Modulating Lysine Crotonylation in Cardiomyocytes Improves Myocardial Outcomes.

BACKGROUND: Ischemic heart disease is a major global public health challenge, and its functional outcomes remain poor. Lysine crotonylation (Kcr) was recently identified as a post-translational histone modification that robustly indicates active promoters. However, the role of Kcr in myocardial injury is unknown. In this study, we aimed to clarify the pathophysiological significance of Kcr in cardiac injury and explore the underlying mechanism. METHODS: We investigated the dynamic change of both the Kcr sites and protein level in left ventricular tissues at 2 time points following sham or cardiac ischemia-reperfusion injury, followed by liquid chromatography-coupled tandem mass tag mass spectrometry. After validation of the enriched protein Kcr by immunoprecipitation and Western blot, the function and mechanism of specific Kcr sites were further investigated in vitro and in vivo by gain- or loss-of-function mutations targeting Kcr sites of selected proteins. RESULTS: We found that cardiac ischemia-reperfusion injury triggers preferential Kcr of proteins required for cardiomyocyte contractility, including mitochondrial and cytoskeleton proteins, which occurs largely independently of protein-level changes in the same proteins. Those exhibiting Kcr changes were associated not only with disruption of cardiomyocyte mitochondrial, sarcomere architecture, and gap junction but also with cardiomyocyte autophagy and apoptosis. Modulating site-specific Kcr of selected mitochondrial protein IDH3a (isocitrate dehydrogenase 3 [NAD+] alpha) at K199 and cytoskeletal protein TPM1 (tropomyosin alpha-1 chain) at K28/29 or enhancing general Kcr via sodium crotonate provision not only protects cardiomyocyte from apoptosis by inhibiting BNIP3 (Bcl-2 adenovirus E18 19-kDa-interacting protein 3)-mediated mitophagy or cytoskeleton structure rearrangement but also preserves postinjury myocardial function by inhibiting fibrosis and apoptosis. CONCLUSIONS: Our results indicate that Kcr modulation is a key response of cardiomyocytes to ischemia-reperfusion injury and may represent a novel therapeutic target in the context of ischemic heart disease.

Two-dimensional speckle tracking echocardiography demonstrates improved myocardial function after intravenous infusion of bone marrow mesenchymal stem in the X-Linked muscular dystrophy mice.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) are commonly used in regenerative medicine. However, it is not clear whether transplantation of BMSCs can improve cardiac function of the X-Linked Muscular Dystrophy Mice (mdx) and how to detect it. We aimed to investigate the role of speckle tracking echocardiography (STE) in detecting cardiac function of the BMSCs-transplanted mdx in comparison with the untreated mdx. METHODS: The experimental mice were divided into the BMSCs-transplanted mdx, untreated mdx, and control mice groups (n = 6 per group). The BMSCs were transplanted via tail vein injections into a subset of mdx at 20 weeks of age. After four weeks, the cardiac functional parameters of all the mice in the 3 groups were analyzed by echocardiography. Then, all the mice were sacrificed, and the cardiac tissues were harvested and analyzed by immunofluorescence. The serum biochemical parameters were also analyzed to determine the beneficial effects of BMSCs transplantation. RESULTS: Traditional echocardiography parameters did not show statistically significant differences after BMSCs transplantation for the three groups of mice. In comparison with the control group, mdx showed significantly lower left ventricular (LV) STE parameters in both the long-axis and short-axis LV images (P < 0.05). However, BMSCs-transplanted mdx showed improvements in several STE parameters including significant increases in a few STE parameters (P < 0.05). Immunofluorescence staining of the myocardium tissues showed statistically significant differences between the mdx and the control mice (P < 0.05), and the mdx transplanted with BMSCs demonstrated significantly improvement compared with the untreated mdx (P < 0.05). CONCLUSION: This study demonstrated that the early reduction in the LV systolic and diastolic function in the mdx were accurately detected by STE. Furthermore, our study demonstrated that the transplantation of BMSCs significantly improved myocardial function in the mdx.

Prenatal Diagnosis of Fetal Oral Masses by Ultrasound Combined With Magnetic Resonance Imaging.

