR1 activation require further elucidation. Therefore, the present study investigated the effects of the PAR1 antagonist SCH79797 in a rabbit model of global cerebral ischemia induced by cardiac arrest. SCH79797 was intravenously administered 10 minutes after the model was established. Forty-eight hours later, compared with those administered saline, rabbits receiving SCH79797 showed markedly decreased neuronal damage as assessed by serum neuron specific enolase levels and less neurological dysfunction as determined using cerebral performance category scores. Additionally, in the hippocampus, cell apoptosis, polymorphonuclear cell infiltration, and c-Jun levels were decreased, whereas extracellular signal-regulated kinase phosphorylation levels were increased. All of these changes were inhibited by the intravenous administration of the phosphoinositide 3-kinase/Akt pathway inhibitor LY29004（3 mg/kg） 10 minutes before the SCH79797 intervention. These findings suggest that SCH79797 mitigates brain injury via anti-inflammatory and anti-apoptotic effects, possibly by modulating the extracellular signal-regulated kinase, c-Jun N-terminal kinase/c-Jun and phosphoinositide 3-kinase/Akt pathways.

Magnetic resonance imaging tracing of transplanted bone marrow mesenchymal stem cells in a rat model of cardiac arrest-induced global brain ischemia

BACKGROUND： Numerous studies have shown that magnetic resonance imaging （MRI） can detect survival and migration of super paramagnetic iron oxide-labeled stem cells in models of focal cerebral infarction. OBJECTIVE： To observe distribution of bone marrow mesenchymal stem cells （BMSCs） in a rat model of global brain ischemia following cardiac arrest and resuscitation, and to investigate the feasibility of tracing iron oxide-labeled BMSCs using non-invasive MRI. DESIGN, TIME AND SETTING： The randomized, controlled, molecular imaging study was performed at the Linbaixin Medical Research Center, Second Affiliated Hospital, Sun Yat-sen University, and the Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, China from October 2006 to February 2009. MATERIALS： A total of 40 clean, Sprague Dawley rats, aged 6 weeks and of either gender, were supplied by the Experimental Animal Center, Sun Yat-sen University, China, for isolation of BMSCs. Feridex （iron oxide）, Gyroscan Inetra 1.5T MRI system, and cardiopulmonary resuscitation device were used in this study. METHODS： A total of 30 healthy, male Sprague Dawiey rats, aged 6 months, were used to induce ventricular fibrillation using alternating current. After 8 minutes, the rats underwent 6-minute chest compression and mechanical ventilation, followed by electric defibrillation, to establish rat models of global brain ischemia due to cardiac arrest and resuscitation. A total of 24 successful models were randomly assigned to Feridex-labeled and non-labeled groups （n = 12 for each group）. At 2 hours after resuscitation, 5 ×10^8 Feridex-labeled BMSCs, with protamine sulfate as a carrier, and 5 ×10^6 non-labeled BMSCs were respectively transplanted into both groups of rats through the right carotid artery （cells were harvested in 1 mL phosphate buffered saline）. MAIN OUTCOME MEASURES： Feridex-labeled BMSCs were observed by Prussian blue staining and electron microscopy. Signal intensity, celluar viability, and proliferative capacity of BMSCs were measured using MRI, Trypan blue test, and M-IT assay, respectively. Distribution of transplanted cells was observed in rats utilizing MRI and Prussian blue staining prior to and 1, 3, 7, and 14 days after transplantation. RESULTS： Prussian blue staining displayed many blue granules in the Feridex-labeled BMSCs. High density of iron granules was observed in the cytoplasm under electron microscopy. According to MRI results, and compared with the non-labeled group, the signal intensity was decreased in the Feridex-labeled group （P 〈 0.05）. The decrease was most significant in the 50 pg/mL Feridex-labeled group （P 〈 0.01）. There were no significant differences in celluar viability and proliferation of BMSCs between the Feridex-labeled and non-labeled groups after 1 week （P 〉 0.05）. Low-signal lesions were detected in the rat hippocampus and temporal cortex at 3 days after transplantation. The low-signal lesions were still detectable at 14 days, and positively stained cells were observed in the hippocampus and temporal cortex using Prussian blue staining. There were no significant differences in signal intensity in the non-labeled group. CONCLUSION： BMSC transplantation traversed the blood-brain barrier and distributed into vulnerable zones in a rat model of cardiac arrest-induced global brain ischemia. MRI provided a non-invasive method to in vivo dynamically and spatially trace Feridex-labeled BMSCs after transplantation.

