Degree Of Myocardial Ischemia Research Articles

Myocardial viability under various ischemic burdens in chronic total occlusions: A stress-cardiac magnetic resonance study

ObjectivesThis study aimed to analyze each myocardial segment's ischemic burden, scarring, function, and viability by late gadolinium enhancement (LGE) imaging and stress-MRI using adenosine. Materials and methodsSemi-quantitative and qualitative parameters of myocardial segments were obtained by stress-MRI. Moreover, segments without perfusion defect were defined as the no ischemic group, segments with a perfusion defect of ≤50% were defined as a low ischemic burden group, and segments with a perfusion defect of >50% were defined as a high ischemic burden group. “Segmental wall thickening (SWT)” was defined as the absolute difference between the end-diastolic and end-systolic wall thickness. Finally, viability was defined by dysfunctional myocardium (<3 ​mm segmental wall thickening [SWT]) and ≤50% late gadolinium enhancement (LGE). ResultsA total of 445 segments in the CTO territory were analyzed, scar tissue was found in the CTO territory, with LGE evident in 18.2% of CTO segments totaling >50%. Among the different ischemic burden groups, there were significant differences in LGE volume (p ​< ​0.01), and the trend of SWT was consistent with the degree of myocardial ischemia. The incidence of ≤50% LGE and viable myocardium was higher in segments of the no ischemia and low ischemic burden groups. However, there was no significant difference in the incidence of dysfunctional myocardial segments among the three groups (P ​> ​0.05). ConclusionsStress MRI parameters can accurately and detailly assess myocardial viability and function, so multi-parameter joint assessment of CTO patients by stress MRI may help in treatment decisions.

Pathological Turbulence of the Heart Rhythm and Activation of the Antinociceptive System as Predictors of the Complicated Course of Silent Myocardial Ischemia in Patients with Post Infarction Cardiosclerosis According to the Data of Long-term Observation

To date, the issues of evaluating the course of silent myocardial ischemia (SMI) after a myocardial infarction (MI) taking into account risk factors (RF), evaluating the pathological turbulence of the heart rhythm, the state of activation of the body’s antinociceptive system, which necessitates an in-depth study of this pathology, remain unresolved, as well as new differentiated approaches to the treatment and rehabilitation of the modern category of patients. The objective: to analyze the features of the SMI course in patients with post-infarction cardiosclerosis depending on the RF. Identification of the interdependence between the degree of activation of the sympathoadrenal system and the features of the SMI course in patients with post-infarction cardiosclerosis, as well as the prognostic value for assessing the severity of the course of the disease. Materials and methods. The research was performed on the basis of the Ivano-Frankivsk Regional Clinical Cardiology Center (Ukraine). 154 patients with a silent form of coronary artery disease, which occurred in people with post-infarction cardiosclerosis, were examined. The diagnostic criteria were: episodes of SMI verified with the help of HM ECG and a test with dosed physical load. Results. Significant deviation of the ST segment which was detected during Holter monitoring of the ECG (HM ECG) in patients with SMI episodes does not mean that the absence of pain sensations in the presence of efferent nociceptive stimulation is a sign of the absence of ischemia and does not indicate an easier course of SMI compared to clinically manifest forms of CHD. The average concentration of β-endorphins in patients with lipid metabolism disorders was 4.01±0.02 ng/ml, in the presence of diabetes mellitus this indicator was equal to 4.68±0.03 ng/ml (р&lt;0.01), and in persons with concomitant arterial hypertension it was 4.91±0.02 ng/ml (р&lt;0.05). In subjects with two or more RFs, the similar indicator was the highest and amounted to 5.73±0.03 ng/ml (р&lt;0.01). The point-biserial correlation coefficient was equal to 0.61 (р&lt;0.05), which indicates a sufficiently high probability of the influence of the processes of activation of the antinociceptive system on the risk of myocardial infarction and unstable angina. Conclusions. It has been proven that the presence of postinfarction cardiosclerosis, type 2 diabetes mellitus, dyslipidemia, and arterial hypertension should be considered as factors that increase the risk of complications of coronary artery disease in patients with SMI. In the painless form of CHD, there is a probable increase in β-endorphins in the blood, which indicates the presence of pronounced afferent nociceptive stimulation, the intensity of which depends on the degree of myocardial ischemia. It has been proven that an increase of β-endorphins levels is associated with an increase in the risk of a complicated course of coronary heart disease in patients with silent myocardial ischemia. The presence in patients with SMI of myocardial ischemia, pathological turbulence of the heart rhythm, and activation of the antinociceptive system are extremely important for understanding the main links of the course of SMI and make it possible to base the approach to the therapy of such patients on a differentiated system algorithm that takes into account the discrepancy between the clinical manifestations of the disease and its real impact on coronary perfusion and the condition of the vascular wall.

