Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study.

BACKGROUND: Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. METHODS: We conducted a multicenter retrospective study to characterize ICI-associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer-Lemeshow test. RESULTS: Forty-four patients were identified, including thirty-five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin-I (cTnI) levels (p < 0.001), higher creatine kinase levels (p = 0.003), higher creatine kinase isoenzyme-MB (CK-MB) levels (p = 0.013), and shorter time to the incidence of adverse cardiovascular events (p = 0.022) after ICI treatment. Twenty-one patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (p = 0.013), higher N-terminal pro-B-type natriuretic peptide levels (p = 0.031), higher creatine kinase levels (p = 0.018), higher CK-MB levels (p = 0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (p = 0.016) compared to non-severe myocarditis patients after ICI treatment. Multivariate logistic regression showed that CK-MB (adjusted odds ratio [OR]: 1.775, 95% confidence interval [CI]: 1.055-2.984, p = 0.031) was the independent risk factor of the development of ICI-associated myocarditis, and cTnI (adjusted OR: 1.021, 95% CI: 1.002-1.039, p = 0.03) and NLR (adjusted OR: 1.890, 95% CI: 1.026-3.483, p = 0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.785 (95% CI: 0.642 to 0.928, p = 0.013) for CK-MB, 0.765 (95% CI: 0.601 to 0.929, p = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, p = 0.016). CONCLUSIONS: Elevated CK-MB after ICI treatment is the independent risk factor for the incidence of ICI-associated myocarditis, and elevated cTnI and NLR after ICI treatment are the independent risk factors for the development of ICI-associated severe myocarditis. CK-MB, cTnI, and NLR demonstrated a promising predictive utility for the identification of ICI-associated myocarditis and severe myocarditis.

Elevated Myoglobin in Patients With Primary Aldosteronism: A Cross-Sectional Study.

Objectives: Primary aldosteronism (PA) is characterized by the autonomous excessive production of aldosterone in the adrenal cortex. Aldosterone is associated with damages to heart muscle and skeletal muscle. The purpose of this study was to evaluate serum levels of muscle injury markers and their associated factors in patients with primary aldosteronism. Methods: We retrospectively enrolled subjects with PA and essential hypertension (EH) who had completed testing for serum high sensitivity troponin T (hs-TnT), creatine kinase isoenzyme MB (CK-MB) and myoglobin from the database of the Chongqing Primary Aldosteronism Study (CONPASS). Univariate and multivariate linear regression analyses were performed to analyze the influencing factors of myocardial injury markers. Results: In total, 278 patients with PA and 445 patients with EH were enrolled in this study. Compared with EH patients, serum concentrations of hs-TnT [7.0 (4.0-12.0) vs. 6.0 (3.0-11.0) ng/L; p=0.005] and myoglobin [24.2 (21.0-38.1) vs. 21.8 (21.0-31.9) µg/L; p=0.023] were significantly higher among PA patients, while no significant difference of CK-MB was found between two groups [1.4 (1.0-2.0) vs. 1.3 (0.9-1.9) µg/L; p=0.154]. Univariate linear regression analysis showed that myoglobin was negatively correlated with serum potassium (ß=-0.31; p<0.01) and positively correlated with plasma aldosterone concentration (ß=0.40; p<0.01) in the PA group, while no significant correlation was found between hs-TnT and biochemical parameters. After adjusting for multiple confounders, myoglobin was negatively correlated with serum potassium (ß=-0.15; p<0.05) and positively correlated with plasma aldosterone concentration (ß=0.34; p<0.01) in the PA group. Conclusions: The serum level of myoglobin was significantly increased in PA patients, and myoglobin was independently correlated with plasma aldosterone concentration.

Protocatechuic aldehyde protects cardiomycoytes against ischemic injury via regulation of nuclear pyruvate kinase M2.

Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction. Protocatechuic aldehyde (PCA) is a major phenolic acid in Chinese herb Danshen (Salvia miltiorrhiza root). This study investigated whether PCA regulated nuclear pyruvate kinase isoform M2 (PKM2) function to protect cardiomyocytes. In rats subjected to isoprenaline, PCA attenuated heart injury and protected cardiomyocytes from apoptosis. Through DARTS and CETSA assays, we identified that PCA bound and promoted PKM2 nuclear translocation in cardiomyocytes exposed to oxygen/glucose deprivation (OGD). In the nucleus, PCA increased the binding of PKM2 to ß-catenin via preserving PKM2 acetylation, and the complex, in cooperation with T-cell factor 4 (TCF4), was required for transcriptional induction of genes encoding anti-apoptotic proteins, contributing to rescuing cardiomyocyte survival. In addition, PCA ameliorated mitochondrial dysfunction and prevented mitochondrial apoptosis dependent on PKM2. Consistently, PCA increased the binding of PKM2 to ß-catenin, improved heart contractive function, normalized heart structure and attenuated oxidative damage in mice subjected to artery ligation, but the protective effects were lost in Pkm2-deficient heart. Together, we showed that PCA regulated nuclear PKM2 function to rescue cardiomyocyte survival via ß-catenin/TCF4 signaling cascade, suggesting the potential of pharmacological intervention of PKM2 shuttle to protect the heart.

A novel scoring system to estimate chemotherapy-induced myocardial toxicity: Risk assessment prior to non-anthracycline chemotherapy regimens.

BACKGROUND: Myocardial toxicity is a common side effect of chemotherapy and is associated with adverse outcomes in cancer patients. Sufficient prediction of chemotherapy-induced myocardiotoxicity (CIMC) is desirable. Therefore, we sought to develop a feasible scoring system to predict CIMC in cancer patients undergoing non-anthracycline chemotherapy. METHODS: We determined a scoring system, the "Cardiotoxicitiy Score" (the CardTox-Score), by multivariable regression of the parameters considered relevant to the development of CIMC, based on previously published data and current guidelines. Variables of the risk model consist of clinical (age, presence of cardiovascular risk conditionsconditions), blood tests (NT-proBNP), and echocardiographic parameters (left ventricular (LV) ejection fraction, LV strain analysis). The CardTox-Score was examined in an internal validation cohort by use of ROC and regression analysis. RESULTS: We prospectively investigated 225 patients (58.21 ± 6.3 years, 52.8% female) who received non-anthracycline myocardiotoxic anticancer agent as a derivation cohort. All patients underwent echocardiography before, during and after anticancer therapy. The mean follow-up duration was 25 ± 4 months. We found the CardTox-Score (>6 points) to be a strong independent predictor (AUC: 0.983, OR: 6.38, 95% CI: 1.6 2.8, p < 0.001) for the development of CIMC with high sensitivity (100%) and specificity (84.2%) in the validation cohort (n = 30, 59.2 ± 6.5 years, 57% female). Moreover, the CardTox-Score appropriately predicted all-cause mortality with high specificity (93.7%) and sensitivity (92.9%) as well (OR: 4.85, AUC: 0.978, p = 0.01). CONCLUSION: The CardTox-Score offers a promising, feasible, and easy-to-handle scoring system for predicting CIMC in cancer patients undergoing non-anthracycline regimes, independent from the type of cancer.

Role of heart fatty acid binding protein in early detection of non ST-elevation myocardial infarct and its comparison with other cardiac markers.

