Establishment of nonobstructive coronary microcirculatory disorders in rabbits using three established methods and a comparative study.

To compare the merits and drawbacks of three approaches for establishing a rabbit model of nonobstructive coronary microcirculatory disease, namely, open thoracic subtotal ligation of coronary arteries, ultrasound-guided cardiac microsphere injection, and sodium laurate injection. New Zealand rabbits were allocated to four groups: a normal group (Blank group), an Open-chest group (Open-chest), a microsphere group (Echo-M), and a sodium laurate group (Echo-SL), each comprising 10 rabbits. The rabbits were sacrificed 24 h after the procedures, and their echocardiography, stress myocardial contrast echocardiography, pathology, and surgical times were compared. The results demonstrated varying degrees of reduced cardiac function in all three experimental groups, the Open-chest group exhibiting the most significant decline. The myocardial filling in the affected areas was visually analyzed by myocardial contrast echocardiography, revealing sparse filling at rest but more after stress. Quantitative analysis of perfusion parameters (ß, A, MBF) in the affected myocardium showed reduced values, the Open-chest group having the most severe reductions. No differences were observed in stress myocardial acoustic imaging parameters between the Echo-M and Echo-SL groups. Among the pathological presentations, the Open-chest model predominantly exhibited localized ischemia, while the Echo-M model was characterized by mechanical physical embolism, and the Echo-SL model displayed in situ thrombosis as the primary pathological feature. Inflammatory responses and collagen deposition were observed in all groups, with the severity ranking of Open-chest > Echo-SL > Echo-M. The ultrasound-guided intracardiac injection method used in this experiment outperformed open-chest surgery in terms of procedural efficiency, invasiveness, and maneuverability. This study not only optimizes established cardiac injection techniques but also offers valuable evidence to support clinical investigations through a comparison of various modeling methods.

Ultrasound study of right ventricular myocardial perfusion and functional changes in hypertrophic cardiomyopathy.

BACKGROUND: To evaluate the changes of right ventricular (RV) myocardial perfusion and function in patients with hypertrophic cardiomyopathy (HCM) by myocardial contrast echocardiography (MCE) and speckle tracking (2D-STE), and to explore the relationship between RV myocardial perfusion and strain. METHODS: Conventional ultrasound, MCE and 2D-STE were performed on 29 HCM patients and 21 healthy subjects to analyze RV myocardial perfusion, RV global strain, RV free wall strain, and strain of each segment. The correlation between RV myocardial perfusion and strain was further analyzed in HCM patients. RESULTS: MCE results showed that the regional myocardial perfusion of the RV in HCM patients was decreased. Compared with the normal control group, the mean slope (ß) in the middle and apical segments of the RV free wall, and the peak intensity (A), ß, myocardial blood flow (MBF) of the ventricular septum decreased in HCM patients (P < 0.05). RV function was impaired in HCM patients. The RV global strain (RV GLS), and the strain of RV free wall and each segment were lower than those in the normal control group (P < 0.05). Correlation analysis showed that there was a certain correlation between RV myocardial perfusion and strain, such as the ß of the whole RV in HCM group had a positive correlation with the strain of the middle segment of the interventricular septum (r = 0.550, P = 0.002). CONCLUSIONS: The regional myocardial perfusion and strain of the RV in HCM patients are reduced, and there is a positive correlation between them, suggesting that the reduction of myocardial strain may be related to the impairment of myocardial microcirculation.

ECHO provides layer-specific insight of both myocardial deformation and microcirculation dysfunction in dilated cardiomyopathy patients: Clinical value of combined application of left ventricular layer-specific strain and myocardial contrast echocardiography.