OBJECTIVES: To analyze the imaging manifestations of common fetal oral masses by ultrasound combined with magnetic resonance imaging (MRI) and to discuss their differential diagnoses. METHODS: A retrospective study of 6 fetuses with oral masses was performed at a tertiary referral center. The imaging features of prenatal ultrasonography and MRI in the diagnosis of fetal oral masses were analyzed. RESULTS: Histopathological examination and/or postpartum ultrasound revealed lymphangioma malformation in 2 fetuses, and mucosal retention cyst, mature teratoma, immature teratoma, and cranial meningocele in 1 fetus, respectively. The teratoma had a characteristic sonographic appearance. In our study, the 4 cases of cystic masses did not have an abnormal vessel architecture. Supplemental MRI revealed a mass effect at the level of the hypopharynx, and in 2 cases with polyhydramnios, the mass obstructed the fetuses' upper airway. Thus, ex-utero intrapartum therapy surgery was performed to secure the newborn's airway. CONCLUSIONS: Oral fetal tumors represent rare congenital malformations. This study shows that a prenatal diagnosis of oral masses is feasible by ultrasound examination. MRI can further confirm the results of ultrasonography and clearly show the relationship between the mass and the hypopharynx. Ultrasonography combined with MRI could, to a large extent, facilitate early detection and appropriate treatment and improve outcome.

Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib.

The third-generation tyrosine kinase inhibitor (TKI) ponatinib has been associated with high rates of acute ischemic events. The pathophysiology responsible for these events is unknown. We hypothesized that ponatinib produces an endothelial angiopathy involving excessive endothelial-associated von Willebrand factor (VWF) and secondary platelet adhesion. In wild-type mice and ApoE-/- mice on a Western diet, ultrasound molecular imaging of the thoracic aorta for VWF A1-domain and glycoprotein-Ibα was performed to quantify endothelial-associated VWF and platelet adhesion. After treatment of wild-type mice for 7 days, aortic molecular signal for endothelial-associated VWF and platelet adhesion were five- to sixfold higher in ponatinib vs sham therapy (P < .001), whereas dasatinib had no effect. In ApoE-/- mice, aortic VWF and platelet signals were two- to fourfold higher for ponatinib-treated compared with sham-treated mice (P < .05) and were significantly higher than in treated wild-type mice (P < .05). Platelet and VWF signals in ponatinib-treated mice were significantly reduced by N-acetylcysteine and completely eliminated by recombinant ADAMTS13. Ponatinib produced segmental left ventricular wall motion abnormalities in 33% of wild-type and 45% of ApoE-/- mice and corresponding patchy perfusion defects, yet coronary arteries were normal on angiography. Instead, a global microvascular angiopathy was detected by immunohistochemistry and by intravital microscopy observation of platelet aggregates and nets associated with endothelial cells and leukocytes. Our findings reveal a new form of vascular toxicity for the TKI ponatinib that involves VWF-mediated platelet adhesion and a secondary microvascular angiopathy that produces ischemic wall motion abnormalities. These processes can be mitigated by interventions known to reduce VWF multimer size.

High-intensity focused ultrasound ablation of myocardium in vivo and instantaneous biological response.

OBJECTIVE: This study aimed to evaluate the instantaneous biological response of canine myocardium in vivo to high-intensity focused ultrasound (HIFU) ablation, and thereby determine the feasibility of this method. METHODS: Left ventricle myocardium HIFU ablation was performed on six dogs at four levels of HIFU energy (acoustic intensity was 3000 W/cm2 ; ablation durations were 1.2, 2.4, 3.6, and 4.8 sec, respectively). Gross lesion volumes were confirmed and assessed by tetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and electron microscopy. Global cardiac function and focal wall motion were evaluated by echocardiography. Blood enzymes and cardiac troponin T (CTnT) were tested after ablation. HIFU ablation was repeated on another set of six fresh canine hearts in vitro at the same four energy levels. Focal maximum temperatures were detected both in vivo and in vitro. RESULTS: Different sizes of ablation via HIFU can be created in beating hearts using controlled energy emission. Focal maximum temperatures varied from 62 ± 4.8 °C to 81 ± 12.9 °C. The lesion sizes were significantly smaller in vivo than in vitro, as verified by TTC and HE staining. Focal wall motion immediately decreased after ablation (P < 0.05), although the ejection fraction (EF) and E/A ratio were unchanged (P > 0.05). Enzymes and CTnT immediately increased. CONCLUSION: HIFU can be used for the controllable ablation of myocardial tissue, with instantly increased serum markers, decreased regional wall motion, and unaffected left ventricular global function.

Clinical value of quantitative analysis of contrast-enhanced ultrasonography in the differential diagnosis of benign and malignant pelvic tumors.