Myocardial ischemia simulation based on a multi-scale heart electrophysiology model.

Myocardial ischemia, caused by insufficient myocardial blood supply, is a leading cause of human death worldwide. Therefore, it is crucial to prioritize the prevention and treatment of this condition. Mathematical modeling is a powerful technique for studying heart diseases. The aim of this study was to discuss the quantitative relationship between extracellular potassium concentration and the degree of myocardial ischemia directly related to it. A human cardiac electrophysiological multiscale model was developed to calculate action potentials of all cells simultaneously, enhancing efficiency over traditional reaction-diffusion models. Contrary to the commonly held view that myocardial ischemia is caused by an increase in extracellular potassium concentration, our simulation results indicate that level 1 ischemia is associated with a decrease in extracellular potassium concentration. This unusual finding provides a new perspective on the mechanisms underlying myocardial ischemia and has the potential to lead to the development of new diagnostic and treatment strategies.

The Role of Fluid Mechanics in Coronary Atherosclerotic Plaques: An Up-to-Date Review.

Most acute coronary syndromes are due to a sudden luminal embolism caused by the rupturing or erosion of atherosclerotic plaques. Prevention and treatment of plaque development have become an effective strategy to reduce mortality and morbidity from coronary heart disease. It is now generally accepted that plaques with thin-cap fibroatheroma (TCFA) are precursors to rupturing and that larger plaques and high-risk plaque features (including low-attenuation plaque, positive remodeling, napkin-ring sign, and spotty calcification) constitute unstable plaque morphologies. However, plaque vulnerability or rupturing is a complex evolutionary process caused by a combination of multiple factors. Using a combination of medicine, engineering mechanics, and computer software, researchers have turned their attention to computational fluid mechanics. The importance of fluid mechanics in pathological states for promoting plaque progression, inducing plaque tendency to vulnerability, or even rupture, as well as the high value of functional evaluation of myocardial ischemia has become a new area of research. This article reviews recent research advances in coronary plaque fluid mechanics, aiming to describe the concept, research implications, current status of clinical studies, and limitations of fluid mechanic's characteristic parameters: wall shear stress (WSS), axial plaque shear (APS), and fractional flow reserve (FFR). Previously, most computational fluid dynamics were obtained using invasive methods, such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT). In recent years, the image quality and spatial resolution of coronary computed tomography angiography (CCTA) have greatly improved, making it possible to compute fluid dynamics by noninvasive methods. In the future, the combination of CCTA-based anatomical stenosis, plaque high-risk features, and fluid mechanics can further improve the prediction of plaque development, vulnerability, and risk of rupturing, as well as enabling noninvasive means to assess the degree of myocardial ischemia, thereby providing an important aid to guide clinical decision-making and optimize treatment.

Retracted: Serum IMA and LP-PLA2 Levels in Patients with Coronary Heart Disease and Their Correlation with the Degree of Myocardial Ischaemia and Their Diagnostic Value.

[This retracts the article DOI: 10.1155/2022/1698315.].

Stress Cardiovascular Magnetic Resonance Imaging for the Detection of Coronary Artery Disease.

Stress cardiovascular magnetic resonance (CMR) imaging has received extensive validation for the assessment of ischemic heart disease. Without ionizing radiation exposure, it offers in-depth information regarding cardiac structure and function, presence and degree of myocardial ischemia and myocardial viability. When compared to other imaging modalities, it has demonstrated excellent sensitivity and specificity in detecting functionally relevant coronary artery stenosis, as well as strong prognostic value in clinical risk stratification. The current scientific data support a greater expansion of stress CMR. This review investigates the current stress CMR techniques and protocols, as well as its relevance in diagnosis and prognosis of coronary artery disease.

EFFECTS OF TRANSPLANTATION OF MSCS AND PANCREATIC BETA CELLS ON METABOLIC PARAMETERS OF BLOOD PLASMA IN RATS WITH MYOCARDIAL INFARCTION WITH UNDERLYING DIABETES MELLITUS