AIM: To investigate the pattern of left ventricular (LV) function and myocardial perfusion and their relationship in dilated cardiomyopathy (DCM) patients using layer-specific speckle tracking imaging (STI) and layer-specific myocardial contrast echocardiography (MCE). MATERIAL AND METHODS: Thirty DCM patients and 30 controls were recruited and underwent STI and MCE examination. The peak values of longitudinal strain (LS), circumferential strain (CS) of each layer of LV were recorded and compared between groups. Additionally, cross-sectional area of a microvessel (A) and average myocardial microvascular lesion (ß) of each layer were measured, myocardial blood flow (MBF) was estimated using A × ß, above parameters were compared between two groups. RESULTS: The LS of endo- (LSendo ), mid- (LSmid ) and epicardium (LSepi ), as well as CS of endo- (RSendo ), mid- (RSmid ), (LSepi ) epicardium and LS endo/epi, CS endo/epi were significantly decreased in DCM patients. More importantly, DCM patients demonstrated decreased A, ß and A × ß in all three myocardium layers and A endo/epi, ß endo/epi, A × ß endo/epi compared to the controls. The time to peak and the cardiac cycle required to reach the peak were prolonged in DCM patients (p < 0.05). Longitudinal strain parameters of each layer had a negative relationship with perfusion parameter A and this relationship was strongest between LSendo and Aendo (r = 0.690, p < 0.01). CONCLUSIONS: The cardiac strain and, more importantly, coronary microcirculation perfusion was impaired in each layer in DCM patients. The longitudinal function of the LV myocardium was closely related to changes in myocardial microcirculation perfusion.

Differences in the microcirculation disturbance in the right and left ventricles of neonatal rats with hypoxic pulmonary hypertension.

Microcirculation disturbance is a crucial pathological basis of heart damage; however, microcirculation alterations induced by hypoxic pulmonary hypertension (HPH) remain unknown, and the left ventricle (LV) in HPH is conventionally ignored. Herein, we investigated the changes in the cardiac structure, function and microcirculation after HPH and further compared the differences between the right ventricle (RV) and LV. Using a neonatal rat model of HPH, we found RV myocardial hypertrophy, dysfunction and poor myocardial perfusion in HPH rats. Additionally, RV microcirculation disturbance manifested as the abnormal expression of endothelin-1/eNOS and increased expression of intercellular cell adhesion molecule-1 (ICAM-1) or E-selectin 3 days after hypoxia, followed by vascular inflammation, coronary arterial remodeling and microvascular sparseness. Impairment in LV vasodilation was detected in rats after 3 days of hypoxia; however, no obvious microvascular rarefaction or inflammatory reaction was observed in the LV. In conclusion, our results suggest that HPH mainly triggers RV microcirculation disturbances, causing low myocardial perfusion damage and cardiac dysfunction. Despite the differences in the RV and LV, their impaired microvascular function, mediated by endothelial cells, occurs almost simultaneously after HPH, earlier than cardiac functional or structural abnormalities.

Relationship Between Myocardial Perfusion and Myocardial Function in Dilated Cardiomyopathy by Shown Ultrasonography.

Myocardial contrast echocardiography (MCE) and two-dimensional speckle tracking echocardiography (2D-STE) were used to detect left ventricular myocardial microcirculation perfusion and myocardial systolic function in dilated cardiomyopathy (DCM) and to explore the relationship between the two.Conventional ultrasound, MCE, and 2D-STE examinations were performed on 30 patients and 30 controls. Left ventricular microcirculation perfusion, left ventricular longitudinal strain (GLS), and circumferential strain (GCS) were analyzed to further compare the correlation between left ventricular perfusion and myocardial strain parameters.Regional myocardial perfusion was reduced in patients with DCM, manifesting as a decrease in the rising slope (A) of the mid-segment of the posterior septum, the peak intensity (PI) of the mid-segment of the anterior septum and the posterior septum, the apical segment of the lateral wall, the area under the curve (AUC) of the posterior septum, the basal segment of the posterior wall, the anterior septum, posterior septum, posterior wall, mid-segment of the lateral wall, and apical segment of the lateral wall and the overall average PI and AUC of the mid-segment, compared with that in the controls (P < 0.05). The left ventricular systolic function and the strain parameters GLS and GCS of DCM patients were lower than those of the controls (P < 0.001). Correlation analysis revealed a positive correlation between the A of the mitral valve and GCS (r = 0.372, P = 0.043), and MV-E/e' had a positive correlation with the AUC of the basal and intermediate segments (r = 0.379, P = 0.039; r = 0.404, P = 0.027).In patients with DCM, regional myocardial microcirculation perfusion is reduced, and myocardial strain is impaired. Myocardial perfusion has a good positive correlation with myocardial mechanics.