Background: Cervical cancer, endometrial cancer, and ovarian cancer are among the top 10 most common cancers in women, with ovarian cancer in particular being considered a "silent killer". Therefore, early detection, diagnosis, and treatment constitute important means of care for women's health. This study investigated the clinical value of the quantitative analysis of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign and malignant pelvic tumors. Methods: CEUS was performed on 151 patients with pelvic masses. Subsequently, a qualitative diagnosis was completed using the image enhancement features and tumor parameters. A multiparametric analysis of CEUS images was performed, which included the following parameters: arrival time (AT), time to peak (TTP), peak intensity (PI), and ascent slope (AS). In addition, the qualitative diagnostic efficiency of CEUS was assessed in a multiparametric analysis, and the results were compared with pathological findings. Results: The patients in the malignant group were older (P=0.001) and had larger lesion PI values (P<0.01) than those in the benign group. The PI difference (PId) and the AS difference (ASd) showed statistical differences (P<0.01) between the myometrium and lesion tissues in the same patient. Moreover, the PId and ASd showed the largest receiver operating characteristic (ROC) curve and area under the ROC curve (AUC), with sensitivities of 90.9% and 91.7% and specificities of 86.4% and 72.5%, respectively. Conclusions: The quantitative analysis of CEUS provides a new, simpler, and more accurate method for the differential diagnosis of benign and malignant pelvic masses in clinical practice. The sensitivities and specificities of PId and ASd were higher compared to other parameters from the same patient.

Primary gastric cancer presenting with a metastatic embolus in the common carotid artery: a case report.

Although about 30% of gastric cancers have distant metastasis at the time of initial diagnosis, metastatic tumor embolus in the main blood vessels is not common, especially in the main artery. The report presents, for the first time, an extremely rare clinical case of a metastatic embolus in the common carotid artery (CCA) from primary gastric cancer. Metastatic embolus from the primary tumor should be considered when patients present with gastric cancer accompanied by intravascular emboli. The patient should be actively examined further so as to allow early detection and treatment.

Contrast-enhanced ultrasonography for differential diagnosis of adnexal masses.

Background: Quantitative contrast-enhanced ultrasonography parameters are affected by various factors. We evaluated corrected quantitative contrast enhanced ultrasonography in differentiating benign adnexal tumors from malignant tumors. Methods: Patients with adnexal masses who underwent conventional and contrast-enhanced ultrasonography were included. Contrast-enhanced ultrasonography parameters such as base intensity, arrival time, peak intensity, time to peak intensity, ascending slope, and descending slope were measured. Corrected (time to peak intensity - arrival time) mass/(time to peak intensity - arrival time) uterus and (peak intensity - base intensity) mass/(peak intensity - base intensity) uterus were calculated. Lesions were confirmed by pathologic examination of surgical specimens. Results: This study included 31 patients with 35 adnexal lesions including 20 (57.10%) benign and 15 (42.90%) malignant lesions. The corrected contrast-enhanced ultrasonography quantitative parameters in lesions were statistically different between malignant and benign groups (P<0.05). The optimal cut-off value for (time to peak intensity - arrival time) mass/(time to peak intensity - arrival time) uterus, ascending slope, and (peak intensity - base intensity) mass/(peak intensity - base intensity) uterus, and descending slope for differentiating malignant adnexal masses from benign tumors were 1.05 (area under curve: 0.93, P<0.05), 1.11 (area under curve: 0.83, P<0.05), 0.82 (area under curve: 0.73, P<0.05), and -0.27 (area under curve: 0.66, P=0.16), with sensitivity and specificity of 93.33% and 85.00%, 86.67% and 75.00%, 86.67% and 60.00%, and 54.55% and 66.67%, respectively. Conclusions: Corrected contrast-enhanced ultrasonography parameters provide practical differential diagnosis value of adnexal lesions with high reliability for sonologists.

Echocardiographic findings for improved prenatal diagnosis of aortic coarctation with ventricular septal defect.