EFFECT OF ELECTROACUPUNCTURE ON MYOCARDIAL ISCHEMIA INDUCED CHANGES OF CARDIAC SYMPATHETIC ACTIVITY AND INVOLVEMENT OF SPINIAL δ-OPIOID, NMDA-AND NON-NMDA RECEPTORS IN THE RABBIT

Aim: To observe the effect of electroacupuncture (EA) on acute myocardial ischemia (AMI) induced changes of cardiac sympathetic discharges and the effects of some related receptors in the spinal cord. Methods: A total of 53 rabbits anesthetized with mixture solution of 25% urethane (420 mg/kg) and 1.5% chloralose (50 mg/kg) were used in this study. AMI was induced by occlusion of the ventricular branch of the left coronary artery. Discharges of the left cardiac sympathetic nerve were recorded by using a bipolar platinum electrode. Bilateral "Ximen"(PC 40) and "Kongzhui"(LU 6) were stimulated electrically by using an EA therapeutic apparatus or an electrical stimulator. DPDPE δ opiate receptor agonist, 20 nmol, 10 μL, n=8), Naltrindole Hydrochloride (δ opiate receptor antagonist, 20 nmol, 10 μL, n=8), DAP5 (NMDA receptor antagonist, 5 nmol, 10 μL, n=9) and CNQX (non NMDA receptor antagonist, 5 nmol, 10 μL, n=8) were respectively injected into the thoracic subarachnoid space of the spinal cord in different groups, followed by observing their effects on changes of sympathetic activity evoked by EA of the abovementioned acupoints. Results: ① After AMI, sympathetic discharges increased (200.56±79.89%) in 10 cases and decreased (-59.34 ±7.06%) in other 9 cases in comparison with their individual basal values. After EA of "Ximen" (PC 4) and "Kongzhui"(LU 6), AMI induced increase and decrease changes of the sympathetic activity were suppressed significantly, but the effect of EA of LU 6 was weaker than that of EA of PC 4. ② Following EA of PC 4 and LU 6, sympathetic discharges increased significantly in 2 and 4 cases, decreased apparently in 7 and 3 cases, and had no striking changes in 1 and 3 cases respectively. The mean reaction threshold of sympathetic activity after EA of PC 4 and LU 6 were 2.1±0.65 mA and 3.28±1.13 mA separately. ③ After pre treatment with DPDPE, the reaction threshold of the cardiac sympathetic activity to EA of PC 4 elevated significantly (35.89±6.12%); while after pre treatment with Naltrindole, this reaction threshold decreased considerably (84.88±26.58%). Following intrathecal injection of DAP5 (n=9) and CNQX (n=9) , the reaction thresholds of the cardiac sympathetic activity to EA of PC 4 increased obviously (142.06±60.27% and 112.54±28.58% separately). It suggests that spinal δ opioid receptor, NMDA and non NMDA receptors are involved in EA induced changes of sympathetic activity. Conclusion: ① EA could regulate AMI induced changes of cardiac sympathetic activity; and ② spinal δ opioid receptors, NMDA and non NMDA receptors participate in the effect of EA on the cardiac sympathetic activity.

