Myocardial Ischemia Group Research Articles

Abstract P130: Predictive value of the MCG-based Nomogram model for the anatomical and functional evaluation of coronary artery lesions

Objective: Optical coherence tomography (OCT) is an intravascular imaging technology that can provide cross-sectional images of coronary arteries, which can more accurately assess the condition of coronary artery lesions and the degree of vascular stenosis. It is an important method for the anatomical evaluation of coronary artery lesions. Radionuclide myocardial perfusion imaging (MPI) is a commonly used non-invasive method for functional evaluation of myocardial ischemia in clinical practice. The clinical application of these two methods is greatly limited due to operational risk and high cost. This study aimed to explore the potential predictive value of the MCG-based Nomogram model for the anatomical and functional evaluation of coronary artery lesions. Methods: We reviewed the patients who were hospitalized in the cardiovascular department of our hospital from October 2021 to July 2023 for MCG test. A total of 137 patients were included in the OCT subgroup, including 48 patients in the severe coronary artery stenosis group (inclusion criteria: OCT showed coronary artery area stenosis ≥70.0%) and 89 patients in the control group (inclusion criteria: OCT showed coronary artery area stenosis <50.0% or CCTA showed no coronary artery stenosis). A total of 46 patients were included in the MPI subgroup, including 10 patients in the severe myocardial ischemia group (inclusion criteria: MPI showed abnormal perfusion scores of at least one ventricular segment ≥3 points) and 36 patients in the control group (inclusion criteria: MPI showed abnormal perfusion scores of all ventricular segments ≤2 points). The Nomogram model was used to predict the results of patients in the two subgroups, and the results were compared with the OCT and MPI results. The sensitivity, specificity and Youden index were calculated. Results: The Nomogram model based on MCG had a sensitivity of 70.8%, a specificity of 85.4%, and a Youden index of 0.562 for predicting OCT results. The sensitivity, specificity and Youden index of Nomogram model for predicting MPI results were 70.0%, 72.2% and 0.422, respectively. Conclusions: The MCG-based Nomogram model has good prediction accuracy for the anatomical and functional evaluation of coronary artery lesions, which has potential application value.

The clinical value of noninvasive left ventricular myocardial work in the diagnosis of myocardial ischemia in coronary heart disease: a comparative study with coronary flow reserve fraction.

The prompt and precise identification of hemodynamically significant coronary artery lesions remains an ongoing challenge. This study investigated the diagnostic value of non-invasive global left ventricular myocardial work indices by echocardiography in functional status of coronary artery disease (CAD) patients with myocardial ischemia using fractional flow reserve (FFR) as the gold standard. A total of 77 consecutive patients with clinically suspected CAD were prospectively enrolled. All participants sequentially underwent echocardiography, invasive coronary angiography (ICA) and FFR measurement. According to the results of ICA, patients were divided into myocardial ischemia group (FFR ≤ 0.8, n = 27) and non-myocardial ischemia group (FFR > 0.8, n = 50). Myocardial work indices including global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), global positive work (GPW), global negative work (GNW), global systolic constructive work (GSCW) and global systolic wasted work (GSWW) were obtained by using the non-invasive left ventricular pressure strain loop (PSL) technique. Compared with the non-myocardial ischemia group, GWI, GCW, GPW and GSCW were significantly decreased in the myocardial ischemia group at either the 18-segment level or the 12-segment level (P < 0.001). At the 18-segment level, GWI < 1783.6 mmHg%, GCW < 1945.4 mmHg%, GPW < 1788.7 mmHg% and GSCW < 1916.5 mmHg% were optimal cut-off value to detect myocardial ischemia with an FFR ≤ 0.8. Global left ventricular myocardial work indices by echocardiography exhibited a good diagnostic value in patients with CAD and may have a good clinical significance for the screening of suspected myocardial ischemia.

Positive effects of low-dose S-ketamine on preventing myocardial injury after thoracoscopic lobectomy in patients aged 70 to 85