Accurate prenatal diagnosis of coarctation of the aorta (CoA) associated with ventricular septal defect (VSD) remains challenging. The objective of the study was to identify which Doppler and/or two-dimensional sonographic findings are most useful for predicting fetal CoA/VSD. A retrospective cohort study identified 35 fetuses with suspected CoA/VSD. Prenatal imaging characteristics included the right ventricular/left ventricular, pulmonary artery (PA)/aorta ratio, aortic isthmus (AOI) Z score, diastolic velocity-time integral (VTID), and systolic velocity-time integral (VTIS) at the AOI. The area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were calculated. Significant differences in the PA/AO, VTID, VTID/VTIS, VTID/VTIS, VTID/(VTID + VTIS), and AOI Z score between the true CoA group and false positives were found. When associated with VSD, the VTID/VTIS and VTID/(VTID + VTIS) had the highest AUC (0.97, 95% confidence interval: 0.84-1.00), with 88.46% sensitivity and 100.00% specificity for predicting the true CoA. The AOI Z score had the highest sensitivity (92.31%). Adding the VTID/VTIS to the AOI Z score significantly improved the performance (IDI, 50%; NRI, 82%; P < 0.05), with an improvement in specificity (77.78% vs. 55.56%; non-Event P = 0.008) without sacrificing sensitivity (96.15% vs. 92.31%; Event P = 0.564). In fetuses with suspected CoA associated with VSD, the quantitative spectral Doppler metric aided accurate detection of the fetal CoA, with reduced false positives. The conventional AOI Z score plus spectral Doppler metric may improve the overall diagnostic accuracy of CoA/VSD.

Non-Invasive Detection of Fetal Vascular Endothelial Function in Gestational Diabetes Mellitus.

Objectives: Endothelial dysfunction in the fetuses of women with gestational diabetes mellitus (GDM) is associated with their subsequent cardiovascular events. Prenatal assessment of endothelial function in fetuses exposed to intrauterine hyperglycemic environment remains challenging. The aim of this study was to assess the fetal vascular endothelial function in GDM patients using color M-mode derived aortic propagation velocity (APV) and evaluate the correlation of APV with endothelial function biomarkers. Methods: This observational cross-sectional study included 31 gestational diabetic mothers and 30 healthy pregnant mothers from August 2019 to January 2020. Clinical data were compared between the groups. Fetal APV was measured using color M-mode echocardiography at late gestation. Concentrations of endothelial biomarkers including von Willebrand Factor (vWF), vascular endothelial-cadherin and endothelin-1 in umbilical cord serum were assessed. Measurements between diabetic group and controls were compared. Results: vWF was the only endothelial functional marker that differed between the two groups. Fetuses in the GDM group had significantly lower APV levels and higher vWF levels compared with the healthy controls (P < 0.05). There was a moderate but significant correlation between APV and vWF (r =-0.58, P < 0.001). There were no associations between APV and ventricular wall thickness or umbilical artery pulsatility index. Conclusions: Color M-mode propagation velocity of aorta is a non-invasive, practical method that correlates well with GDM and fetal endothelial function. This novel metric could contribute to recognizing early vascular functional alterations and hence represents a potential strategy for early risk factor surveillance and risk modification.

Echocardiographic Molecular Imaging of the Effect of Anticytokine Therapy for Atherosclerosis.

BACKGROUND: Echocardiographic molecular imaging techniques are beginning to be applied to evaluate preclinical efficacy of new drugs. In a large clinical trial, anti-interleukin-1ß (IL-1ß) immunotherapy reduced atherosclerotic events, yet treatment effects were modest, and the mechanisms of action were not fully elucidated. We tested the hypothesis that echocardiographic molecular imaging can assess changes in vascular thromboinflammatory status in response to anti-IL-1ß therapy. METHODS: In wild-type and atherosclerotic mice deficient for the low-density lipoprotein-receptor and Apobec-1, closed-chest myocardial infarction (MI) was performed to mimic high-risk clinical cohorts. Control animals had sham surgery. Post-MI animals were randomized to either no therapy or anti-IL-1ß immunotherapy, which was continued weekly. At post-MI day 3 or 21, in vivo ultrasound molecular imaging of aortic VCAM-1, P-selectin, von Willebrand factor A1-domain, and platelet GPIbα in the thoracic aorta was performed. Aortic histology and NF-κB activity were assessed in atherosclerotic mice. RESULTS: In both atherosclerotic and wild-type mice, MI produced a several-fold increase (P < .05) in aortic molecular signals for P-selectin, VCAM-1, von Willebrand factor, and GPIbα. In atherosclerotic mice, signal remained elevated at day 21. Anti-IL-1ß therapy completely abolished the post-MI increase in signal for all endothelial targets (P < .05 vs nontreated) at day 3 and 21. In atherosclerotic mice, MI triggered an increase in aortic plaque growth and macrophage content, a decrease in plaque collagen, and elevated aortic NF-κB (P < .05 for all changes). All of these remote plaque adverse changes were inhibited by anti-IL-1ß therapy. CONCLUSIONS: Echocardiographic molecular imaging of the vascular endothelium can quantify the beneficial effects of therapies designed to suppress the proatherosclerotic arterial thromboinflammatory effects of alarmins such as IL-1ß. This approach could potentially be used to evaluate the biologic variables that influence response in preclinical studies, and possibly to select patients most likely to benefit from therapy.