The purpose of this work was to study the role of transplantation of mesenchymal stem cells (MSCs) and pancreatic beta cells (BCs) in metabolism of rats with diabetes mellitus (DM) and myocardial infarction (MI). The animals formed 4 groups, 24 in each: control group - healthy Wistar-Kyoto animals, which served as the norm for the studied parameters; group 1 in which animals with diabetes mellitus had a myocardial infarction simulated by ligation of the left gastric artery after the first branch; group 2 – rats with the model of MI and DM which, on the day 2 after the modeling, had transplantation of rat mesenchymal stem cells taken from the bone marrow of tubular bones; group 3 – rats with DM+MI model which received transplantation of MSCs and rat pancreatic BCs on the day 2 after the modeling. We dynamically studied the activity of aspartate aminotransferase enzymes, creatine kinase-MB, blood plasma lactate dehydrogenase, and haptoglobin and ceruloplasmin proteins. The study revealed that cardiomyoplasty with MSCs caused a positive metabolic effect. MSC transplantation is accompanied by a decrease in the activity of ADA and LDH enzymes in the damaged myocardium, which indirectly indicates an increase in the energy balance of energy-forming substrates and a decrease in the degree of myocardial ischemia. A decrease in the accumulation of lipid peroxidation products and the tension of the non-enzymatic antioxidant protection is a good prognostic criterion for the restoration of the functional activity of the damaged myocardium. The transplantation of a mixed culture of MSCs and pancreatic BCs makes it possible to fully compensate for carbohydrate metabolism, to achieve the best performance in the studied groups in terms of lipid peroxidation regulation and activation of the antioxidant system.

Influence of trimetazidine on myocardium energy balance during chemotherapy with doxorubicin and cyclophosphamide

Aim of the study was to assess the degree of myocardial ischemia in rats on chronic in vivo model, with a simultaneous assessment of justification for the use of trimetazidine. Material and methods. The object of the study was 120 male inbred Wistar rats, randomly divided into 4 equal groups: group 1 – control (administration of 0.9% sodium chloride solution 3 times a week); group 2 – simulation of the AC chemotherapy regimen by intraperitoneal administration of doxorubicin hydrochloride at a single dose of 2.5 mg/kg and cyclophosphamide monohydrate at a single dose of 25 mg/kg 3 times a week; group 3 – simulation of the AC chemotherapy regimen with additional administration of trimetazidine dihydrochloride daily by intragastric gavage at a single dose of 3.0 mg/kg; group 4 – administration of trimetazidine dihydrochloride. The study has been carried out for two weeks. An Olympus IX51 microscope was used to assess the changes. Staining was carried out by the HBFP method (hematoxylin + basic fuchsin + picronic acid). Results and discussion. In group 2, on the background of AC chemotherapy, the level of fuchsinophilia in myocardial tissue was 87.2 and 90.9 % higher (p &lt; 0.05) than in groups 1 and 4, respectively, the specific area of damage was 170.8 and 167. 5 %, respectively (p &lt; 0.05). In group 3, the severity of fuchsinophilia and the specific area of myocardial damage were statistically significantly less (by 26.3 and 36.5 %, p &lt; 0.05) than in group 2. Conclusions. Trimetazidine is a pathogenetically effective drug that protects the myocardium from damage associated with AC chemotherapy.

Serum IMA and LP-PLA2 Levels in Patients with Coronary Heart Disease and Their Correlation with the Degree of Myocardial Ischaemia and Their Diagnostic Value.

Purpose To measure serum levels of ischaemia-modified albumin (IMA) and lipoprotein-associated phospholipase A2 (LP-PLA2) in patients with coronary heart disease (CHD) and to analyse their correlation with the degree of myocardial ischaemia and their diagnostic value. Methods A sample of 150 patients diagnosed with CHD by coronary angiography in our hospital from March 2019 to September 2021 was taken as the CHD group. The patients were divided into acute myocardial infarction (AMI) group (n = 52), unstable angina pectoris (UAP) group (n = 54), and stable angina pectoris (SAP) group (n = 44) according to the degree of myocardial ischaemia, and then 50 healthy physical examination patients were selected as the health group during the same period. Serum C-reactive protein (CRP), interleukin-6 (IL-6), IMA, and LP-PLA2 levels were measured in each group separately. Multiple ordered logistic regression was used to analyse the factors influencing the degree of myocardial ischaemia in patients with CHD. Pearson correlation was used to analyse the correlation between serum IMA, LP-PLA2 levels and serum CRP, IL-6 levels in CHD patients. The diagnostic value of IMA alone, LP-PLA2 alone, and in combination for CHD was analysed using receiver operating characteristic (ROC) curves. Results In terms of serum CRP, IL-6, IMA, and LP-PLA2 levels, the CHD group was higher than the health group, the AMI and UAP groups were higher than the SAP and health groups, and the AMI group was higher than the UAP group (P < 0.05). Multiple ordered logistic regression analysis showed that serum CRP, IL-6, IMA, and LP-PLA2 levels were all independent influences on the degree of myocardial ischaemia in patients with CHD (P < 0.05). Pearson correlation analysis showed a positive correlation between serum IMA, LP-PLA2 levels and serum CRP, IL-6 levels in CHD patients (P < 0.001). The area under curve (AUC) for serum IMA levels to predict myocardial ischaemia in patients with CHD was 0.754 (95% CI: 0.684–0.825), with a sensitivity of 61.3% and specificity of 84.0% when the best cut-off value was 0.453; the AUC for serum LP-PLA2 levels to predict myocardial ischaemia in patients with CHD was 0.747 (95% CI: 0.681–0.813), with a sensitivity of 62.0% and specificity of 82.0% when the optimal cut-off value was 0.440; and the AUC of IMA + LP-PLA2 for predicting myocardial ischaemia in patients with CHD was 0.892 (95% CI: 0.847–0.938), with a sensitivity of 86.7% and specificity of 80.0% when the optimal cut-off value was 0.667. The specificity was 80.0%. Conclusions Serum IMA and LP-PLA2 levels are elevated in patients with CHD. Serum IMA and LP-PLA2 levels are closely related to the degree of myocardial ischaemia and its inflammatory level, and the combination of IMA + LP-PLA2 can improve the diagnosis efficacy of myocardial ischaemia in CHD patients.