ObjectiveTo investigate the effects of low-dose S-ketamine on marker of myocardial injury (BNP, hs-cTnT and HFABP) after thoracoscopic lobectomy in patients aged 70 to 85.MethodsOne hundred patients (four cases excluded) aged 70–85 years, with body mass index 18–24 kg·m−2 and American Society of Anesthesiologists physical status II–III, scheduled for elective lobectomy from April 2022 to April 2023, were selected. The patients were divided into two groups by a random number table method, namely, the low-dose S-ketamine combined with GDFT group (group S) and the control group (group C), with 48 cases in each group. In group S, a low dose of S-ketamine (0.2 mg/kg) was given 1 min before intubation, and the maintenance dose was 0.12 mg·kg−1·h−1. Fluid therapy, guided by cardiac index (CI), changes in stroke volume (△SV), and other dynamic indicators, was used for rehydration during the operation. Group C was given the same amount of normal saline (0.2 mg/kg) 1 min before intubation, and the same rehydration therapy was adopted during the operation. The mean arterial pressure (MAP) and heart rate (HR) of the two groups were observed and recorded immediately after entering the operating room (T0), immediately after intubation (T1), immediately after the beginning of one-lung ventilation (OLV) (T2), immediately after the beginning of surgery (T3), immediately after the end of OLV (T4), and at the end of surgery (T5). The intraoperative fluid intake and output and the use of vasoactive drugs were recorded. The plasma levels of heart-type fatty acid–binding protein (HFABP), high-sensitivity troponin T (hs-cTnT), brain natriuretic peptide (BNP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) were recorded 24 h before operation and 24 and 48 h after operation. Visual analogue scale (VAS) pain scores at rest were recorded at 2 (V1), 6 (V2), 12 (V3), 24 (V4), and 48 h (V5) after operation, and the occurrence of myocardial ischemia during hospitalization was noted.ResultsCompared with group C, MAP was significantly higher at T1–T5 in group S (P < 0.05), and the plasma concentrations of IL-6, IL-8, TNF-α, BNP, hs-cTnT, and HFABP were significantly lower at 24 and 48 h after operation (P < 0.05). The VAS pain scores at 2, 6, 12, 24, and 48 h after operation, the number of effective patient-controlled intravenous analgesia (PCIA) compressions, and the total number of PCIA compressions within 48 h after operation were significantly decreased (P < 0.05). Compared with group C, The hospitalization days, and the incidence of postoperative myocardial ischemia in group S were lower (P < 0.05). There were no significant intergroup differences in urine volume, extubation time, the incidence of postoperative atrial fibrillation, bleeding volume, colloid infusion volume, total fluid infusion volume, and the incidence of rescue analgesia.ConclusionsLow-dose S-ketamine can reduce the levels of hs-cTnT, HFABP, and BNP in older patients after pulmonary lobectomy, which has a positive effect on preventing myocardial injury.Trial registrationThis study was registered on CHICTR (registration No. ChiCTR2300074475). Date of registration: 08/08/2023.

The Correlation between Region-specific Epicardial Adipose Tissue and Myocardial Ischemia Defined by CT-FFR in Type 2 Diabetes Mellitus Patients.

Epicardial Adipose Tissue (EAT) accumulation is closely associated with the presence and severity of coronary artery disease (CAD), myocardial ischemia, plaque vulnerability, and major adverse cardiovascular events. The aim of this study was to investigate the correlation between myocardial ischemia defined by computed tomography-derived fractional flow reserve (CT-FFR) and region-specific EAT in patients with type 2 diabetes mellitus (T2DM). Between January 2022 and May 2023, 200 T2DM patients were randomly selected from the Department of Endocrinology in The Central Hospital of Wuhan. These patients were divided into two groups based on myocardial ischemia defined by CT-FFR: myocardial ischemia group (152 cases) and control group (48 cases). Both groups of patients used a post-treatment workstation to measure the thickness of region-specific EAT. Receiver operating characteristic (ROC) curve analysis and binary logistic regression were used to evaluate the correlation between various parameters and myocardial ischemia. Patients in the myocardial ischemia group had significantly higher values of age, male gender, systolic blood pressure, total cholesterol, triglycerides, LDL, HDL, fasting blood glucose, fasting insulin, HOMA-IR, EAT thickness in right ventricular wall, left atrioventricular groove, and superior and inferior interventricular groove. ROC curve analysis results showed that EAT thickness in the left atrioventricular groove had the largest area under the ROC curve for diagnosing myocardial ischemia (0.837 [95% CI 0.766-0.865]; P < 0.001). Binary logistic regression analysis showed that EAT thickness in the left atrioventricular groove was an independent risk factor for myocardial ischemia in patients with T2DM (P < 0.05). The EAT thickness in the left atrioventricular groove is an independent risk factor for myocardial ischemia in patients with T2DM. Adipose tissue in the left atrioventricular groove region plays a major role in EAT-mediated CAD.

Co-treatment with bone marrow-derived mesenchymal stem cells and curcumin improved angiogenesis in myocardium in a rat model of MI.