Assessment of interventricular dyssynchrony by real time three-dimensional echocardiography: an in vitro study in a porcine model.

BACKGROUND: Loss of synchronous contraction between or within the right and left ventricle (RV, LV) leads to adverse ventricular function. We used real time three-dimensional echocardiography (RT3DE) for evaluation of severity of interventricular dyssynchrony and function in a porcine heart model. METHODS: Six fresh in vitro porcine hearts were used to create a controlled model of LV and RV dyssynchrony using two sets of pulsatile pumps. Synchronized and dyssynchronized pump settings were used with two different dyssynchronized settings: LV filled first and RV filled first. RESULTS: There was good correlation between actual measurement and RT3DE for interventricular time difference (r = 0.95, P < 0.0001) and stroke volume (SV) for LV and RV (0.89, 0.85; P < 0.0001, respectively). RT3DE data showed a small but significant underestimation for actual volume (P < 0.05). The intra- and interobserver variabilities are 2.9 +/- 1.5% and 3.1 +/- 5.4% for LV and RV SVs, and 1.7 +/- 2.4% and 2.2 +/- 3.2% for time differences by RT3DE. There was significant difference in RV SV between synchrony and dyssynchrony when the RV filled first (P < 0.05), but not in other groups. The same pattern was found in RT3DE derived SVs (synchrony versus dyssynchrony with RV filled first, P < 0.05). CONCLUSIONS: There is no compromise in LV SV during interventricular dyssynchrony; but RV SV was significantly diminished when the RV filled first. RT3DE is a feasible, robust and reproducible method to identify interventricular dyssynchrony and to evaluate ventricular SVs.

Evaluation of atrial septal defect using real-time three-dimensional echocardiography: comparison with surgical findings.

The present study evaluated the application of three dimensional echocardigraphy (3DE) in the diagnosis of atrial septal defect (ASD) and the measurement of its size by 3DE and compared the size with surgical findings. Two-dimensional and real-time three dimensional echocardiography (RT3DE) was performed in 26 patients with atrial septal defect, and the echocardiographic data were compared with the surgical findings. Significant correlation was found between defect diameter by RT3DE and that measured during surgery (r=0.77, P<0.001). The defect area changed significantly during cardiac cycle. Percentage change in defect size during cardiac cycle ranged from 6%-70%. Our study showed that the size and morphology of atrial septal defect obtained with RT3DE correlate well with surgical findings. Therefore, RT3DE is a feasible and accurate non-invasive imaging tool for assessment of atrial septal size and dynamic changes.

Evaluation of the left ventricular remodeling in patients with myocardial infarction after revascularization with intravenous real-time myocardial contrast echocardiography.

In order to evaluate the left ventricular remodeling in patients with myocardial infarction after revascularization with intravenous real-time myocardial contrast echocardiography (RT-MCE), intravenous RT-MCE was performed on 20 patients with myocardial infarction before coronary revascularization. Follow-up echocardiography was performed 3 months after coronary revascularization. Segmental wall motion was assessed using 18-segment LV model and classified as normal, hypokinesis, akinesis and dyskinesis. Myocardial perfusion was assessed by visual interpretation and divided into 3 conditions: homogeneous opacification=1; partial or reduced opacification or subendocardial contrast defect=2; contrast defect=3. Myocardial perfusion score index (MPSI) was calculated by dividing the total sum of contrast score by the total number of segments with abnormal wall motion. Twenty patients were classified into 2 groups according to the MPSI: MPSI1.5 as poor myocardial perfusion. To assess the left ventricular remodeling, the following comparisons were carried out: (1) Comparisons of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) before and 3 months after revascularization in two groups; (2) Comparisons of LVEF, LVESV and LVEDV pre-revascularization between two groups and comparisons of these 3 months post-revascularization between two groups; (3) Comparisons of the differences in LVEF, LVESV and LVEDV between 3 months post-and pre-revascularization (DeltaLVEF, DeltaLVESV and DeltaLVEDV) between two groups; (4) The linear regression analysis between DeltaLVEF, DeltaLVESV, DeltaLVEDV and MPSI. The results showed that the LVEF obtained 3 months after revascularization in patients with MPSI>1.5 was obviously lower than that in those with MPSI1.5 was obviously larger than that in those with MPSI1.5 and those with MPSI

Evaluation of carotid atherosclerotic plaque stability with contrast-enhanced ultrasonography.