A New Potential Predictor of Coronary Artery Disease: The Ratio of Mitral Peak Filling Velocity to Mitral Annular Velocity in Early Diastole.

BACKGROUND The aim of this study was to explore the value of the ratio of mitral peak filling velocity (E) to mitral annular velocity (e') in early diastole as a predictor of coronary artery disease (CAD). MATERIAL AND METHODS The study population consisted of 83 consecutive patients (aged 38-77 years, 22 women and 61 men) who received coronary angiography. The E/e' ratio was estimated by echocardiographic examination. Statistical significance was determined by receiver operating characteristic (ROC) curve and multiple logistic regression analyses. RESULTS ROC curve analysis showed that the optimal E/e' ratio cut-off for predicting CAD was 8.153 with a specificity of 72.4% and sensitivity of 57.4%. The area under the ROC curve was 0.635 with a 95% confidence interval (CI) for normal distribution of 0.515-0.755 (p=0.043). Multivariate logistic regression analysis demonstrated that the E/e' ratio was closely associated with CAD (odds ratio [OR], 1.350; 95% CI, 1.087-1.676, p=0.007). CONCLUSIONS The E/e' ratio is a simple and practical predictor of CAD and may be an independent risk factor for CAD. Large-cohort and multi-center studies are required to confirm these observations.

Prognostic Value of Real Time Myocardial Contrast Echocardiography after Percutaneous Coronary Intervention.

Real time myocardial contrast echocardiography (RTMCE) is a cost-effective and simple method to quantify coronary flow reserve (CFR). We aimed to determine the value of RTMCE to predict cardiac events after percutaneous coronary intervention (PCI). We have studied myocardial blood volume (A), velocity (ß), flow indexes (MBF, A × ß), and vasodilator reserve (stress-to-rest ratios) in 36 patients with acute coronary syndrome (ACS) who underwent PCI. CFR (MBF at stress/MBF at rest) was calculated for each patient. Perfusion scores were used for visual interpretation by MCE and correlation with TIMI flow grade. In qualitative RTMCE assessment, post-PCI visual perfusion scores were higher than pre-PCI (Z = -7.26, P < 0.01). Among 271 arteries with TIMI flow grade 3 post-PCI, 72 (36%) did not reach visual perfusion score 1. The ß- and A × ß-reserve of the abnormal segments supplied by obstructed arteries increased after PCI comparing to pre-PCI values (P < 0.01). Patients with adverse cardiac events had significantly lower ß- and lower A × ß-reserve than patients without adverse cardiac events. In the former group, the CFR was ≥ 1.5 both pre- and post-PCI. CFR estimation by RTMCE can quantify myocardial perfusion in patients with ACS who underwent PCI. The parameters ß-reserve and CFR combined might predict cardiac events on the follow-up.

Association of hypercholesterolemia and cardiac function evaluated by speckle tracking echocardiography in a rabbit model.

BACKGROUND: Although hypercholesterolemia is a major risk factor for coronary artery disease (CAD), only limited data are available regarding its direct effect on myocardial function apart from CAD. The aim of this study was to evaluate LV systolic function using speckle-tracking echocardiography and investigate the relationship between hypercholesterolemia and myocardial function. METHODS: Twenty-eight rabbits were randomly divided into three groups: 8 were fed normal chow for 3 months (group 1) and the remaining 20 were fed an atherogenic diet for 2 (group 2) or 3 months (group 3). Global systolic radial, circumferential and longitudinal peak strain were calculated. Serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and myocardial cholesterol levels were measured. RESULTS: Global systolic longitudinal strain were both decreased in the group 2 and 3 (P < 0.001), whereas radial strain were increased (P < 0.001) compared with group 1. Global circumferential strain in the group 3 was significantly reduced (P < 0.001). Serum and myocardial cholesterol concentration markedly increased in the group 2 and group 3 (P < 0.001). There was a significant inverse correlation between longitudinal strain and serum TC, LDL-C as well as myocardial cholesterol levels (r = - 0.723, r = - 0.794, r = - 0.700, P both < 0.001). A significant negative correlation was also noted between circumferential strain and serum TC, LDL-C as well as myocardial cholesterol levels (r = - 0.518, P = 0.007; r = - 0.691, P < 0.001; r = - 0.659, P < 0.001). A significant positive correlation was found between radial strain and serum TC, LDL-C as well as myocardial cholesterol levels (r = 0.432, P = 0.028; r = 0.602, P = 0.001; r = 0.469, P = 0.016). CONCLUSION: Although LV morphology and ejection fractions were not different among the three groups, elevated concentration of cholesterol, especially in serum LDL-C, was significantly associated with LV systolic dysfunction. The findings also indicate that reductions in longitudinal was the first appeared, followed by circumferential, and was compensated for by increasing radial strain.