The cardioprotective properties of mesenchymal stem cells and the therapeutic potential of curcumin (CUR) have been explored. Combining these approaches may enhance stem cell effectiveness and expedite healing. This study aimed to investigate the synergistic effects of co-treating bone marrow mesenchymal stem cells (BMSCs) with curcumin on vascular endothelial growth factor (VEGF) levels, in a rat model of myocardial ischemia (MI). Sixty-five male rats were divided into four groups: G1 (healthy control), G2 (MI induced by isoproterenol hydrochloride), G3 (treated with BMSCs), and G4 (co-treated with curcumin and BMSCs). Blood and tissue samples were collected at specific time points (day 1, 7, 15 and 21) after MI induction. Serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin I (cTnI), aspartate aminotransferase (AST), CK-MB and VEGF were measured. VEGF mRNA and protein expression were evaluated using RT-qPCR and Western blot techniques. Histopathological assessments were performed using H&E staining and CD31 immunofluorescence staining. VEGF expression significantly increased on days 7 and 15 in the CUR-BMSCs group, peaking on day 7. Western blot analysis confirmed elevated VEGF protein expression on days 7 and 15 post-MI. ELISA results demonstrated increased serum VEGF levels on days 7 and 15, reaching the highest level on day 7 in CUR-BMSCs-treated animals. Treated groups showed lower levels of LDH, AST, CK, CK-MB and cTnI compared to the untreated MI group. H&E staining revealed improved myocardial structure, increased formation of new capillaries, in both treatment groups compared to the MI group. Combining curcumin with BMSCs promotes angiogenesis in the infarcted myocardium after 15days of MI induction. These findings suggest the potential of this combined therapy approach for enhancing cardiac healing and recovery.

Relationship between dynamic electrocardiogram and CRP, IL-6, ET-1 expression in myocardial ischemia patients with coronary heart disease.

This study aimed to observe the relationship between dynamic electrocardiogram and CRP, IL-6, and ET-1 expression in individuals with myocardial ischemia and Coronary Heart Disease (CHD). For this purpose, from January 2021 to December 2022, 80 patients with CHD were admitted to the hospital to determine the presence of myocardial ischemia according to coronary angiography. The individuals were separated into a myocardial ischemia group and a no myocardial ischemia group. Dynamic electrocardiogram (DCG), serum CRP, IL-6, and ET-1 were used in the two groups, respectively. The association between dynamic electrocardiogram indexes and serum CRP, IL-6, and ET-1 levels was discovered using a Pearson correlation analysis. Results showed that the SDNN, SDANNI, rMSSD and PNN50 of Patients with Myocardial Ischemia (PWMI) were lower than individuals with CHD without myocardial ischemia (P<0.05). CRP and IL-6 were negatively correlated with SDNN, SDANNI, rMSSD and PNN50 (P<0.001). ET-1 had a bad relationship with rMSSD and PNN50 (P<0.001). Correlation heat map analysis showed that the color difference of IL-6 was the most obvious between PWMI and Patients Without Myocardial Ischemia (POMI), and IL-6 was more strongly correlated with dynamic electrocardiogram-related indexes of myocardial ischemia. In individuals with CHD myocardial ischemia, there is a negative connection between the DCG index and the production of the inflammatory cytokines CRP, IL-6, and ET-1. In conclusion, CRP, IL-6, and ET-1 levels should be monitored in patients with decreased heart rate variability, so as to further determine the level of micro-inflammation and endothelial function.

Incremental value of epicardial fat volume on predicting obstructive coronary artery disease with myocardial ischemia

Objective: This study aimed to investigate the association between epicardial fat volume (EFV) and obstructive coronary artery disease (CAD) with myocardial ischemia, and evaluate the incremental value of EFV on top of traditional risk factors and coronary artery calcium (CAC) in predicting obstructive CAD with myocardial ischemia. Methods: This study was a retrospective cross-sectional study. Patients with suspected CAD who underwent coronary angiography (CAG) and single photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) at the Third Affiliated Hospital of Soochow University from March 2018 to November 2019 were consecutively enrolled. EFV and CAC were measured by non-contrast chest computed tomography (CT) scan. Obstructive CAD was defined as coronary artery stenosis≥50% in at least one of the major epicardial coronary arteries, and myocardial ischemia was defined as reversible perfusion defects in stress and rest MPI. Obstructive CAD with myocardial ischemia was defined in patients with coronary stenosis severity≥50% and reversible perfusion defects in the corresponding areas of SPECT-MPI. Patients with myocardial ischemia bot without obstructive CAD were defined as none-obstructive CAD with myocardial ischemia group. We collected and compared the general clinical data, CAC and EFV between the two groups. Multivariable logistic regression analysis was performed to identify the relationship between EFV and obstructive CAD with myocardial ischemia. ROC curves were performed to determine whether addition of EFV improved predictive value beyond traditional risk factors and CAC for obstructive CAD with myocardial ischemia. Results: Among the 164 patients with suspected CAD, 111 patients were males, and average age was (61.4±9.9) years old. 62 (37.8%) patients were included into the obstructive CAD with myocardial ischemia group. 102 (62.2%) patients were included into the none-obstructive CAD with myocardial ischemia group. EFV was significantly higher in obstructive CAD with myocardial ischemia group than in none-obstructive CAD with myocardial ischemia group ((135.63±33.29)cm3 and (105.18±31.16)cm3, P<0.01). Univariate regression analysis showed the risk of obstructive CAD with myocardial ischemia increased by 1.96 times for each SD increase in EFV(OR 2.96; 95%CI, 1.89-4.62; P<0.01). After adjustment for traditional risk factors and CAC, EFV remained as an independent predictor for obstructive CAD with myocardial ischemia (OR, 4.48, 95%CI, 2.17-9.23; P<0.01). Addition of EFV to CAC and traditional risk factors was related to larger AUC for predicting obstructive CAD with myocardial ischemia (0.90 vs. 0.85, P=0.04, 95%CI: 0.85-0.95) and the global chi-square increased by 21.81 (P<0.05). Conclusions: EFV is an independent predictor for obstructive CAD with myocardial ischemia. Addition of EFV to traditional risk factors and CAC has incremental value for predicting obstructive CAD with myocardial ischemia in this patient cohort.