Non-Invasive Quantification of Fraction Flow Reserve Based on Steady-State Geometric Multiscale Models.

Background: The underuse of invasive fraction flow reserve (FFR) in clinical practice has motivated research towards its non-invasive prediction. The early attempts relied on solving the incompressible three-dimensional Navier–Stokes equations in segmented coronary arteries. However, transient boundary condition has a high resource intensity in terms of computational time. Herein, a method for calculating FFR based on steady-state geometric multiscale (FFRSS) is proposed. Methods: A total of 154 moderately stenotic vessels (40–80% diameter stenosis) from 136 patients with stable angina were included in this study to validate the clinical diagnostic performance of FFRSS. The method was based on the coronary artery model segmented from the patient’s coronary CTA image. The average pressure was used as the boundary condition for the inlet, and the microcirculation resistance calculated by the coronary flow was used as the boundary condition for the outlet to calculate the patient-specific coronary hyperemia. Then, the flow velocity and pressure distribution and the FFRss of each coronary artery branch were calculated to evaluate the degree of myocardial ischemia caused by coronary stenosis. Also, the FFRSS and FFRCT of all patients were calculated, and the clinically measured FFR was used as the “gold standard” to verify the diagnostic performance of FFRSS and to compare the correlation between FFRSS and FFRCT. Results: According to the FFRSS calculation results of all patients, FFRSS and FFR have a good correlation (r = 0.68, p < 0.001). Similarly, the correlation of FFRSS and FFRCT demonstrated an r of 0.75 (95%CI: 0.67–0.72) (p < 0.001). On receiver-operating characteristic analysis, the optimal FFRSS cut point for FFR≤0.80 was 0.80 (AUC:0.85 [95% confidence interval: 0.79 to 0.90]; overall accuracy:88.3%). The overall sensitivity, specificity, PPV, and NPV for FFRSS ≤0.80 versus FFR ≤0.80 was 68.18% (95% CI: 52.4–81.4), 93.64% (95% CI: 87.3–97.4), 82.9%, and 91.1%, respectively. Conclusion: FFRSS is a reliable diagnostic index for myocardial ischemia. This method was similar to the closed-loop geometric multiscale calculation of FFR accuracy but improved the calculation efficiency. It also improved the clinical applicability of the non-invasive computational FFR model, helped the clinicians diagnose myocardial ischemia, and guided percutaneous coronary intervention.

Is It ST-Segment-Elevation Myocardial Infarction?

