Left Ventricular Anterior Wall Research Articles

Advanced maternal age alters cardiac functional and structural adaptations to pregnancy in rats.

A significant number of pregnancies occur at advanced maternal age (>35 yr), which is a risk factor for pregnancy complications. Healthy pregnancies require massive hemodynamic adaptations, including an increased blood volume and cardiac output. There is growing evidence that these cardiovascular adaptations are impaired with age, however, little is known about maternal cardiac function with advanced age. We hypothesized that cardiac adaptations to pregnancy are impaired with advanced maternal age. Younger (4 mo; ∼early reproductive maturity in humans) and aged (9 mo; ∼35 yr in humans) pregnant Sprague-Dawley rats were assessed and compared with age-matched nonpregnant controls. Two-dimensional echocardiographic images were obtained (ultrasound biomicroscopy; under anesthesia) on gestational day 19 (term = 22 days) and compared with age-matched nonpregnant rats (n = 7-9/group). Left ventricular structure and function were assessed using short-axis images and transmitral Doppler signals. During systole, left ventricular anterior wall thickness increased with age in the nonpregnant rats, but there was no age-related difference between the pregnant groups. There were no significant pregnancy-associated differences in left ventricular wall thickness. Calculated left ventricular mass increased with age in nonpregnant rats and increased with pregnancy only in young rats. Compared with young pregnant rats, the aortic ejection time of aged pregnant rats was greater and Tei index was lower. Overall, the greater aortic ejection time and lower Tei index with age in pregnant rats suggest mildly altered cardiac adaptations to pregnancy with advanced maternal age, which may contribute to adverse outcomes in advanced maternal age pregnancies.NEW & NOTEWORTHY We demonstrated that even before the age of reproductive senescence, rats show signs of age-related alterations in cardiac structure that suggests increased cardiac work. Our data also demonstrate, using an in vivo echocardiographic approach, that advanced maternal age in a rat model is associated with altered cardiac function and structure relative to younger pregnant controls.

The TTN p. Tyr4418Ter mutation causes cardiomyopathy in human and mice.

To generate a mouse model carrying TTNtv Y4370* simulating the newly discovered human heterozygous nonsense TTNtv c.13254T>G (p.Tyr4418Ter) to supplement and improve the functional evidence of pathogenic mutation TTNtv c.13254T>G on the pathogenic type of dilated cardiomyopathy. We generated 4 mice carrying TTNtv p. Y4370* through CRISPR/Cas-mediated genome engineering. Monthly serological detection, bimonthly echocardiography, and histology evaluation were carried out to observe and compare alterations of cardiac structure and function between 4 TTN+/- mice and 4 wild-type (WT) mice. For the two-month-old TTN+/- mice, serum glutamic-oxalacetic transaminase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) were significantly increased, the diastolic Left Ventricular Systolic Anterior Wall (LVAW), and the LV mass markedly rose, with the left ventricular volume displaying an increasing trend and Ejection Fraction (EF) and Fractional Shortening (FS) showing a decreasing trend. Besides, the histological evaluation showed that cardiac fibrosis level and positive rate of cardiac mast cell of TTN+/- mice were obviously increased compared with WT mice. TTNtv Y4370* could lead to cardiac structure and function alterations in mice, supplementing the evidence of TTNtv c.13254T>G pathogenicity in human.

A Self-Homing and Traceable Cardiac Patch Leveraging Ferumoxytol for Spatiotemporal Therapeutic Delivery.

Mesenchymal stem cell (MSC)-based cardiac patches are envisioned to be a promising treatment option for patients with myocardial infarction. However, their therapeutic efficacy and duration are hampered due to their limited retention on the epicardium. We engineered a scaffold-free MSC sheet with an inherent ability to migrate into the infarcted myocardium, a strategy enabled by actively establishing a sustained intracellular hypoxic environment through the endocytosis of our FDA-approved ferumoxytol. This iron oxide nanoparticle stabilized hypoxia-induced factor-1α, triggering upregulation of the CXC chemokine receptor and subsequent MSC chemotaxis. Thus, MSCs integrated into 2/3 depth of the left ventricular anterior wall in a rat model of acute myocardial infarction and persisted for at least 28 days. This led to spatiotemporal delivery of paracrine factors by MSCs, enhancing cardiac regeneration and function. Ferumoxytol also facilitated the noninvasive MRI tracking of implanted MSCs. Our approach introduces a strategy for mobilizing MSC migration, holding promise for rapid clinical translation in myocardial infarction treatment.