The impact of segmental volumetric changes on functional mitral regurgitation: a study using three-dimensional regional time-volume analysis combined with low-dose dobutamine.

PURPOSE: Using transthoracic three-dimensional (3D) echo regional volume analysis combined with low-dose dobutamine to investigate the effects on regional volume, mitral configuration and functional mitral regurgitation (FMR). METHODS: Fifty-six patients with ischemic cardiomyopathy (ICM) were included in this study. The effective regurgitant orifice area (EROA) of FMR secondary to ICM with depressed left ventricular ejection fraction was compared with mitral tenting area and coaptation height (CH) before and after low-dose dobutamine (10 µg/kg per min). Using 3-DQ software we measured and calculated regional stroke-volumes (rSV), the ratio of the rSV to the whole left ventricular stroke volume (rgSVratio) in all 17 segments and the average rgSVratio of 4 anterior-PM attached segments (rgSVratio-aver anter-PM), 4 posterior-PM attached segments (rgSVratio-aver post-PM), 8 PMs attached segments (rgSVratio-aver PMs) and all 17 segments before and after dobutamine. RESULTS: Compared with the resting condition, the SVr and rgSVratio on the basal and mid segments of anterior, lateral, inferior, and posterior walls were increased after dobutamine infusion (P < 0.05). EROA at rest was associated with tenting area, CH and rgSVratio-aver of PMs and the reduction in EROA caused by dobutamine was associated with reductions in tenting area, CH and increases in rgSVratio-aver of PMs. Tenting area was associated with rgSVratio-aver of PMs and reduction caused by dobutamine was associated with increases in rgSVratio-aver of PMs. CONCLUSIONS: The FMR decreasing during low-dose dobutamine is quantitatively associated with the regional LV volume change of attached PMs. Real time transthoracic three-dimensional echocardiography may provide a simple and noninvasive approach to assess regional LV time-volume characteristic during FMR.

Combination of 2- and 3-dimensional contrast-enhanced transvaginal sonography for diagnosis of small adnexal masses.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of the combination of 2-dimensional (2D) and 3-dimensional (3D) contrast-enhanced sonography in discriminating between benign and malignant small adnexal masses. METHODS: Selected patients were evaluated with both 2D and 3D contrast-enhanced sonography after conventional sonography before undergoing any surgery. Time-intensity curves for 2D contrast-enhanced sonography were constructed by using contrast-enhanced sonographic software. A vascular perfusion characteristic analysis was achieved by 2D and 3D contrast-enhanced sonography. Results were finally verified by surgery. RESULTS: Forty-seven cases of benign and 10 cases of malignant small adnexal masses were discovered. Significant differences in perfusion patterns, time-intensity curve shapes for 2D contrast-enhanced sonography, grayscale contrast-enhanced sonography, and blood flow imaging on 3D contrast-enhanced sonography were observed between benign and malignant masses (P< .05). Two-dimensional contrast-enhanced sonography, 3D contrast-enhanced sonography, parallel combination of 2D and 3D contrast-enhanced sonography, and serial combination of 2D and 3D contrast-enhanced sonography all reached diagnostic sensitivity of 100% for discriminating benign from malignant masses, whereas specificity values were 61.7%, 63.8%, 68.1%, and 57.4%, respectively. Areas under the receiver operating characteristic curves were 0.809, 0.819, 0.840, and 0.787. CONCLUSIONS: Two-dimensional contrast-enhanced sonography is of high value in distinguishing malignant from benign small adnexal masses; 3D contrast-enhanced sonography provides richer and more useful information for evaluation of these masses. Diagnostic sensitivity of 100% can be achieved when using a serial combination of 2D and 3D contrast-enhanced sonography, although specificity needs further improvement.

Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study.

BACKGROUND: Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. METHODS: A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, ß stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson's correlation, multiple linear regression, and analyses of covariance. RESULTS: All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The ß stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 µm/year in women and 5.8 µm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. CONCLUSIONS: The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography.

Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

The value of aneurysm volume and myocardial strain rate for evaluating cardiac function of ischemia-related left ventricular aneurysm in a rabbit model using real time three-dimensional echocardiographic imaging combined with speckle tracking imaging.

PURPOSE: The aim of this study was to evaluate the effect of left ventricular aneurysm (LVA) volume and myocardial strain on left ventricular function in a rabbit model using real time three-dimensional echocardiographic imaging (RT-3DE) combined with two-dimensional speckle tracking imaging (2D-STI). METHODS: A rabbit model of LVA was prepared in 30 New Zealand rabbits by ligating the middle segment of the left anterior descending artery and the left circumflex artery (LVA group); 10 control rabbits underwent thoracotomy alone. Four weeks later, RT-3DE was performed to obtain data on left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and LVA volume. The peak short-axis radial (SrR) and circumferential (SrC) strain rates were measured using 2D-STI technique. RESULTS: Compared with control rabbits, LVA group rabbits had significant left ventricular enlargement at the end-systolic and end-diastolic phases (both P < 0.05). LVEF, SrR-Systolic, and SrC-Systolic were significantly lower in the LVA group (all P < 0.05). Moreover, there were high correlations between LVEF and SrC-Systolic anterior wall, SrR-Systolic anterior wall, SrC-Systolic lateral wall, and SrR-Systolic lateral wall (r = -0.895, -0.887, -0.890, -0.891, respectively, all P < 0.05). Of note, LVA volume/LVEDV had the tightest inverse relationship with LVEF (r = -0.911, P < 0.01). Specifically, LVA volume/LVEDV >16% corresponded to LVEF <50%, and LVEF decreased 1.1% while LVA volume/LVEDV increased 1%. CONCLUSIONS: LVA volume/LVEDV provided a sensitive indicator reflecting cardiac function with LVA. Measurement of various parameters using RT-3DE might be a useful means to evaluate cardiac function after LVA formation.

Optimization of the cotransfection of SERCA2a and Cx43 genes for myocardial infarction complications.

As our previous study showed, the therapeutic effect of two genes (SERCA2a and Cx43) on heart failure after myocardial infarction (MI) was greater than that of single gene (SERCA2a or Cx43) therapy for bone marrow stem cell (BMSC) transplantation. Based on previous research, the aim of this study was to investigate the optimal ratio of codelivery of SERCA2a and Cx43 genes for MI therapy after biotinylated microbubble (BMB) transplantation via ultrasonic-targeted microbubble destruction (UTMD). Forty rats underwent left anterior descending (LAD) ligation and BMSC injection into the infarct and border zones. Four weeks later, the genes SERCA2a and Cx43 were codelivered at different ratios (1:1, 1:2 and 2:1) into the infarcted heart via UTMD. Cardiac mechanoelectrical function was determined at 4 wks after gene delivery, and the hearts of the rats were harvested for measurement of MI size and detection of SERCA2a and Cx43 expression. Q-PCR analysis of the expression of Nkx2.5 and GATA4 in the myocardial infarct zone and measurement of neovascularization in infarcted hearts. After comparing the therapeutic effects of different cogene ratios, the SERCA2a/Cx43-1:2 group showed remarkable cardiac electrical stability and strengthened the role of anti-arrhythmia. In conclusion, the optimum ratio of the SERCA2a/Cx43 gene is 1:2, which is advantageous for maintaining cardiac electrophysiological stability.

Value of Myocardial Contrast Echocardiography in Detecting Coronary Microcirculatory Dysfunction in Ischemia With Non-obstructive Coronary Artery Disease.