A 76-year-old man presented with acute-onset chest pain and dyspnea. He had a history of coronary artery disease, ischemic cardiomyopathy (left ventricular ejection fraction, 25%), recent non-ST-segment-elevation myocardial infarction (NSTEMI), and stenting of the left anterior descending coronary artery (LAD) one month before the current presentation. Soon thereafter, he underwent stenting of the left main coronary artery (LMCA), obtuse marginal branch (OMB), and left circumflex coronary artery. His chest pain subsided soon after arrival at the emergency department. His cardiac troponin I level was 22 ng/mL (normal level, &lt;0.03 ng/mL), and his brain natriuretic peptide level was 841 pg/mL (normal level, &lt;100 pg/mL). Figure 1 shows his electrocardiogram (ECG).What is the diagnosis?C) STEMI due to first OMB or ramus intermedius occlusionThe ECG shows sinus rhythm, mild ST-segment elevation (STE) with T-wave inversion in lead aVL, ST-segment depression with positive T waves in leads II, III, aVF, and V3 through V6, and an isoelectric ST segment in leads I and V1 through V2. The Fourth Universal Definition of Myocardial Infarction1 says, “More profound ST-segment shifts or T-wave inversions involving multiple leads/territories are associated with a greater degree of myocardial ischaemia, and a worse prognosis. For example, ST-segment depression ≥1 mm in 6 leads, which may be associated with STE in lead aVR or lead V1 and hemodynamic compromise, is suggestive evidence of multivessel disease or left main disease” (eliminating answer A). This is considered a high-risk ECG pattern for which invasive intervention within 2 hours is recommended, in accordance with the 2020 European Society of Cardiology guidelines for managing acute coronary syndromes without persistent STE.2 Our patient's ECG shows ST-segment depression in 7 leads but no significant STE in lead aVR or V1. In contrast, STE with negative T waves is seen in lead aVL.Patients with a nonischemic early repolarization pattern can have STE in lead aVL. However, the T waves are usually positive, and there is often a J-point notch. The pattern here suggests a reperfused or more advanced stage of STEMI,3 and the patient's clinical presentation (symptom resolution after hospital arrival) supports this diagnosis.New STE in 2 contiguous leads is necessary for the diagnosis of STEMI.1 However, this is an epidemiologic (not pathophysiologic) criterion, to minimize false-positive diagnosis. Acutely occluded arterial branches may cause STE in only one lead with diffuse ST-segment depression.4 The STE in leads aVL and V2 through V5 is caused by LAD occlusion proximal to the first diagonal branch (eliminating answer B),4 and STE in leads aVL and V2 without STE in leads V3 through V5 suggests an occluded first diagonal branch. The ST-segment depression in the anterolateral and inferior leads is incompatible with the typical presentation of takotsubo cardiomyopathy (answer D). The STE in lead aVL, incompatible with ischemic cardiomyopathy (answer E), is accompanied by ST-segment depression in lead V2, suggesting obstruction of the first OMB. Our patient had an isoelectric ST segment in lead V2, so the differential diagnosis is an occluded OMB or ramus intermedius.4 A coronary angiogram on the second day of admission showed subacute thrombotic occlusion of the first OMB (Fig. 2, arrow), and stenting restored patent flow.Disclosures: NoneFunding/support: None

Role of fractional flow reserve for invasive functional evaluation in surgical myocardial revascularization: available evidence and state of the art

Fractional flow reserve (FFR) is the ratio of distal to proximal pressure during maximal hyperemia and indirectly estimates the blood flow across a stenotic coronary artery and the related degree of myocardial ischemia. Several studies have investigated the role of FFR in the setting of percutaneous myocardial revascularization and further research is ongoing. However, current evidence on FFR-guided surgical myocardial revascularization is controversial and limited. The main scientific interest is to clarify whether FFR-guided coronary artery bypass surgery is associated with clinical benefits in terms of mortality, myocardial infarction, major adverse cardiovascular events, minimally invasive surgical access compared with sternotomy and off-pump surgery. Furthermore some data suggest that conduit selection for coronary artery bypass grafting and surgical technique might be affected by FFR value. The aim of this article is to review the most recent available evidence about FFR-guided coronary artery bypass grafting and to discuss clinical implications and future perspectives.

Thrombolytic effects of recombinant staphylokinase on coronary thrombosis in miniature pigs

To evaluate the thrombolytic effects of recombinant staphylokinase and compare it with those of recombinant streptokinase. Thirty Chinese experimental miniature pigs were divided into five groups, namely, solvent control group, positive drug control group and three recombinant staphylokinase groups, six in each group. The thrombus of coronary artery was formed by surgical thoracotomy and direct current stimulation in anesthetized animals. Intravenous administration was started after the thrombus of coronary artery was formed for 30 minutes, and the method of first injection and then constant speed infusion by peristaltic pump was used. The solvent control group was injected intravenously with solvent, the positive drug control group was given recombinant streptokinase 4 mg·kg-1 intravenously, and the three recombinant staphylokinase groups were given recombinant staphylokinase at the doses of 4, 2 and 1 mg.kg-1 intravenously. The volume of intravenous injection was 5 ml, which was completed within 1 min, the speed of infusion was 0.5 ml·min-1, which was completed within 60 min, and the animals were sacrificed 120 minutes later. Before and 30, 60 and 120 min after administration, the venous blood samples were collected. At the end of the experiment, the coronary artery segments of the thrombosis site were taken, and the euglobulin dissolution time (ELT), blood fibrinogen content (FBG), fibrinogen degradation product (FDP) and wound bleeding volume were measured respectively. The coronary thrombolysis rate, myocardial ischemia degree and ischemia range were measured. Compared with the solvent control group, ELT in the experimental group was significantly shortened (P＜0.05 or P＜0.01), FBG degradation in a few experimental animals was more than 20%, FDP was significantly increased (P＜0.05 or P＜0.01), and there was no significant effect on blood pressure and heart rate of small pigs. Compared with the control group, the maximum thrombus area was decreased by 34.3% and 15.4% (P＜0.05) in the high and middle dose groups of the experimental group. Compared with the same dose of recombinant streptokinase, recombinant staphylokinase had stronger thrombolytic effect (P＜0.05 or P＜0.01) on the coronary thrombus caused by electrical stimulation, less bleeding side effects and the same effect on the degree and range of myocardial infarction as recombinant streptokinase. Compared with recombinant streptokinase, recombinant staphylokinase has faster thrombolysis speed, higher fibrin specificity and less bleeding side effects. In general, 2 mg.kg-1 recombinant staphylokinase has better efficacy and safety.