EFFECT OF THE EXCITATION OF ADRENOCEPTORS ON THE PACEMAKER CURRENT I_f OF SHEEP CARDIAC PURKINJE FIBRES IN “ISCHEMIA”SOLUTION

The effect of ischemia like solution and high concentration of isoprenaline and Phenylephrine in that solution on normal pacemaker current If of sheep cardiac Puekinje fibres were observed After perfusing the preparations with “ischemia” solution 15, 30, and 60 min, the amplitude of If current at all measured membrane potentials (from -60 to -120 mV) decreased (n=7,p<0.05)and the activation curve of If current shiftea to left side,E0.5 changed from control value -85.0±3.7 mV to -91.7±4.1 mV at 30 min. Isoprenaline 1×10-6mol/L could increase the amplitude of If current in “ischemia” solution (n= 10, P<0.05) and shift the activation curve of If current back to right side, but it could not completely reverse the inhibitory effect of“ ischemia“. In the presence of propranolol 5 ×10-7 mol/L, 5×10-5 mol/L phenylephrine decreased the amplitude of If current further in “ischemia” solution (n= 7, P<0.05-0.01), the activatior curve of If current shifted to left side further. The above results indicate that the normal pacemaker current was inhibited in “ischemia” condition even in the presence of high concentration of beta and alpha adrenoceptor agonists so the genesis of ischemic ventricular arrhythmia is hardly due to the abnormal enhancement of normal ventricular pacemaker activity.

Adeno-associated Viral Vector Mediated and Cardiac-specific Delivery of CD151 Gene in Ischemic Rat Hearts

Our previous studies demonstrated that CD151 gene promoted neovascularization in ischemic heart model.To improve the delivery efficacy and target specificity of CD151 gene to ischemic heart,we generated an adeno-associated virus（AAV） vector in which CD151 expression was controlled by the myosin light chain（MLC-2v） promoter to achieve the cardiac-specific expression of CD151 gene in ischemic myocardium and to limit unwanted CD151 expression in extracardiac organs.The function of this vector was examined in rat ischemic myocardium model.The protein expression of CD151 in the ischemic myocardium areas,liver and kidney was confirmed by using Western blot,while the microvessels within ischemic myocardium areas were detected by using immunohistochemistry.The results showed that MLC-2v significantly enhanced the expression of CD151 in ischemic myocardium,but attenuated its expression in other organs.The forced CD151 expression could increase the number of microvessels in the ischemic myocardium.This study demonstrates the AAV-mediated and MLC-2v regulated CD151 gene is highly expressed in the ischemic myocardium and cardiac-specific delivery that is more efficiently targets CD151 to the ischemia myocardium after myocardial infarction.

Tauroursodeoxycholic acid and 4-phenyl butyric acid alleviate endoplasmic reticulum stress and improve prognosis of donation after cardiac death liver transplantation in rats

BACKGROUND： Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum （ER） stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death （DCD） liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid （TUDCA） and 4-phenyl butyric acid （PBA）, on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS： Male Sprague-Dawley rats （8-10 weeks） were randomly divided into control group： liver grafts without warm ischemia were implanted; DCD group： warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups： based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS： Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation （P〈0.01, 0.01 and 0.05, respectively） and oxidative indices （P〈0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine）, more severe liver damage （P〈0.01） and up-regulated ER stress signal expressions （P〈0.01 for GRP78, phos-eIF2al, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12）. All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels （P〈0.05）, increased superoxide dismutase activities （P〈0.01）, alleviated liver damage （P〈0.01）, down-regulated ER stress signal expressions （P〈0.01） and improved postoperative survivals （P〈0.01）. CONCLUSIONS： ER stress was involved with DCD liver trans- plantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.