OBJECTIVE: The aim of this study was to evaluate the value of myocardial contrast echocardiography (MCE) in detecting coronary microcirculation function dysfunction in ischemia with non-obstructive coronary artery (INOCA) disease. METHODS: Twenty-one patients with a clinical diagnosis of INOCA were admitted to the First Affiliated Hospital of Xinjiang Medical University because of chest pain. All participants underwent MCE and [18F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography myocardial metabolic imaging. With the results of FDG PET taken as the gold standard, all myocardial segments were divided into a normal control group and a coronary artery microcirculation dysfunction (CMCD) group. We used MCE to measure myocardial perfusion parameters, including the ascending slope (ß), time to peak (TTP), A and A × ß. The receiver operating characteristic (ROC) curves of ß, TTP, A and A × ß were calculated to evaluate the diagnostic value of MCE for CMCD. RESULTS: A total of 122 and 218 segments were investigated in the CMCD and control groups, respectively. On the basis of the statistical analysis of the MCE parameters of the two groups, the myocardial perfusion parameters ß, A and A × ß of all segments in the CMCD group decreased, and the TTP in the basal segment of the CMCD group was longer than that of the normal control group (all p values <0.05). On the basis of analysis of the ROC curve, ß had the highest diagnostic efficiency in the middle segment. CONCLUSION: This study found that MCE is valuable in the diagnosis of non-obstructive coronary artery complicated by CMCD.

Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine.

The present study aimed to screen the best time window for the transplantation of bone marrow mesenchymal stem cells (MSCs) after acute myocardial infarction (MI) through targeted ultrasound microbubbles loaded with SDF-1α antibody. Thirty-six MI miniswine were randomly divided into six experimental groups according to the duration after infarction (1 day, 3 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after infarction). MSCs were labeled with BrdU and then injected through the coronary artery in the stem cell transplantation group to detect the number of transplanted MSCs at different time points after MI. Three miniswine were randomly selected as the control group (sham operation: open chest without ligation of the coronary artery). All SDF-1α groups and control groups were injected with a targeted microbubble ultrasound contrast agent. The values of the myocardial perfusion parameters (A, ß, and A × ß) were determined. A T, ß T, and (A × ß)T varied with time and peaked 1 week after MI (P < 0.05). The number of transplanted stem cells in the myocardium through coronary injection of MSCs at 1 week was the greatest and consistent with the changing tendency of A T, ß T, and (A × ß)T (r = 0.658, 0.778, 0.777, P < 0.05). ß T(X), (A × ß)T(X), and the number of transplanted stem cells was used to establish the regression equation as follows: Y = 36.11 + 17.601X; Y = 50.023 + 3.348X (R 2 = 0.605, 0.604, P < 0.05). The best time window for transplanting stem cells was 1 week after MI. The myocardial perfusion parameters of the SDF-1α targeted contrast agent can be used to predict the number of transplanted stem cells in the myocardial tissue.

Functional evaluation of constructed pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble.