Prediction of myocardial ischemia in coronary heart disease patients using a CCTA-Based radiomic nomogram.

The present study aimed to predict myocardial ischemia in coronary heart disease (CHD) patients based on the radiologic features of coronary computed tomography angiography (CCTA) combined with clinical factors. The imaging and clinical data of 110 patients who underwent CCTA scan before DSA or FFR examination in Changzhou Second People's Hospital, Nanjing Medical University (90 patients), and The First Affiliated Hospital of Soochow University (20 patients) from March 2018 to January 2022 were retrospectively analyzed. According to the digital subtraction angiography (DSA) and fractional flow reserve (FFR) results, all patients were assigned to myocardial ischemia (n = 58) and normal myocardial blood supply (n = 52) groups. All patients were further categorized into training (n = 64) and internal validation (n = 26) sets at a ratio of 7:3, and the patients from second site were used as external validation. Clinical indicators of patients were collected, the left ventricular myocardium were segmented from CCTA images using CQK software, and the radiomics features were extracted using pyradiomics software. Independent prediction models and combined prediction models were established. The predictive performance of the model was assessed by calibration curve analysis, receiver operating characteristic (ROC) curve and decision curve analysis. The combined model consisted of one important clinical factor and eight selected radiomic features. The area under the ROC curve (AUC) of radiomic model was 0.826 in training set, and 0.744 in the internal validation set. For the combined model, the AUCs were 0.873, 0.810, 0.800 in the training, internal validation, and external validation sets, respectively. The calibration curves demonstrated that the probability of myocardial ischemia predicted by the combined model was in good agreement with the observed values in both training and validation sets. The decision curve was within the threshold range of 0.1-1, and the clinical value of nomogram was higher than that of clinical model. The radiomic characteristics of CCTA combined with clinical factors have a good clinical value in predicting myocardial ischemia in CHD patients.

Discussion on Repolarization Reserve between Patients with Coronary Heart Disease and Normal Controls.

Objective To investigate the repolarization reserve of normal controls (NCs) and patients with coronary heart disease (CHD). Methods From January 1st, 2010 to December 31st, 2018, 200 age- and gender-matched inpatients in the Second Hospital of Shanxi Medical University and Heji Hospital Affiliated to Changzhi Medical College were selected for treadmill exercise test (TET), including 67 patients in the myocardial ischemia group, 66 patients in the suspected myocardial ischemia group, and 67 patients in the normal control group. Coronary angiography (CAG) was performed on 49 of 133 patients in the myocardial ischemia group and the suspected myocardial ischemia group, and 9 positives and 40 negatives were identified. The heart rate (HR) and QT interval of TET examiners before exercise, during exercise (90 beats/min, 120 beats/min, maximum HR), and in the recovery period (1 minute and 3 minutes after exercise) were reviewed, and QTc values were calculated after being corrected by BaZett's. Results The mean QTc values in NCs were all below 452 ms, before exercise, during exercise (90 beats/min, 120 beats/min and maximum HR), and during the recovery period (1 minute and 3 minutes after exercise). The comparison results of the RR interval between the two groups revealed P > 0.05, indicating no statistical significance. Significant differences were present when comparing the QT intervals when the HRs were 90 beats/minute and 120 beats/minute during exercise (P < 0.05). And comparing the QTc values, it was found that the QTc values during different exercise periods were statistically different between groups (P < 0.05). Conclusions NCs have good repolarization reserve. CAG can confirm true myocardial ischemia patients (i.e., patients with CHD) among myocardial ischemia and suspected myocardial ischemia patients screened by TET. Patients with positive CAG have poor repolarization reserve as QT interval represents ventricular repolarization adaptability.