EFFECT OF ELECTROACUPUNCTURE OF THE HEART MERIDIAN ACUPOINTS ON ISCHEMIC CARDIAC FUNCTION IN THE RABBIT

Subjective: To observe the effect of electroacupuncture (EA) of acupoints of the Heart Meridian and Lung Meridian on ischemic cardiac systolic ability for analyzing the relative specific relationship between the Heart Meridian and the heart. Methods: Acute myocardial ischemia (AMI) was produced by intravenous infusion of pituitrin (40 u + 5% glucose injection 500 ml, 60 drips/min) in the rabbit. Left intraventricular pressure (LVP), maximal rising velocity of LVP (dp/dt max), isovolumetric pressure (IP) and end-diastolic pressure (EDP) of the left cardiac ventricle were used as the indexes. Three points of Heart Meridian [HM, from 'Shenmen' (HT 7) to 'Lingdao' (HT 4)] and the three points of Lung Meridian [LM, from 'Taiyuan' (LU 9) to 'Lieque' (LU 7)] were punctured with filiform needles and stimulated with hand-manipulation and electrically with ZY2-1 EA Therapeutic Apparatus. 30 rabbits anesthetized with urethane (1 g/kg) were randomly and evenly divided into control group, HM group and LM group. Result-s: The effects of EA of HM points were evidently superior to those of EA of LM points in promoting the recovery of both AMI-induced decrease of LVP and dp/dtmax, and AMI-induced increase of IP and EDP. Conclusion: Acupoints of Heart Meridian has a relatively specific connection with the heart in comparison with those of Lung Meridian; and the Heart Meridian is a functional whole.

Experimental Hyperthermia during Cardiac Arrest and CPR Is Associated with Severe Spontaneous Hypothermia in Mice

Background: Since genetically engineered mice are becoming more and more available, these animals become of high interest to study physiologic and pathophysiologic pathways of brain ischemia. The aim of this study was to examine body temperature (Tb), physical activity variation and neurohistopathology in mice exposed to normothermic and hyperthermic cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Methods: Male C57Bl/6 mice weighing 22 - 27 g were implanted intraperitoneally with a radio telemeter and subjected to 10 min cardiac arrest followed by cardiopulmonary resuscitation. Normothermia (37.5°C) or hyperthermia (39.0°C) was induced by controlling pericranial temperature during the arrest period. Results: Hyperthermia during the arrest resulted in a Tb decrease during early recovery to a nadir of 28°C ± 0.8°C (mean ± SE) and partially recovered to 34.4°C ± 1°C 36 hrs after CA/CPR. With normothermia during the arrest, Tb depression was less pronounced (nadir of 32.3°C ± 0.3°C) and recovered to physiologic levels within 24 hrs. Coupling of physical activity and body temperature was absent in all animals after CA/CPR. Neuronal injury in the caudoputamen was greater in the hyperthermia group. Conclusions: This study demonstrates that CA/CPR eliminates normal connectivity between body temperature and physical activity and induces long-lasting hypothermia, the depth of which is related to severity of brain injury. Long term temperature monitoring is required in survival murine experiments, if body temperature is a study variable.

Myocardial Protection during Cardiac Surgery: Warm Blood versus Crystalloid Cardioplegia

Purpose: Prevention of myocardial injury is essential during cardiac surgery. Both crystalloid and blood cardioplegia are popular methods for myocardial protection. Most experimental studies have been in favor of blood cardioplegia. The objective of this study is to determine whether the use of warm blood cardioplegia (BCP) is superior to crystalloid cardioplegia (CCP) by means of myocardial injury markers and clinical outcome parameters. Materials and Methods: In a consecutive series of 293 patients, the first 150 received crystalloid cardioplegia, whereas the next 143 patients received blood cardioplegia. Postoperative myocardial injury was assessed by CTnI and CK-MB. Perioperative morbidity and mortality and clinical outcome parameters (need for inotropic support, ICU and hospital stay) were recorded. An unpaired student t-test was performed to analyse continuous postoperative variables relating to myocardial damage. The presence of possible confounders influencing the CTnI or CK-MB concentrations was tested using a student t-test for continuous variables, for categorical variables ANOVA was used. A final longitudinal model was created for CTnI and CK-MB. CTnI was analyzed by a mixed model with random intercept and slope. For all tests performed, statistical significance was 5%. Results: Both groups were well matched with respect to preoperative variables. No significant difference could be found in maximum postoperative levels of CTnI (8.8 ± 18.4 μg/l in BCP vs 9.6 ± 16.5 μg/l in CCP, p = 0.6455) or CK-MB (19.2 ± 31.0 μg/l in BCP vs 26.4 ± 41.5 μg/l in CCP, p = 0.1209). Nor was there any significant difference in other postoperative variables. Testing treatment effect over time proved only significant influence of the surgical intervention type on CTnI levels in time (p < 0.001). Conclusion: This study could not show significantly higher myocardial injury in the group of patients receiving crystalloid cardioplegia versus warm blood cardioplegia. This suggests that warm blood cardioplegia does not confer superior myocardial protection. Surgical intervention type has an important effect on CTnI concentration in time, while the type of cardioplegia does not.