Background: Stem cell transplantation is one of the treatment methods for acute myocardial infarction (AMI). MicroRNA-1 contributes to the study of the essential mechanisms of stem cell transplantation for treating AMI by targeted regulating the myocardial microenvironment after stem cell transplantation at the post-transcriptional level. Thus, microRNA-1 participates in regulating the myocardial microenvironment after stem cell transplantation, a promising strategy for the Stem cell transplantation treatment of AMI. However, the naked microRNA-1 synthesized is extremely unstable and non-targeting, which can be rapidly degraded by circulating RNase. Herein, to safely and effectively targeted transport the naked microRNA-1 synthesized into myocardial tissue, we will construct pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble pAd-AAV-9/miRNA-1 NB and evaluate its characteristics, targeting, and function. Methods: The pAd-AAV-9/miRNA-1 gene complex was linked to nanobubble NBs by the "avidin-biotin bridging" method to prepare cardiomyocyte-targeted nanobubble pAd-AAV-9/miRNA-1 NB. The shape, particle size, dispersion, and stability of nanobubbles and the connection of pAd-AAV-9/miRNA-1 gene complex to nanobubble NB were observed. The virus loading efficiency was determined, and the myocardium-targeting imaging ability was evaluated using contrast-enhanced ultrasound imaging in vivo. The miRNA-1 expression level in myocardial tissue and other vital organs ex vivo of SD rats was considered by Q-PCR. Also, the cytotoxic effects were assessed. Results: The particle size of NBs was 504.02 ± 36.94 nm, and that of pAd-AAV-9/miRNA-1 NB was 568.00 ± 37.39 nm. The particle size and concentration of pAd-AAV-9/miRNA-1 NBs did not change significantly within 1 h at room temperature (p > 0.05). pAd-AAV-9/miRNA-1 NB had the highest viral load rate of 86.3 ± 2.2% (p < 0.05), and the optimum viral load was 5 µL (p < 0.05). pAd-AAV-9/miRNA-1 NB had good contrast-enhanced ultrasound imaging in vivo. Quantitative analysis of miRNA-1 expression levels in vital organs ex vivo of SD rats by Q-PCR showed that pAd-AAV-9/miRNA-1 NB targeted the myocardial tissue. Q-PCR indicated that the expression level of miRNA-1 in the myocardium of the pAd-AAV-9/miRNA-1 NB + UTMD group was significantly higher than that of the pAd-AAV-9/miRNA-1 NB group (p < 0.05). pAd-AAV-9/miRNA-1 NB had no cytotoxic effect on cardiomyocytes (p > 0.05). Conclusion: The pAd-AAV-9/miRNA-1 NB constructed in this study could carry naked miRNA-1 synthesized in vitro for targeted transport into myocardial tissue successfully and had sound contrast-enhanced imaging effects in vivo.

Experimental study on the optimization of ANM33 release in foam cells.

Given the miR-33's mechanistic relationships with multiple etiological factors in the pathogenesis of atherosclerosis (AS), we investigated the therapeutic potentials of dual-targeted microbubbles (HA-PANBs) in foam cell-specific release of anti-miR-33 (ANM33) oligonucleotides, resulting in the early prevention of AS progression and severity. The intracellular localization, loading optimization, and therapeutic effects of HA-PANBs were examined in detail in a co-cultured cell model of phagocytosis. Compared with non-targeting nanobubbles (NBs) and single-targeted microbubbles as controls, HA-PANBs efficiently delivered the ANM33 specifically to foam cells via sustained release, exhibiting its clinical value in mediating RNA silencing. Moreover, when used at a dose of 12 µg/mL HA-PANBs per 107 cells for 48 h, a higher release rate and drug efficacy were observed. Therefore, HA-PANBs, effectively targeting early AS foam cells, may represent a novel and optimal gene therapy approach for AS management.

Dual-modal molecular imaging and therapeutic evaluation of coronary microvascular dysfunction using indocyanine green-doped targeted microbubbles.

Coronary microvascular dysfunction (CMD), which causes a series of cardiovascular diseases, seriously endangers human health. However, precision diagnosis of CMD is still challenging due to the lack of sensitive probes and complementary imaging technologies. Herein, we demonstrate indocyanine green-doped targeted microbubbles (named T-MBs-ICG) as dual-modal probes for highly sensitive near-infrared (NIR) fluorescence imaging and high-resolution ultrasound imaging of CMD in mouse models. In vitro results show that T-MBs-ICG can specifically target fibrin, a specific CMD biomarker, via the cysteine-arginine-glutamate-lysine-alanine (CREKA) peptide modified on the surface of microbubbles. We further employ T-MBs-ICG to achieve NIR fluorescence imaging of injured myocardial tissue in a CMD mouse model, leading to a signal-to-background ratio (SBR) of up to 50, which is 20 fold higher than that of the non-targeted group. Furthermore, ultrasound molecular imaging of T-MBs-ICG is obtained within 60 s after intravenous injection, providing molecular information on ventricular and myocardial structures and fibrin with a resolution of 1.033 mm × 0.466 mm. More importantly, we utilize comprehensive dual-modal imaging of T-MBs-ICG to evaluate the therapeutic efficacy of rosuvastatin, a cardiovascular drug for the clinical treatment of CMD. Overall, the developed T-MBs-ICG probes with good biocompatibility exhibit great potential in the clinical diagnosis of CMD.