Incremental value of epicardial fat volume to coronary artery calcium score and traditional risk factors for predicting myocardial ischemia in patients with suspected coronary artery disease

BackgroundEpicardial fat volume (EFV) has been reported to be associated with coronary artery disease (CAD). CAD is the leading cause of myocardial ischemia and myocardial ischemia is closely related to major adverse cardiovascular events. We hypothesized that EFV could provide incremental value to traditional risk factors and coronary artery calcium score (CACS) in predicting myocardial ischemia in Chinese patients with suspected CAD. MethodsWe retrospectively studied 204 Chinese patients with suspected CAD who underwent single-photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) combined with computed tomography (CT). Pericardial contours were manually defined, and EFV was automatically calculated. A reversible perfusion defect with summed difference score (SDS) ≥ 2 was defined as myocardial ischemia. ResultsThe myocardial ischemia group had higher EFV than normal MPI group (137.80 ± 34.95cm3 vs. 106.63 ± 29.10 cm3, P < .001). In multivariable logistic regression analysis, high EFV was significantly associated with myocardial ischemia [odds ratio (OR): 8.30, 95% CI: 3.72-18.49, P < .001]. Addition of EFV to CACS and traditional risk factors could predict myocardial ischemia more effectively, with larger AUC .82 (P < .001), positive net reclassification index .14 (P = .04) and integrated discrimination improvement .14 (P < .001). The bootstrap resampling method (times = 500) was used to internally validation and calculate the 95% confidence interval (CI) of the AUC (95% CI .75-.87). The calibration curve for the probability of myocardial ischemia demonstrated good agreement between prediction and observation. ConclusionsIn Chinese patients with suspected CAD, EFV was significantly associated with myocardial ischemia, and improved prediction of myocardial ischemia above traditional risk factors and CACS.

Association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan

BackgroundThere is an ongoing controversy regarding the necessity of single-photon emission computed tomography (SPECT) for patients with ischemic heart diseases after the publication of the results of the ISCHEMIA trial. We aimed to evaluate the association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan. MethodsFrom the data of 2780 patients with stable angina who were enrolled prospectively between January 2006 and March 2008 in Japan and had undergone physician-referred non-invasive imaging tests (Japanese Coronary-Angiography or Myocardial Imaging for Angina Pectoris Study), 1205 patients managed with SPECT were stratified by 10 % myocardial ischemia. Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalization for heart failure, and late revascularization, were followed-up for 1 year. ResultsPatients with ≥10 % myocardial ischemia (n = 173) were less likely to be women than patients with <10 % myocardial ischemia (n = 1032) and had a significantly higher 1-year cumulative incidence of MACEs (6.9 % vs. 1.8 %, p < 0.0001). After adjusting for confounders, the risk of ≥10 % myocardial ischemia relative to <10 % myocardial ischemia for MACEs remained significant [adjusted hazard ratio (95 % confidence interval), 2.40 (1.09–5.26), p = 0.029]. After adjusting including treatments, the risk of MACEs became insignificant between the ≥10 % myocardial ischemia group and the <10 % myocardial ischemia group [adjusted hazard ratio (95 % confidence interval), 1.04 (0.45–2.45), p = 0.92]. ConclusionThe presence of ≥10 % myocardial ischemia at diagnosis was significantly associated with the 1-year risk for MACEs in Japanese patients with suspected coronary artery disease.

The effect of Guizhi decoction on inflammatory response induced by myocardial ischemia

We aim to explore the influence of Guizhi decoction(GD) on inflammatory response in myocardial ischemia models. 45 New Zealand rabbits were divided into three groups randomly: sham control group, myocardial ischemia group and myocardial ischemia + Guizhi decoction treatment group. The rabbits were treated with Guizhi decoction or saline for 20 days. After that, the myocardial ischemia model was created by left anterior descending coronary artery ligation. Color Doppler Echocardiography computed the ejection fraction (EF). Serum content of MyD88 and TNF-α and concentration of cardiac markers (CK-MB, CK, LDH and cTnT) was measured. After ligation, ST segment was elevated. However, 15 rabbits died due to operation and postoperative care, and were excluded from this study. The final sample size was sham control group (n=10), myocardial ischemia group (n=10) and Guizhi decoction group (n=10) Compared with the sham control group, the ejection fraction was decreased and the expression of the TLR4, MyD88, TNF-α,CK-MB, CK, LDH and cTnT in myocardial ischemia group was increased (p<0.05). After treatment with Guizhi decoction, EF was improved and related inflammatory response factors were decreased (p <0.05). Pretreatment with Guizhi decoction attenuated the level of proinflammatory markers and improved heart function in animal model for myocardial ischemia.