肌醇需求酶1信号通路在自噬改善大鼠冠心病心肌缺血损伤中的作用

目的:基于探讨肌醇需求酶1(IRE1)信号通路在自噬改善大鼠冠心病心肌缺血损伤中的作用。方法:将H9c2细胞分为对照组、IRE1组、缺氧缺糖(OGD)/复氧(OGD/R)组、OGD/R+IRE1组、氯喹组、IRE1+氯喹组、OGD/R+氯喹组、OGD/R+IRE1+氯喹组、OGD组、OGD+氯喹组、OGD/R+IRE1+敲低X盒结合蛋白1(si-XBP1)组、OGD/R+IRE1+过表达X盒结合蛋白1(XBP1-OE)组。通过自噬双标腺病毒(Adv-RFP-GFP-LC3)评估各组细胞的自噬通量。通过免疫荧光和免疫印迹分析X盒结合蛋白1(XBP1)的核转位。另将32只成年雄性C57BL/6 J小鼠随机分为假手术组、缺血/再灌注(I/R)组、IRE1组和I/R+IRE1组,每组8只。通过超声心动图评估大鼠心功能。通过定量免疫印迹分析自噬相关蛋白。结果:(1)细胞试验:与OGD/R组比,OGD/R+IRE1组H9c2细胞中IRE1蛋白表达水平显著增加(P<0.001),微管相关蛋白轻链3蛋白Ⅱ(LC3Ⅱ)和泛素结合蛋白(p62)蛋白表达均显著降低(P均<0.05)。与OGD/R+氯喹组比,OGD/R+IRE1+氯喹组H9c2细胞中LC3Ⅱ和p62蛋白表达均显著增加(P均<0.05)。与对照组比,OGD/R组H9c2细胞中IRE1细胞核/细胞质荧光强度比显著增加(P<0.001);与OGD/R组比,OGD/R+IRE1组IRE1细胞核/细胞质荧光强度增加(P<0.001)。与OGD/R组比,OGD/R+IRE1组核蛋白中的XBP1水平增加(P<0.05)。与OGD/R+IRE1组比,OGD/R+IRE1+si-XBP1组黄色点状体显著减少(P<0.01),OGD/R+IRE1+XBP1-OE组黄色点状体显著增加(P<0.05)。(2)大鼠体内实验:与假手术组比,I/R组左心室射血分数和短轴缩短率均显著降低(P均<0.05)。与I/R组比,I/R+IRE1组心功能障碍改善(P均<0.05)。与假手术组比,I/R组心肌自噬空泡的数量、IRE1、LC3Ⅱ和p62表达均显著增加(P均<0.05)。与I/R组比,I/R+IRE1组心肌自噬空泡的数量、p62表达均显著降低(P均<0.05),心肌组织中IRE1、LC3Ⅱ的表达均增加(P均<0.05)。结论:IRE1通过促进XBP1的核转位恢复了OGD/R和I/R诱导的自噬通量阻断,自噬通量的恢复有助于保护心功能。

Cardio-Protective Effects of Oral Nicorandil in Patients Undergoing Cardiac Valve Surgery

Background: Reduction of myocardial reperfusion injury during cardiopulmonary bypass is an essential requirement for increasing the success rate, decreasing morbidity and mortality of open-heart surgery. Aim: To study the role of pre-operative oral nicorandil in decreasing reperfusion cardiac injury in patients subjected to cardiac valve surgery. Patients and Methods: The study included 62 patients, who were equally randomized into two groups: nicorandil group and control group. Pre-operative, intra-operative and post- operative data were reported and analyzed. Left Ventricle Ejection Fraction (LVEF) was estimated pre-operatively and postoperatively for both groups. Troponin I, creatine kinase-muscle/brain (CK-MB), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured before surgery by 24 hours then 4, 12 and 48 hours after aortic cross clamp removal. Results: Nicorandil considerably decreased TNF-α and IL-6 after 4 and 12 hours following the removal of aortic clamping. It also reduced troponin-I and CKMB at the same time points. However, there were no important changes in IL-6, TNF-α, troponin-I and CK-MB levels in control group in comparison to nicorandil group in the next 48 hours following the removal of aortic clamping. Conclusions: Pre-operative oral nicorandil expressively decreased myocardial reperfusion damage during open heart valve operations, this evidenced by the decrease in the postoperative use of inotropic drugs, considerable reduction of postoperative elevation of cardiac enzymes and inflammatory cytokines with no reported complications.