OBJECTIVE: To determine the role of heart fatty acid-binding protein in early detection of non-ST-elevation myocardial infarction and its comparison with two other cardiac markers. METHODS: The cross-sectional study was conducted at Abbasi Shaheed Hospital, Karachi, from June 2012 to June 2014, and comprised patients presenting at the emergency department within two hours of chest pain and who were subsequently referred to the cardiology department with a provisional diagnosis of either unstable angina or non-ST-elevation myocardial infarction. Relevant history was taken on a specific proforma and electrocardiogram as well as routine investigations were done in the emergency department. Blood samples from the subjects were tested for the diagnosis of myocardial infarction through detection of heart fatty acid-binding protein, Troponin-I and Creatine kinase-myocardial band. Sensitivity and specificity of the three markers were calculated keeping coronary angiography as the gold standard. Data was analysed using SPSS 17. RESULTS: Out of 250 patients, 153(61.2%) were males. The overall mean age was 54.45±13.92 years. Sensitivity and specificity of heart fatty acid-binding protein were 80.6% and 78.5% (p<0.05), for Troponin-I, 37.7% and 75% (p>0.05), and for Creatine Kinase-myocardial band, 29.5% and 67.8% (p>0.05). CONCLUSIONS: Heart fatty acid-binding protein was found to be a good diagnostic tool for the detection of non-ST-elevation myocardial infarction.

The value of growth differentiation factor 15 in early diagnosis of acute chest pain / 中华急诊医学杂志

Objective:To explore the value of growth differentiation factor 15 (GDF15) in the early diagnosis of acute chest pain.Methods:A total of 96 patients with acute chest pain admitted to the Emergency Department of Hainan Hospital of PLA General Hospital from January to November 2020 were retrospectively collected. The sex, age, troponin T, creatine kinase, creatine kinase isoenzyme, GDF15 and B-type natriuretic peptide of patients within 30 min after admission were recorded, and the differences of each index in different groups were compared. ROC curve was drawn to evaluate the diagnostic value of GDF15 and TNT/BNP in acute coronary syndrome (ACS). The Gensini score, left ventricular ejection fraction, length of stay in hospital and the number of stents were calculated, and the correlation between these indexes and GDF15 concentration was evaluated.Results:The general trend of acute chest pain was more male than female (72.92% vs. 27.08%) , the oldest group was the UA group (64.67 ± 13.87) years old , the youngest group was cardiac arrest group (47.29 ± 9.99) years old . There were higher rates of hypertension in the STEMI group, NSTEMI group and UA group, and none of the groups showed significant advantage in diabetes. The GDF15 concentration was higher in ACS related chest pain group [(2.360 ± 1.710) ng/mL vs. (1.380 ± 1.040) ng/mL, P<0.01]. The area under the Receiver Operating Characteristic Curve (AUC) of GDF15 combined with TNT was up to 0.863. GDF15 concentration was negatively correlated with ejection fraction, positively correlated with Gensini score, positively correlated with the number of stents implanted, and positively correlated with the length of hospital stay. Conclusions:GDF15 is valuable in the diagnosis and prognosis of acute chest pain. The combination of GDF15 and TNT can improve the diagnostic rate of ACS.

Protocatechuic aldehyde protects cardiomycoytes against ischemic injury

Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction. Protocatechuic aldehyde (PCA) is a major phenolic acid in Chinese herb Danshen (

The predictive value of extra pulmonary multiple factors including creatine kinase-isoenzyme MB in prognosis of patients with acute paraquat poisoning / 中华急诊医学杂志