Extensive mitochondrial proteome disturbance occurs during the early stages of acute myocardial ischemia.

Mitochondrial malfunction leads to the remodeling of myocardial energy metabolism during myocardial ischemia (MI). However, the alterations to the mitochondrial proteome profile during this period has not yet been clarified. An acute MI model was established by high position ligation of the left anterior descending artery in 8-week-old C57BL/6N mice. After 15 min of ligation, the animals were euthanized, and their hearts were collected. The myocardial ultrastructure was observed using transmission electron microscopy (TEM). The cardiac mitochondrial proteome profile was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analyses. TEM showed that the outer membrane of the mitochondria was dissolved, and the inner membrane (cristae) was corrupted and broken down extensively in the MI group. The mitochondrial membrane potential was decreased. More than 1,700 mitochondrial proteins were identified by LC-MS/MS analysis, and 119 were differentially expressed. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that endopeptidase activity regulation, the mitochondrial inner membrane, oxidative phosphorylation, the hypoxia-inducible factor-1 signaling pathway, the pentose phosphate pathway and the peroxisome proliferator-activated receptor signaling pathway were involved in the pathophysiological process in the early stage of acute MI. Extensive and substantial changes in the mitochondrial proteins as well as mitochondrial microstructural damage occur in the early stages of acute MI. In the present study, the series of proteins crucially involved in the pathways of mitochondrial dysfunction and metabolism were identified. Further studies are needed to clarify the roles of these proteins in myocardial metabolism remodeling during acute MI injury.

Full-length transcriptome analysis reveals the mechanism of acupuncture at PC6 improves cardiac function in myocardial ischemia model

BackgroundThe pathological process of myocardial ischemia (MI) is very complicated. Acupuncture at PC6 has been proved to be effective against MI injury, but the mechanism remains unclear. This study investigated the mechanism that underlies the effect of acupuncture on MI through full-length transcriptome.MethodsAdult male C57/BL6 mice were randomly divided into control, MI, and PC6 groups. Mice in MI and PC6 group generated MI model by ligating the left anterior descending (LAD) coronary artery. The samples were collected 5 days after acupuncture treatment.ResultsThe results showed that treatment by acupuncture improved cardiac function, decreased myocardial infraction area, and reduced the levels of cTnT and cTnI. Based on full-length transcriptome sequencing, 5083 differential expression genes (DEGs) and 324 DEGs were identified in the MI group and PC6 group, respectively. These genes regulated by acupuncture were mainly enriched in the inflammatory response pathway. Alternative splicing (AS) is a post-transcriptional action that contributes to the diversity of protein. In all samples, 8237 AS events associated with 1994 genes were found. Some differential AS-involved genes were enriched in the pathway related to heart disease. We also identified 602 new genes, 4 of which may the novel targets of acupuncture in MI.ConclusionsOur findings suggest that the effect of acupuncture on MI may be based on the multi-level regulation of the transcriptome.

Electroacupuncture improves cardiac function and reduces infarct size by modulating cardiac autonomic remodeling in a mouse model of myocardial ischemia.

Sympathetic and parasympathetic nerve remodeling play an important role in cardiac function after myocardial ischemia (MI) injury. Increasing evidence indicates that electroacupuncture (EA) can regulate cardiac function by modulating the autonomic nervous system (ANS), but little is known about its effectiveness on neural remodeling post-MI. To investigate the role of EA in ANS remodeling post-MI. Adult male C57/BL6 mice were equally divided into the Control (Ctrl), MI and EA groups after generating the MI model by ligating the left anterior descending (LAD) coronary artery. Echocardiography and 2,3,5-triphenyltetrazolium (TTC) staining were employed to evaluate cardiac function and infarct size after EA treatment for five consecutive days. Serum norepinephrine (NE) levels were measured by ELISA to quantify sympathetic activation. Then, ANS remodeling was detected by immunohistochemistry (IHC), RT-qPCR, and Western blotting. Our preliminary findings showed that EA increased ejection fraction and fractional shortening and reduced infarct area after MI injury. Serum NE levels in the EA group were significantly decreased compared with those in the MI group. IHC staining results demonstrated that the density of growth associated protein (GAP)43 and tyrosine hydroxylase (TH) positive nerve fibers in the EA group were decreased with increased choline acetyltransferase (CHAT) and vesicular acetylcholine transporter (VACHT). Meanwhile, the results verified that mRNA and protein expression of GAP43 and TH were significantly inhibited by EA treatment in the MI mice, accompanied by elevated CHAT and VACHT. EA treatment could improve cardiac function and reduce infarct size by modulating sympathetic and parasympathetic nerve remodeling post-MI, thus helping the cardiac ANS reach a new balance to try to protect the heart from further possible injury.