Shenlian Extract Against Myocardial Injury Induced by Ischemia Through the Regulation of NF-κB/IκB Signaling Axis.

Ischemic heart disease (IHD), caused predominantly by atherosclerosis, is a leading cause of global mortality. Our previous studies showed that Shenlian extract (SL) could prevent the formation of atherosclerosis and enhance the stability of atherosclerotic plaques. To further investigate the protective effects of SL on myocardial ischemic injury and its possible mechanisms, anesthetized dogs, ex vivo rat hearts, and H9c2 cardiomyocytes were used as models. The results showed that SL had a significant protective effect on the anesthetized dog ligating coronary artery model, reduced the degree of myocardial ischemia (Σ-ST), and reduced the scope of myocardial ischemia (N-ST). Meanwhile, SL alleviated ischemic reperfusion damage in ex vivo rat hearts with improved LVEDP and ± dp/dtmax values of the left ventricle. SL reduced the pathological changes of LDH, IL-1β, MDA, and NO contents, all of which are related to the expression of NF-κB. Further analysis by Bio-Plex array and signal pathway blocker revealed that the phosphorylation of IκB was a key factor for SL to inhibit myocardial ischemic injury, and the regulation of SL on IκB was primarily related to degradation of the IκB protein. These results provided dependable evidence that SL could protect against myocardial ischemic injury through the NF-κB signaling pathway.

Experimental study on "ischemic memory" of myocardium with different ischemic degrees by 18F-FDG PET/CT.

Glucose metabolism and ranges of ischemic cardiomyocytes in model rats under fasting or feeding were compared by 18F-FDG PET/CT, respectively, to investigate the changes of glucose metabolism after myocardial reperfusion, and to determine time window of myocardial "ischemic memory" under feeding. The ischemic-reperfusion model rats were established by ligating the left anterior descending coronary artery of rats. In fasting-feeding experiment, long-ischemia rats (n = 10) under fasting or feeding were subjected to 18F-FDG PET/CT at 24h after modeling. Ischemic myocardium range and glucose metabolism were compared by calculating volume of interest (VOI), and mean standard uptake value (SUVmean). Under feeding, model rats in short, intermediate and long-ischemia groups were subjected to 18F-FDG PET/CT at 24, 48, and 72h and long-ischemia rats were also subjected to 18F-FDG PET/CT at 96h, and VOI and SUVmean were calculated and compared. (1) Under fasting, myocardial ischemic area of model rats showed "focal" 18F-FDG uptake, while "focal" 18F-FDG uptake defect appeared in the same area of myocardium under feeding and the difference was not statistically significant (P > 0.05). (2) Under feeding, PET myocardial images of model rats in three groups at 24h and 48h showed that there was an 18F-FDG uptake defect area near the apex of left ventricular wall. The images at 72h showed that there was no abnormal 18F-FDG uptake defect area in short and intermediate-ischemia groups, while 18F-FDG uptake defect area in long-ischemia group disappeared at 96h. Variance analysis of repeated measures was performed for data of three groups, which showed there was statistical significance between myocardial ischemia degree and "ischemic memory" time window (P < 0.05), and also between myocardial ischemia degree and difference of myocardial defect volume (P < 0.05). Under feeding, recent myocardial ischemia could be diagnosed by 18F-FDG PET/CT. Under feeding, "ischemic memory" time window for short and intermediate-myocardial ischemia was at least 48h and for long ischemia was at least 72h. This study suggested that as the degree of myocardial ischemia increased, "ischemic memory" time window also extended.