重楼皂苷Ⅰ预防给药对心肌缺血再灌注损伤大鼠调节PI3K/AKT信号通路的作用研究

目的 从磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)信号通路探讨重楼皂苷I预防给药对心肌缺血再灌注损伤(MI/IR)大鼠的干预机制。方法 将购买的72只SPF级SD大鼠按照随机数字法分为假手术组、模型组、阿司匹林组、重楼皂苷I低、中和高剂量组,每组12只。分组后即给予相应药物干预2周,2周后构建MI/IR模型。模型构建成功24 h后先采用动物彩色多普勒超声仪检测心脏功能,后处死大鼠收集相关组织采用HE染色观察心肌病理学、TTC法检测心肌梗死面积,试剂盒检测心功能指标[乳酸脱氢酶(LDH)、肌酸激酶同工酶MB(CK-MB)和谷草转氨酶(AST),抗氧化指标丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)],TUNNEL染色检测心肌细胞凋亡特点,Western blot检测心肌PI3K、AKT、B细胞淋巴瘤/因子2(Bcl-2)、Bcl-2相关蛋白(Bax)蛋白表达。结果 假手术组心肌纤维排列整齐、无水肿,模型组有心肌纤维断裂,重楼皂苷I低、中、高剂量组和阿司匹林组明显改善心肌纤维断裂情况。与假手术组相比,模型组大鼠心肌梗死面积、LVEDP、LDH、CK-MB、AST和MDA明显升高(P<0.05),LVDP、+dp/dtmax、-dp/dtmax、SOD和GSH明显降低(P<0.05);相较于模型组,阿司匹林组和重楼皂苷I低、中、高剂量组干预后,心肌梗死面积、LVEDP、LDH、CK-MB、AST和MDA明显降低(P<0.05),LVDP、+dp/dtmax、-dp/dtmax、SOD和GSH则明显升高(P<0.05)。Tunnel染色可见,假手术组几乎没有心肌细胞凋亡,而模型组呈现出明显的大量的细胞凋亡;与模型组相比,阿司匹林组和重楼皂苷I低、中、高剂量组凋亡情况明显好转。此外,与假手术组相比,模型组大鼠心肌PI3K、AKT和Bcl-2蛋白表达均明显降低,Bax明显升高(均P<0.05);相较于模型组,重楼皂苷I低、中、高剂量组以及阿司匹林组PI3K、AKT和Bcl-2蛋白表达均明显升高,Bax蛋白表达明显降低(均P<0.05)。结论 重楼皂苷I对心肌缺血再灌注损伤有一定的预防作用,其作用机理可能与其能够调节PI3K/AKT信号通路有关。

心搏骤停后综合征的治疗方法研究进展

心搏骤停后综合征(PCAS)是心搏骤停的严重并发症,致死、致残率极高。如何采用及时有效的治疗措施提高PCAS患者的救治成功率已成为急诊医学界关注和研究的热点问题之一。目前,PCAS的治疗措施主要包括呼吸支持、循环支持、脑保护、冠状动脉血运重建等。本文对当前PCAS的主要治疗方法进行总述,以期为临床医生救治此类患者和开展进一步的研究提供参考。