Objective To investigate the predictive value of extra pulmonary multiple factors including creatine kinase-isoenzyme MB (CK-MB) for the prognosis of patients with acute paraquat poisoning.Methods A retrospectively analysis were conducted on 641 patients who were treated at the First Affiliated Hospital of Zhengzhou University due to oral paraquat poisoning from October 2002 to April 2017.The observation end point was that the patients died from paraquat poisoning within 3 months after admission or were still alive within 3 months after paraquat poisoning.The patients' data were retrieved,including general information,the dose of poison,urinary paraquat concentration,arterial blood gas analysis,alanine transaminase (ALT),total bilirubin (TBIL),uric acid (UA),aspartate transaminase (AST),creatine kinase (CK),CK-MB,B type natriuretic peptide (BNP),lactic dehydrogenase (LDH),high sensitivity troponin T (hsTnT),C-reaction protein (CRP) and procaicitonin (PCT).According to the patient's prognosis within 3 months,the patients were divided into a survival group and a non-survival group.The above indicators were compared between the two groups and the diagnostic value of CK-MB for acute paraquat poisoning was analyzed according to the receiver operating characteristics (ROC) curve.Collect the last arterial blood gas analysis,and laboratory test results were analyzed by binary logistic regression analysis to determine the risk factors for death in patients with acute paraquat poisoning.Results Among the 641 patients with acute paraquat poisoning,315 (49.1％) patients survived and 326 (50.9％) died.Compared with the survival group,patients in the non-survival groupthere were older,had a shorter hospital stay,and had a higher oral paraquat dose and urinary paraquat concentration;Lac,TBIL,UA,AST,CK,CK-MB,BNP,LDH,CRP and PCT were higher,while blood gas analysis index were lower in the non-survival group (P＜0.05).Binary logistic regression analysis showed that the dose of paraquat,CK-MB and AST were closely related to the prognosis of patients with acute paraquat poisoning.The optimal cut-off value of ingestion dose,the first urinary paraquat concentration on admission and CK-MB in predicting the prognosis of patients with acute paraquat poisoning were 7 g (AUC=0.918,sensitivity 80.6％,specificity 87.5％,Yoden index 0.681,P＜0.01),5.16 μg/mL (AUC=0.879,sensitivity 93.8％,specificity 70.1％,Yoden index 0.639,P＜0.01),and 18.2 U/L (AUC=0.846,sensitivity 83.9％,specificity 71.9％,Yoden index 0.558,P＜0.01),respectively.Binary logistic regression analysis of the last biochemical indicators of paraquat poisoning showed that the dose of poison,the last CK-MB,the last SCr,urinary paraquat concentration,and the last blood Na+ were closely related to the prognosis of patients with acute paraquat poisoning.Among them,the last CK-MB＞18.05 U/L often indicated poor prognosis (AUC=0.808,sensitivity 79.7％,specificity 65.8％,Yoden index 0.455,P＜0.01).Conclusions In the treatment of patients with acute paraquat poisoning,there are significant differences in extra pulmonary factors such as heart,liver,kidney,electrolytes and inflammatory markers in patients with different prognosis,so the monitoring and follow-up should be improved,in addition to focusing on the presence and treatment of pulmonary fibrosis.In particular,CK-MB is an independent risk factor for the prognosis of acute paraquat poisoning.In the late stage of poisoning,CK-MB,SCr,and blood Na+ have a strong predictive value for the prognosis of the patients,and we should pay attention to the regular follow-up of the above mentioned laboratory items.

A statistical approach to evaluate the performance of cardiac biomarkers in predicting death due to acute myocardial infarction: time-dependent ROC curve

Background/aim: Myoglobin, cardiac troponin T, B-type natriuretic peptide (BNP), and creatine kinase isoenzyme MB (CK-MB) are frequently used biomarkers for evaluating risk of patients admitted to an emergency department with chest pain. Recently, time- dependent receiver operating characteristic (ROC) analysis has been used to evaluate the predictive power of biomarkers where disease status can change over time. We aimed to determine the best set of biomarkers that estimate cardiac death during follow-up time. We also obtained optimal cut-off values of these biomarkers, which differentiates between patients with and without risk of death. A web tool was developed to estimate time intervals in risk. Materials and methods: A total of 410 patients admitted to the emergency department with chest pain and shortness of breath were included. Cox regression analysis was used to determine an optimal set of biomarkers that can be used for estimating cardiac death and to combine the significant biomarkers. Time-dependent ROC analysis was performed for evaluating performances of significant biomarkers and a combined biomarker during 240 h. The bootstrap method was used to compare statistical significance and the Youden index was used to determine optimal cut-off values. Results : Myoglobin and BNP were significant by multivariate Cox regression analysis. Areas under the time-dependent ROC curves of myoglobin and BNP were about 0.80 during 240 h, and that of the combined biomarker (myoglobin + BNP) increased to 0.90 during the first 180 h. Conclusion: Although myoglobin is not clinically specific to a cardiac event, in our study both myoglobin and BNP were found to be statistically significant for estimating cardiac death. Using this combined biomarker may increase the power of prediction. Our web tool can be useful for evaluating the risk status of new patients and helping clinicians in making decisions.