Association between serum lipoprotein-associated phospholipase A2, ischemic modified albumin and acute coronary syndrome: a cross-sectional study.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a newly emerging biomarker with strong pro-inflammatory effects, and is an independent risk predictor of atherosclerotic plaque rupture and thrombosis. In addition, ischemic modified albumin (IMA) is another important marker for the evaluation of myocardial ischemia, and has been approved by the U.S. Food and Drug Administration. The objective of this study was to investigate serum Lp-PLA2 and IMA in the early diagnosis, progression and prognosis of acute coronary syndrome (ACS). Serum Lp-PLA2 and IMA were detected using an AU5800 automatic biochemical analyzer in samples from 180 patients with ACS [n = 60 with unstable angina pectoris (UA), n = 56 with non-ST segment elevation myocardial infarction (NSTEMI), and n = 64 with ST segment elevation myocardial infarction (STEMI)] and 60 healthy control subjects. The relationship between Lp-PLA2 and IMA with Gensini score and the number of coronary artery lesions was explored, and logistic regression was conducted to identify risk factors for major adverse cardiovascular events (MACE). Serum Lp-PLA2 and IMA were significantly higher in all ACS subgroups compared to the control group (P < 0.05), were positively associated with the severity of ACS based on the Gensini score (P < 0.05), and were significantly higher in patients with double- and triple-vessel lesions compared to those with single-vessel lesions and healthy controls (P < 0.05). Logistic regression identified Lp-PLA2, IMA, and troponin I levels as independent risk factors for MACE. Lp-PLA2 and IMA were predictive of the degree of myocardial ischemia in patients with ACS, and may provide important clinical significance for the early diagnosis of ACS and the choice of treatment strategy.

Effect of isoflurane on myocardial ischemia-reperfusion injury through the p38 MAPK signaling pathway.

To investigate the effect of isoflurane on myocardial ischemia-reperfusion injury through the p38 mitogen-activated protein kinase (MAPK) signaling pathway. A total of 36 specific-pathogen-free (SPF) Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12) and isoflurane group (n=12). In model group and isoflurane group, the myocardial ischemia-reperfusion injury model was established via the ligation of left anterior descending coronary artery (ischemia for 30 min and reperfusion for 3 h). In sham group, the left anterior descending coronary artery was not ligated, but the chest was opened and threaded using the same method. After ischemia, the rats in isoflurane group were inhaled with isoflurane. The cardiac function of rats in each group was detected before ischemia (T0) and once every 2 h after reperfusion (T1-T4) for a total of 5 times, and the cardiac function indexes included ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP). After the rats were executed, the myocardial infarction tissues were taken for hematoxylin-eosin (HE) staining and 2,3,5-triphenyltetrazolium chloride (TTC) staining to observe the morphological changes in tissues and the degrees of myocardial ischemia and infarction. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in myocardial cells in the infarction site in each group were detected using the MDA and SOD kits. Moreover, the expression levels of related proteins in the p38 MAPK signaling pathway in myocardial cells in the infarction site were detected via Western blotting. In model group, the cardiac function was significantly damaged (p<0.01), there was significant pathological damage in the myocardium, the area of myocardial infarction was significantly increased (p<0.01), the MDA content was significantly increased (p<0.01), the SOD activity declined obviously (p<0.01), and the expression levels of p-p38 and p-tau protein were significantly increased (p<0.01) compared with those in control group. After intervention with isoflurane, the cardiac function of rats was significantly improved (p<0.01), the pathological damage in myocardial tissues was alleviated, the area of myocardial infarction was reduced (p<0.01), the MDA content declined (p<0.01), the SOD activity was increased (p<0.01), and the expression levels of p-p38 and p-tau protein were decreased (p<0.01). Isoflurane can, through inhibiting the p38 MAPK signaling pathway, effectively protect the cardiac function of rats from myocardial ischemia-reperfusion injury, reduce the area of myocardial infarction, alleviate the pathological damage in myocardial cells and reduce the oxidative stress response.

Ischemic Stroke Increases Heart Vulnerability to Ischemia-Reperfusion and Alters Myocardial Cardioprotective Pathways.