心源性头痛1例

心源性头痛是由潜在的冠状动脉病变所致,表现为头痛伴或不伴胸部症状的罕见疾病。头痛症状常常由于牵涉痛、心肌缺血引起的颅内压升高、大量致痛的神经化学介质释放和脑皮质灌注不足引起。鉴于该疾病总体患病率低、缺乏冠心病典型的胸痛表现,且可能与神经系统疾病引发的头痛难以鉴别,常常造成疾病准确诊断和治疗的延误。现报道1例仅表现头痛的急性冠状动脉综合征患者,通过经皮冠状动脉介入治疗完成血运重建,并给予标准的二级预防药物治疗。术后随访至今6个月,活动耐量较前明显提高,未再发作头痛。本病例报道旨在提高对心源性头痛患者的认识,以期早期识别并及时干预,最终改善症状和预后。

心脏体外震波治疗对冠心病患者心肌灌注及心电图的影响

目的探讨心脏体外震波治疗(CSWT)对冠心病患者负荷心肌灌注扫描及心电图结果的影响。方法纳入2016年12月至2022年8月因冠心病在北京医院住院诊治并行CSWT的患者。CSWT为3个月方案,共9次治疗。收集冠心病患者行CSWT前后的临床基本资料、心肌灌注扫描数据和心电图数据。比较CSWT前后心肌灌注扫描结果和心电图参数的变化。结果共有55例冠心病患者,其中男43例,平均年龄为(67.45±8.96)岁。CSWT前后12导联心电图ST段最大位移均无明显变化,心肌灌注扫描显示左心室整体负荷灌注总分(P=0.031)和整体可逆灌注总分(P=0.024)显著改善,静息左心室整体缺血面积显著缩小(P=0.034),差异均有统计学意义。靶节段负荷灌注评分(P=0.002)、靶节段可逆灌注评分(P=0.002)、靶节段负荷缺血面积(P=0.001)明显改善,差异均有统计学意义。结论CSWT对冠心病难治性心绞痛患者心电图ST段最大位移无影响,有助于改善心肌血流灌注,缩小缺血范围。

缺血后处理对心肌缺血再灌注大鼠心功能、心肌细胞凋亡和心肌组织线粒体凋亡相关分子表达的影响

目的分析缺血后处理(ischemic postconditioning,IP)对心肌缺血再灌注(ischemia-reperfusion,IR)大鼠心功能、心肌细胞凋亡和心肌组织线粒体凋亡相关分子表达的影响。方法将40只8周龄雄性SD大鼠分笼喂养,每笼5只,适应性饲养7 d,随机分为空白对照组(对照组)、假手术组(S组)、心肌IR造模组(IR组)、心肌IP造模+IP处理组(IP组),每组各10只。术后4 h使用生物机能实验系统记录大鼠心功能[左心室收缩压(left ventricular systolic pressure,LVSP)、心室舒张末压(left ventricular enddiastolic pressure,LVEDP)、左心室压变化速率最大值(±dp/dtmax)]。采用TUNEL法检测心肌细胞凋亡指数,采用RT-PCR法检测心肌细胞凋亡相关蛋白BCL-2、BAX及天冬氨酸特异性半胱氨酸蛋白酶-3(cysteinylaspartate-specific proteinase 3,Caspase-3)、法尼酯衍生物X受体(farnesyl X receptor,FXR)、小异二聚体配体(small heterodimer partner,SHP)相对表达量。蛋白质印迹法检测心肌细胞线粒体凋亡通路标志物细胞色素C(cytochrome C,Cyt-C)的释放量。结果IP组及IR组LVEDP、心肌细胞凋亡指数、心肌组织BAX、CASPASE-3、FXR、SHP相对表达量及心肌细胞胞浆Cyt-C蛋白灰度值均高于S组、对照组(P<0.05),IR组LVEDP、心肌细胞凋亡指数、BAX、CASPASE-3、FXR、SHP相对表达量及Cyt-C蛋白灰度值高于IP组(P<0.05);IP组及IR组LVSP、±dp/dtmax、心肌组织BCL-2相对表达量均低于S组、对照组(P<0.05),IR组LVSP、±dp/dtmax、心肌组织BCL-2相对表达量均低于IP组(P<0.05)。结论IP处理可减轻大鼠心肌IR损伤,改善心功能,可能与调控BCL-2/BAX、FXR/SHP等凋亡相关信号蛋白的表达有关。