This study was aimed to evaluate the relationship between carotid atherosclerotic plaque stability and the clinical symptoms in patients with carotid atherosclerotic plaques by using contrast-enhanced ultrasonography. Fifty patients with carotid atherosclerotic plaques were enrolled and examined with contrast-enhanced ultrasonography. The correlation of contrast agent enhancement of the carotid atherosclerotic plaques and the clinical symptoms was analyzed. The results showed that among the 50 patients, plaques were enhanced in the 23 patients with obvious clinical symptoms. In 27 patients without apparent clinical symptoms, plaques were enhanced sparsely in 15 patients and not enhanced in 12 patients. It was suggested that contrast-enhanced ultrasonography could be used for the examination of the microcirculation in carotid atherosclerotic plaques on real-time basis and serve as a new noninvasive approach for the assessment of stability of carotid atherosclerotic plaques.

Value of quantitative tissue velocity imaging in the detection of regional myocardial function in dogs with acute subendocardial ischemia.

This study evaluated the application of quantitative tissue velocity imaging (QTVI) in assessing regional myocardial systolic and diastolic functions in dogs with acute subendocardial ischemia. Animal models of subendocardial ischemia were established by injecting microspheres (about 300 microm in diameter) into the proximal end of left circumflex coronary artery in 11 hybrid dogs through cannulation. Before and after embolization, two-dimensional echocardiography, QTVI and real-time myocardial contrast echocardiography (RT-MCE) via intravenous infusion of self-made microbubbles, were performed, respectively. The systolic segmental wall thickening and subendocardial myocardial longitudinal velocities of risk segments before and after embolization were compared by using paired t analysis. The regional myocardial video intensity versus contrast time could be fitted to an exponential function: y=A.(1-exp(-beta.t)), in which the product of A and beta provides a measure of myocardial blood flow. RT-MCE showed that subendocardial normalized A.beta was decreased markedly from 0.99+/-0.19 to 0.35+/-0.11 (P<0.05) in 28 left ventricular (LV) myocardial segments after embolization, including 6 basal and 9 middle segments of lateral wall (LW), 8 middle segments of posterior wall (PW) and 5 middle segments of inferior wall (IW). However, there was no statistically significant difference in subepicardial layer before and after embolization. Accordingly, the ratio of A.beta of subendocardial myocardium to subepicardial myocardium in these segments was significantly decreased from 1.10+/-0.10 to 0.31+/-0.07 (P<0.05). Although the systolic wall thickening did not change 5 min after the embolization in these ischemic segments (29%+/-3% vs 31%+/-5%, P>0.05), the longitudinal peak systolic velocities (Vs) and early-diastolic peak velocities (Ve) recorded by QTVI were declined significantly (P<0.05). Moreover, the subendocardial velocity curves during isovolumic relaxation predominantly showed positive waves, whereas they mainly showed negative waves before the embolization. This study demonstrates that QTVI can more sensitively and accurately detect abnormal regional myocardial function and post-systolic systole caused by acute subendocardial ischemia.

Evaluation of myocardial viability after myocardial infarction with intravenous real-time myocardial contrast echocardiography.