Background and Purpose- For years, the relationship between cardiac and neurological ischemic events has been limited to overlapping pathophysiological mechanisms and common risk factors. However, acute stroke may induce dramatic changes in cardiovascular function. The aim of this study was to evaluate how prior cerebrovascular lesions affect myocardial function and signaling in vivo and ex vivo and how they influence cardiac vulnerability to ischemia-reperfusion injury. Methods- Cerebral embolization was performed in adult Wistar male rats through the injection of microspheres into the left or right internal carotid artery. Stroke lesions were evaluated by microsphere counting, tissue staining, and assessment of neurological deficit 2 hours, 24 hours, and 7 days after surgery. Cardiac function was evaluated in vivo by echocardiography and ex vivo in isolated perfused hearts. Heart vulnerability to ischemia-reperfusion injury was investigated ex vivo at different times post-embolization and with varying degrees of myocardial ischemia. Left ventricles (LVs) were analyzed with Western blotting and quantitatve real-time polymerase chain reaction. Results- Our stroke model produced large cerebral infarcts with severe neurological deficit. Cardiac contractile dysfunction was observed with an early but persistent reduction of LV fractional shortening in vivo and of LV developed pressure ex vivo. Moreover, after 20 or 30 minutes of global cardiac ischemia, recovery of contractile function was poorer with impaired LV developed pressure and relaxation during reperfusion in both stroke groups. Following stroke, circulating levels of catecholamines and GDF15 (growth differentiation factor 15) increased. Cerebral embolization altered nitro-oxidative stress signaling and impaired the myocardial expression of ADRB1 (adrenoceptor β1) and cardioprotective Survivor Activating Factor Enhancement signaling pathways. Conclusions- Our findings indicate that stroke not only impairs cardiac contractility but also worsens myocardial vulnerability to ischemia. The underlying molecular mechanisms of stroke-induced myocardial alterations after cerebral embolization remain to be established, insofar as they may involve the sympathetic nervous system and nitro-oxidative stress.

Role of Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway in cardioprotection of exercise preconditioning.

To investigate the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the cardioprotective mechanisms of exercise preconditioning (EP). Eighty male Sprague-Dawley (SD) rats were randomized into the Group control, Group EE, Group EP+EE, Group EP+EE+AG, and Group EE+AG. By using 3 days of intermittent treadmill exercise, this study established the EP animal model. Rats were subjected to run to exhaustion on the treadmill at 30 m/min with 0% grade as an exhaustive exercise (EE) protocol. The myocardial injury induced by exhaustive exercise was produced 24 h after EP. JAK2 inhibitor (AG490, 3 mg/kg) was injected before EP. Serum cardiac troponin I (cTnI) levels and hematoxylin basic fuchsine picric acid (HBFP) staining were used to observe the degree of myocardial ischemia. TUNEL, Bcl2, and cleaved caspase-3 levels were used to evaluate the change of myocardial apoptosis. Moreover, the phosphorylations of JAK2 and STAT3 were analyzed as possible mechanisms that might explain the EP-induced cardioprotection. EP significantly attenuated the exhaustive exercise-induced myocardial ischemia injury, associated with lower serum cTnI levels, decreased myocardial infarct area, reduced myocardial apoptosis, increased Bcl2 level, decreased cleaved caspase-3 level, and the increased phosphorylations of JAK2 and STAT3. Treatment with AG490 abolished the cardioprotective effects and the enhanced phosphorylations of JAK2 and STAT3 induced by EP. EP plays its cardioprotective role via activating the JAK2/STAT3 signaling pathway, reducing the apoptosis of myocardial cells and alleviating myocardial ischemia injury.

Abstract 8: Association Between Abnormalities in Myocardial Perfusion and Patient-reported Angina Among Patients With Known Coronary Artery Disease: PET vs. SPECT Comparison

Background: Although the burden of angina would be expected to be intricately linked with the degree of myocardial ischemia, prior work with stress echocardiography and SPECT myocardial perfusion imaging (MPI) have shown these two measures to be poorly correlated. We examined the association of positron emission tomography (PET) MPI, which can more accurately characterize myocardial ischemia, with angina. Methods: Patients with known CAD who were referred for a clinically-indicated vasodilator MPI at Saint Luke’s Hospital (Kansas City, MO) were included. All patients underwent both SPECT and PET MPI and completed the Seattle Angina Questionnaire (SAQ) at the time of MPI. SAQ angina frequency (AF) and physical limitation (PL) scores were compared across the spectrum of ischemic burden (no ischemia, &lt;5, 5-10 and &gt;10% ischemic myocardium) with PET and SPECT. Results: Among 322 patients with CAD undergoing MPI (mean age 66.3 ± 9.7 years; 64.9% men), mean SAQ AF and PL scores were 78.5 ± 19 and 83.3 ± 19.8, respectively. A total of 72 patients (44.7%) with PET and 67 (41.6%) with SPECT had at least mild ischemia on MPI. There was no association with burden of angina by SAQ AF or PL scores and degree of ischemia by PET or SPECT MPI (Figure). Conclusion: We found no association between patient-reported angina and the burden of ischemia, regardless of the modality used. These findings suggest that other complex, multi-system pathways likely impact perception of pain and description of angina in patients with CAD, and that direct measurement of patient-reported symptoms needs to supplement physiologic assessment of ischemia.