Temporal changes in Egr-1 and c-fos expression in rat models of myocardial ischemia.

The pathological diagnosis of sudden cardiac death caused by myocardial ischemia is a difficult problem. Relevant evidence shows that the expression of Egr-1 and c-fos undergo changes in the early stage of myocardial ischemia, but the detailed temporal variation of them is not clear. Therefore, the aim of this study was to observe the temporal changes in mRNA and protein expression of Egr-1 and c-fos in ischemic myocardium in rats. Sixty-six Sprague-Dawley rats were divided into the control group, the early myocardial ischemia (EMI) group, the sham operated group and the allergy group. The EMI rats were further divided into eight subgroups according to the different time points (30 min and 1, 2, 4, 8, 12, 24, and 48 h) after modeling. The mRNA and protein of Egr-1 and c-fos of each group were detected by real-time quantitative polymerase chain reaction and immunohistochemistry, respectively. In the EMI group, Egr-1 mRNA in ischemic myocardium rose 30 min after ischemia and peaked at 2 h; the plateau was maintained up to 8 h after ischemia, and then returned to the baseline level at 12 h. The c-fos mRNA in ischemic myocardium demonstrated a consistent changing curve with that of Egr-1. The mRNA of Egr-1 and c-fos showed no significant changes in the control group, the sham operated group and the allergy group. Immunohistochemistry showed that Egr-1 protein in the myocardial ischemic area was slightly positive 30 min after ischemia, and then strongly positive at 4 and 8 h, decreased at 12 h, and was negative at 24 h. The changing trends of c-fos protein were almost the same as that of Egr-1. Immunohistochemistry of Egr-1 and c-fos protein were all negative in the control group, the sham operated group and the allergy group. The mRNA and protein expression of Egr-1 and c-fos presented rapid and temporal changes after myocardial ischemia, and this may be helpful in distinguishing sudden death induced by myocardial ischemia from that of allergy.

Systematic Analysis of tRNA-Derived Small RNAs Discloses New Therapeutic Targets of Caloric Restriction in Myocardial Ischemic Rats.

Caloric restriction (CR) is a novel dietary therapy that has a protective effect on myocardial ischemia. However, the mechanisms underlying the therapeutic effect of CR remain unclear. Transfer RNA–derived small RNAs (tsRNAs) are a novel type of short non-coding RNAs that have potential regulatory functions in various physiological and pathological processes. In this study, we explored new therapeutic targets of CR through tsRNA sequencing. Rats were randomly divided into three groups: a normal control group (norm group), isoproterenol (ISO)–induced myocardial ischemic group (MI group), and CR pretreatment plus ISO-induced myocardial ischemic group (CR + MI group). Triphenyl tetrazolium chloride staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, serum creatine kinase (CK) and lactic acid dehydrogenase activity detection kits, and creatine kinase isoenzyme 1 levels were used to measure the degree of myocardial ischemic injury. These indicators of myocardial ischemia were significantly improved in the CR + MI group compared with those in the MI group. In the ischemic myocardial tissue of the MI group, a total of 708 precisely matched tsRNAs were identified, and 302 tsRNAs (fold change >1.5, P < 0.05) were significantly changed when compared with those in the norm group. Furthermore, 55 tsRNAs were significantly regulated by CR pretreatment, among which five tsRNAs (tiRNA-His-GTG-004, tRF-Gly-TCC-018, tRF-Cys-GCA-022, tRF-Lys-CTT-026, tRF-Met-CAT-008) were randomly selected and verified by quantitative real-time polymerase chain reaction. In addition, predictions of target genes and bioinformatics analysis indicated that these tsRNAs may play a therapeutic role through the regulation of macromolecular metabolism. In conclusion, our findings reveal that tsRNAs are potential therapeutic targets for CR pre-pretreatment to improve myocardial ischemic injury. This study provides new ideas for future research on elucidating the mechanisms of CR pretreatment in ameliorating myocardial ischemic injury.

Behavioral and Biochemical Effects of KXS on Postmyocardial Infarction Depression.