[Development and application of CK-MB specific monoclonal antibodies].

The aim of this study is to develop creatine kinase isoenzyme MB (CK-MB) specific monoclonal antibodies (mAb), and characterize the monoclonal antibody and further development of quantitative detection assay for CK-MB. The BALB/c mice were immunized with purchased CK-MB antigen, then monoclonal antibodies were prepared according to conventional hybridoma technique and screened by indirect and capture ELISA method. To identify the epitopes and evaluate the classification, purchased creatine kinase isoenzyme MB (CK-MM/BB/MB) antigen was used to identify the epitopes, with immunoblotting and synthetic CK-MM and CK-BB in different linear epitope. A double antibody sandwich ELISA was applied to screen the mAb pairs for CK-MB detection, and the quantitative detection assay for CK-MB was developed. We used 74 cases of clinical specimens for comparison of our assay with Roche's CK-MB assay. We successfully developed 22 strains of hybridoms against CK-MB, these mAbs can be divided into linear, partial conformational CK-MB, CK-MM or CK-BB cross monoclonal antibody and CK-MB specific reaction with partial conformational monoclonal antibody, and CK-MB quantitative detection assay was developed by using partial conformational monoclonal antibody. The correlation coefficient factor r of our reagent and Roche's was 0.930 9. This study established a screening method for CK-MB partial conformational specific monoclonal antibody, and these monoclonal antibodies were analyzed and an established quantitative detection assay was developed. The new assay had a high concordance with Roche's.

Development and application of CK-MB specific monoclonal antibodies / 生物工程学报

The aim of this study is to develop creatine kinase isoenzyme MB (CK-MB) specific monoclonal antibodies (mAb), and characterize the monoclonal antibody and further development of quantitative detection assay for CK-MB. The BALB/c mice were immunized with purchased CK-MB antigen, then monoclonal antibodies were prepared according to conventional hybridoma technique and screened by indirect and capture ELISA method. To identify the epitopes and evaluate the classification, purchased creatine kinase isoenzyme MB (CK-MM/BB/MB) antigen was used to identify the epitopes, with immunoblotting and synthetic CK-MM and CK-BB in different linear epitope. A double antibody sandwich ELISA was applied to screen the mAb pairs for CK-MB detection, and the quantitative detection assay for CK-MB was developed. We used 74 cases of clinical specimens for comparison of our assay with Roche's CK-MB assay. We successfully developed 22 strains of hybridoms against CK-MB, these mAbs can be divided into linear, partial conformational CK-MB, CK-MM or CK-BB cross monoclonal antibody and CK-MB specific reaction with partial conformational monoclonal antibody, and CK-MB quantitative detection assay was developed by using partial conformational monoclonal antibody. The correlation coefficient factor r of our reagent and Roche's was 0.930 9. This study established a screening method for CK-MB partial conformational specific monoclonal antibody, and these monoclonal antibodies were analyzed and an established quantitative detection assay was developed. The new assay had a high concordance with Roche's.