The myocardial viability after myocardial infarction was evaluated by intravenous myocardial contrast echocardiography. Intravenous real-time myocardial contrast echocardiography was performed on 18 patients with myocardial infarction before coronary revascularization. Follow-up echocardiography was performed 3 months after coronary revascularization. Segmental wall motion was assessed using 18-segment LV model and classified as normal, hypokinesis, akinesis and dyskinesis. Viable myocardium was defined by evident improvement of segmental wall motion 3 months after coronary revascularization. Myocardial perfusion was assessed by visual interpretation and divided into 3 conditions: homogeneous opacification; partial or reduced opacification or subendocardial contrast defect; contrast defect. The former two conditions were used as the standard to define the viable myocardium. The results showed that 109 abnormal wall motion segments were detected among 18 patients with myocardial infarction, including 47 segments of hypokinesis, 56 segments of akinesis and 6 segments of dyskinesis. The wall motion of 2 segments with hypokinesis before coronary revascularization which showed homogeneous opacification, 14 of 24 segments with hypokinese and 20 of 24 segments with akinese before coronary revascularization which showed partial or reduced opacification or subendocardial contrast defect was improved 3 months after coronary revascularization. In our study, the sensitivity and specificity of evaluation of myocardial viability after myocardial infarction by intravenous real-time myocardial contrast echocardiography were 94.7% and 78.9%, respectively. It was concluded that intravenous real-time myocardial contrast echocardiography could accurately evaluate myocardial viability after myocardial infarction.

Myocardial Infarction Produces Sustained Proinflammatory Endothelial Activation in Remote Arteries.

BACKGROUND: In the months after acute myocardial infarction (MI), risk for acute atherothrombotic events in nonculprit arteries increases several fold. OBJECTIVES: This study investigated whether sustained proinflammatory and prothrombotic endothelial alterations occur in remote vessels after MI. METHODS: Wild-type mice, atherosclerotic mice with double knockout (DKO) of the low-density lipoprotein receptor and Apobec-1, and DKO mice treated with the Nox-inhibitor apocynin were studied at baseline and at 3 and 21 days after closed-chest MI. Ultrasound molecular imaging of P-selectin, vascular cell adhesion molecule (VCAM)-1, von Willebrand factor (VWF) A1-domain, and platelet GPIbα was performed. Intravital microscopy was used to characterize post-MI leukocyte and platelet recruitment in the remote microcirculation after MI. RESULTS: Aortic molecular imaging for P-selectin, VCAM-1, VWF-A1, and platelets was increased several-fold (p < 0.01) 3 days post-MI for both wild-type and DKO mice. At 21 days, these changes resolved in wild-type mice but persisted in DKO mice. Signal for platelet adhesion was abolished 1 h after administration of ADAMTS13, which regulates VWF multimerization. In DKO and wild-type mice, apocynin significantly attenuated the post-MI increase for molecular targets, and platelet depletion significantly reduced P-selectin and VCAM-1 signal. On intravital microscopy, MI resulted in remote vessel leukocyte adhesion and platelet string or net complexes. On histology, high-risk inflammatory features in aortic plaque increased in DKO mice 21 days post-MI, which were completely prevented by apocynin. CONCLUSIONS: Acute MI stimulates a spectrum of changes in remote vessels, including up-regulation of endothelial inflammatory adhesion molecules and platelet-endothelial adhesion from endothelial-associated VWF multimers. These remote arterial alterations persist longer in the presence of hyperlipidemia, are associated with accelerated plaque growth and inflammation, and are attenuated by Nox inhibition.

Use of cationic microbubbles targeted to P-selectin to improve ultrasound-mediated gene transfection of hVEGF165 to the ischemic myocardium.

Gene therapies have been applied to the treatment of cardiovascular disease, but their use is limited by the need to deliver them to the right target. We have employed targeted contrast ultrasound-mediated gene transfection (TCUMGT) via ultrasound-targeted microbubble destruction (UTMD) to transfer therapeutic genes to specific anatomic and pathological targets. Phospholipid microbubbles (MBs) with pcDNA3.1-human vascular endothelial growth factor 165 (pcDNA3.1-hVEGF165) plasmids targeted to P-selectin (MB+P+VEGFp) were created by conjugating monoclonal antibodies against P-selectin to the lipid shell. These microbubbles were divided into four groups: microbubble only (MB), microbubble+P-selectin (MB+P), microbubble+pcDNA3.1-hVEGF165 plasmid (MB+VEGFp), and microbubble+ P-selectin+pcDNA3.1-hVEGF165 plasmid (MB+P+VEGFp). The reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) results showed that the VEGF gene was successfully transfected by TCUMGT and the efficiency is increased with P-selectin targeting moiety. UTMD-mediated delivery of VEGF increased myocardial vascular density and improved cardiac function, and MB+P+VEGFp delivery showed greater improvement than MB+VEGFp. This study drew support from TCUGMT technology and took advantage of targeted ultrasound contrast agent to identify ischemic myocardium, release pcDNA3.1-hVEGF165 recombinant plasmid, and improve the myocardial microenvironment, so promoting the restoration of myocardial function.