BackgroundDepression and coronary heart disease (CHD) often occur together in clinical practice. As a traditional Chinese medicine, Kai-Xin-San (KXS) has been widely used for the treatment of emotion-related disorders. In the present study, we aimed to explore whether KXS had both antidepressive effects and cardioprotective functions in a rat model of myocardial ischemia (MI) with depression.MethodsA total of 50 SD rats were randomly assigned into five groups as follows: normal control (control group), celiac injection of isopropyl adrenaline (ISO) (MI group), depression (depression group), MI+ depression (model group) and MI+ depression treated with intragastric administration of 370 mg/kg KXS (KXS group). MI was induced by subcutaneous injection of 85 mg/kg ISO. Depression was developed by a 7-week chronic mild stress (CMS) challenge. Behavioral test was conducted before and during the experiment. Echocardiography and biochemical analysis were carried out after 7 weeks of CMS challenge.ResultsAfter 7 weeks of experiment, depression-like behaviors were observed in all the groups except for control and KXS groups, and KXS treatment dramatically increased open-field test scores and sucrose consumption (P < 0.01 vs. model group). Echocardiography and biochemical analysis showed that KXS treatment could improve levels of ejection fraction (EF) and fractional shortening (FS), which were reduced by depression and ISO challenge. Meanwhile, KXS treatment significantly decreased the levels of creation kinase MB (CK-MB) and lactate dehydrogenase (LDH), which were increased in the model group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) were increased, while the malondialdehyde (MDA) activity was significantly decreased in the KXS group. Moreover, KXS treatment reduced the levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in myocardial tissue compared with the model group.ConclusionsKXS had antidepressant-like activity and offered cardioprotective effects against ISO-induced myocardial infarction with depression.

Agarwood Alcohol Extract Ameliorates Isoproterenol-Induced Myocardial Ischemia by Inhibiting Oxidation and Apoptosis.

Agarwood is a traditional medicine used for treating some diseases, including painful and ischemic diseases. This study was carried out to investigate the potential cardioprotective effect of the whole-tree agarwood-inducing technique-produced agarwood alcohol extract (WTAAE) on isoproterenol- (ISO-) induced myocardial ischemia (MI) in rats and explore the underlying molecular mechanisms. Compared to the MI group, WTAAE pretreatment significantly improved ST wave abnormal-elevation, mitigated myocardial histological damage; decreased creatinine kinase (CK), lactate dehydrogenase (LDH), alanine transaminase (ALT), and aspartate transaminase (AST) levels; reduced hydrogen peroxide (H2O2) and lipid peroxide (LPO) production; and increased total antioxidant capacity (T-AOC) and catalase (CAT) activities. Moreover, agarwood alcohol extracts (AAEs) markedly enhanced the mRNA levels of Nrf2-ARE pathway, and Bcl-2 reduced the apoptotic Bax family mRNA expressions. In addition, the effect of WTAAE was greater than that of wild agarwood alcohol extract (WAAE) and burning-chisel-drilling agarwood alcohol extract (FBAAE). All of these data indicate that WTAAE exerted the protective effects of MI, and its mechanism was associated with upregulating Nrf2-ARE and suppressing Bcl-2 pathways.

Diosmetin exerts cardioprotective effect on myocardial ischaemia injury in neonatal rats by decreasing oxidative stress and myocardial apoptosis.

Myocardial injury caused by the myocardial ischaemia (MI) is still a troublesome condition in the clinic, including apoptosis, oxidative stress and inflammation. Diosmetin inhibits the cellular apoptosis and inflammatory response and enhances antioxidant activity. So, this study was designed to investigate the cardioprotective effects of diosmetin on MI model neonatal rats. Forty Sprague Dawley (SD) rats 7 days old were randomly divided into five groups. Four groups of rats received diosmetin (50, 100, and 200 mg/kg) or vehicle (MI group) after ischaemia. Another group received vehicle without ischaemia to serve as a control group. Rats were pretreated with diosmetin intraperitoneally for 7 days and intoxicated with isoproterenol (ISO, 85 mg/kg, sc) on the last 2 days. The expression of apoptotic molecules, myocardial systolic function index, antioxidant enzymes and myocardial enzyme was analyzed. Compared with the control group, the proliferation marker proteins of Ki67 were increased significantly (P < .05), the MI group significantly increased the cardiac apoptosis, oxidative stress and myocardial enzymes, and weakened myocardial contractility. The levels of p‐P65/P65 were increased significantly (P < .05) with decreased p‐AKT/AKT and p‐Nrf2/Nrf2 (P < .05). Nevertheless, pretreatment with diosmetin reversed these changes, especially high‐dose group. In summary, diosmetin has significant potential as a therapeutic intervention to ameliorate myocardial injury after MI and provides the rationale for further clinical studies.