Clinical value in early diagnosis of myocardial damage with h-FABP, cTnI, Mb and CK-Mb joint detection to HFMD in children / 中国医学装备

Objective:To explore the early diagnostic value of joint detection heart type fatty acid binding protein (h-FABP), troponin (cTnI), myoglobin (Mb) and creatine kinase isoenzyme Mb (CK-Mb) in children's hand, foot and mouth disease (HFMD) combined myocardial injury.Methods: Choice 276 cases of HFMD as observation group, and 40 healthy children as control group. Were determined h-FABP, cTnI, Mb and CK-Mb content in serum at different time, analysis of various index level differences and dynamic change between groups in different period.Results: Among 276 patients with HFMD, 57 cases of diagnosed myocarditis, concurrent rate was 20.65%. Within 0~3 hrs, abnormal rate of h-FABP, cTnI, Mb and CK-Mb in serum were 20.29%,1.81%,14.86% and 2.90%, in 276 cases of children with HFMD. The abnormal rate of h-FABP and Mb was obviously higher than that of cTnI and CK-Mb, the results between the difference was statistically significant (x2=35.132,x2=37.063,P<0.01),h-FABP abnormal rate is higher than CK-Mb, the difference was statistically significant(x2=3.175,P<0.05). the,serum h-FABP cTnI, Mb and CK-Mb concentrations in children of HFDM combined with suspicious viral myocarditis were significantly higher than that of control group, the difference had statistical significance (t=37.625,t=23.172,t=17.261,t=18.724,P<0.01). H-FABP and Mb concentration on HFMD combined myocarditis began to rise after the occurrence of 0~3 h, 4~9 h to peak, CTnI and CK-MB 4~9 h to rise, 10~12 h to peak, has been in a higher level in the 12~72 h.Conclusion: HFMD combined myocarditis had a higher incidence, h-FABP is the most sensitive indicator of early diagnosis, followed by Mb. CTnI and CK-MB are parameters of diagnosis sensitivity for HFMD combined with myocarditis in middle-late period.

Parenteral clinical manifestations of 68 cases caused by rotaviral enteritis / 中国基层医药

Objective To analyze rotaviral enteritis outbreak situation parenteral clinical manifestations and understanding of characteristics of multiple organ damage caused by rotaviral enteritis .Methods The clinical data of 68 cases diagnosed as the infection of rotaviral enteritis were retrospectively analyzed .The proportion of observed ap-pearance of multi-organ damage and fever ,acidosis were used as grouping criteria to analyze the relationship with CK-MB abnormalities.Results In 68 cases,including 46 cases of the elevation of CKMB ,9 cases of ECG T wave abnor-malities,symptoms of respiratory tract infection occurred in 37 patients,10 cases of liver function damage symptoms and increase of ALT,37 cases of acidosis,6 cases with symptoms of kidney damage ,skin rashes in 3 cases,2 cases of non febrile convulsions;fever,acidosis and CKMB anomaly had obvious correlation (χ2 =4.390,4.271,all P <0.05 ) .Conclusion Rotaviral enteritis with apparent clinical injury of multiple organ is relatively common .The regu-lar treatments after symptoms are very effective and the prognosis is good .The activity of creatine kinase isoenzyme al-ways is abnormal when the patients have fever ,acidosis ,which suggests that the active control of temperature and cor-rection of acidosis may reduce myocardial injury .

Diagnostic Study on Myocardial Injury in Neonates with Hypoxic Ischemic Encephalopathy by Combined Determination of Cardiac Troponin I,Myoglobin and Creatine Kinase Isoenzyme MB Mass / 医学研究杂志

Objective To study the diagnostic value of myocardial damage by combined determination of cardiac troponin I(cTnI),myoglobin(MYO) and creatine kinase isoenzyme MB mass(CK-MB mass) in neonates with hypoxic ischemic encephalopathy(HIE).Methods The concentrations of serum cTnI,MYO and CK-MB mass were measured in 148 patients with HIE(61 mild,52 moderate and 35 severe) and in 60 healthy subjects by microparticle chemiluminescent immunoassay.Results The study revealed that patients with severe and moderate HIE had sighifieant high levels of cTnI,MYO and CK-MB mass as compared with those with mild HIE and controls(analysis of variance ,P0.05).Not only in mild HIE but also in moderate HIE as well as in severe HIE in the first day of life,the abnormal ratio of MYO were the highest.In the third day of life,the seroprevalence of cTnI,MYO and CK-MB mass in mild HIE group were 6.56%,9.84% and 8.20%,respectively;and those of moderate HIE group were 42.31%,44.23% and 42.31%,respectively;and severe HIE group had the highest abnormal ratio of cTnI(77.14%),MYO(74.29%) and CK-MB mass(77.14%).After the third day,the concentration of MYO in three HIE groups kept reduced but the CK-MB mass and cTnI increased to the peak and maintained above one week at higher levels.Conclusion There is a close association between the cardiac dysfunction and cerebral injury in neonates with HIE.The more cerebral injury the patients have,the more severe cardiac dysfunction they would suffer.

Protective effects of quateranary ammonium salt derivative (F2) of haloperidol on ischemia and reperfusion injury in rat hearts / 中国药理学通报

AIM: To study the effects of quateranary ammonium salt derivative (F2) of haloperidol on ischemia and reperfusion injury in rat hearts. METHODS: Ischemia and reperfusion injury in rat hearts was induced by occluding the left anterior descending coronary artery for 30 min and restoring blood reperfusion for 30 min. F2(1, 2, 4 mg·kg-1, respectively) was intravenously injected before heart ischemia. Plasma creatine kinase (CK), creatine kinase isoenzyme MB(CK-MB), lactate dehydrogenase(LDH), α-Hydroxybutyrate dehydrogenase (HBDH), grutamicoxalacetic transaminase(GOT), superoxide dismutase (SOD) activity and malondiadehyde (MDA) contents were measured. The pathologic changes of ischemia and reperfusion myocardium were observed on the transmission electron microscopy. RESULTS: F2 reduced the release of CK, CK-MB LDH, HBDH, GOT from I/R rat hearts, increased the activity of SOD and decreased the MDA contents. In F2(1mg·kg-1) group, the serum CK-MB LDH HBDH concentration was lowered significantly (vs I/R group P<0.01 or P<0.05). In F2(2 and 4 mg·kg-1) groups serum CK CK-MB LDH HBDH GOT concentration and MDA contents were decreased significantly (vs I/R group P<0.01), and SOD increased significantly (vs I/R group P<0.01). The decrease of CK, CK-MB, LDH, HBDH, MDA in F2(4 mg·kg-1) group was more remarkable than that in F2(2 mg·kg-1) group (P<0.01). CK-MB in F2(4 mg·kg-1) group was lowered than that in Verapamil (2 mg·kg-1) group (P<0.05). For morphology, myocytes of I/R heart showed intracellular edema, disarrangement and rapture of myocardial fiber, damaged mitochondria, marginated and concentrated nucleus. F2 modified these changes. CONCLUSION: F2 may play an apparent role against rat heart ischemia/reperfusion injury in dose-dependent manner.

Protective effects of quateranary ammonium salt derivative (F_2) of haloperidol on ischemia and reperfusion injury in rat hearts / 中国药理学通报

AIM To study the effects of quateranary ammonium salt derivative (F 2) of haloperidol on ischemia and reperfusion injury in rat hearts. METHODS Ischemia and reperfusion injury in rat hearts was induced by occluding the left anterior descending coronary artery for 30 min and restoring blood reperfusion for 30 min. F 2 (1, 2, 4 mg?kg -1 , respectively) was intravenously injected before heart ischemia. Plasma creatine kinase (CK), creatine kinase isoenzyme MB(CK MB), lactate dehydrogenase(LDH),? Hydroxybutyrate dehydrogenase (HBDH), grutamic oxalacetic transaminase(GOT), superoxide dismutase (SOD) activity and malondiadehyde (MDA) contents were measured. The pathologic changes of ischemia and reperfusion myocardium were observed on the transmission electron microscopy. RESULTS F 2 reduced the release of CK,CK MB LDH,HBDH,GOT from I/R rat hearts, increased the activity of SOD and decreased the MDA contents. In F 2 (1mg?kg -1 ) group, the serum CK MB LDH HBDH concentration was lowered significantly (vs I/R group P