Distant myocardial infarction: a case report

Currently, more and more cases of distant myocardial infarction are being registered. This pathological condition occurs due to an acute decrease in myocardial blood supply, which was provided by a donor artery, which blood supply system is anatomically not directly connected to the affected area. Cases of distant myocardial infarction are sporadic. Therefore, there are difficulties in choosing the right management strategy. During percutaneous coronary intervention, it is possible to perform recanalization of an artery with chronic occlusion, which anatomically supplies blood to the affected wall, and/or donor artery stenting, which supplies the infarction zone due to collaterals. The article presents a case of non-Q wave myocardial infarction of left ventricular anterior wall, which developed in a patient with 90% stenosis in the proximal left anterior descending (LAD) artery, chronic occlusion of the middle LAD segment, and 80% stenosis in the proximal right coronary artery. Direct stenting of the right coronary artery led to a significant increase in the contrast intensity in intersystem collaterals from the posterior interventricular artery to LAD artery. This was accompanied by an improvement in the clinical symptoms and a complete absence of angina throughout the patient’s hospital stay.

Gene-Specific Discriminative Echocardiogram Findings in Hypertrophic Cardiomyopathy Determined Using Artificial Intelligence: A Pilot Study

Hypertrophic cardiomyopathy (HCM) is among the most common forms of cardiomyopathies, with a prevalence of 1:200 to 1:500 people. HCM is caused by variants in genes encoding cardiac sarcomeric proteins, of which a majority reside in MYH7, MYBPC3, and TNNT2. Up to 40% of the HCM cases do not have any known HCM variant. Genotype–phenotype associations in HCM remain incompletely understood. This study involved two visits of 46 adult patients with a confirmed diagnosis of HCM. In total, 174 genes were analyzed on the Next-Generation Sequencing platform, and transthoracic echocardiography was performed. Gene-specific discriminative echocardiogram findings were identified using the computer vision library Fast AI. This was accomplished with the generation of deep learning models for the classification of ultrasonic images based on the underlying genotype and a later analysis of the most decisive image regions. Gene-specific echocardiogram findings were identified: for variants in the MYH7 gene (vs. variant not detected), the most discriminative structures were the septum, left ventricular outflow tract (LVOT) segment, anterior wall, apex, right ventricle, and mitral apparatus; for variants in MYBPC3 gene (vs. variant not detected) these were the septum, left ventricle, and left ventricle/chamber; while for variants in the TNNT2 gene (vs. variant not detected), the most discriminative structures were the septum and right ventricle.

Forensic Pathological Diagnosis of Acute and Old Myocardial Infarction Using Fourier Transform Infrared Spectroscopy.

Fourier transform infrared spectroscopy (FTIR) was used to analyze myocardial infarction tissues at different stages of pathological change to achieve the forensic pathology diagnosis of acute and old myocardial infarction. FTIR spectra data of early ischemic myocardium, necrotic myocardium, and myocardial fibrous tissue in the left ventricular anterior wall of the sudden death group of atherosclerotic heart disease and the myocardium of the normal control group were collected using hematoxylin-eosin (HE) and immunohistochemistry (IHC) staining as a reference, and the data were analyzed using multivariate statistical analysis. The mean normalized spectra of control myocardium, early ischemic myocardium and necrotic myocardium were relatively similar, but the mean second derivative spectra were significantly different. The peak intensity of secondary structure of proteins in early ischemic myocardium was significantly higher than in other types of myocardium, and the peak intensity of the α-helix in necrotic myocardium was the lowest. The peaks of amide Ⅰ and amide Ⅱ in the mean normalized spectra of myocardial fibrous tissue significantly shifted towards higher wave numbers, the peak intensities of amide Ⅱ and amide Ⅲ were higher than those of other types of myocardium, and the peak intensities at 1 338, 1 284, 1 238 and 1 204 cm-1 in the mean second derivative spectra were significantly enhanced. Principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) showed that FTIR could distinguish different types of myocardium. FTIR technique has the potential to diagnose acute and old myocardial infarction, and provides a new basis for the analysis of the causes of sudden cardiac death.

Distribution of proteinase K-resistant anti-α-synuclein immunoreactive axons in the cardiac plexus is unbiased to the left ventricular anterior wall.

Lewy body disease (LBD) is characterized by the appearance of Lewy neurites and Lewy bodies, which are predominantly composed of α-synuclein. Notably, the cardiac plexus (CP) is one of the main targets of LBD research. Although previous studies have reported obvious differences in the frequency of Lewy body pathology (LBP) in the CP, none of them have confirmed whether LBP preferably appears in any part of the CP. Thus, we aimed to clarify the emergence and/or propagation of LBP in the CP. In this study, 263 consecutive autopsy cases of patients aged ≥50 years were included, with one region per case selected from three myocardial perfusion areas (MPAs) and subjected to proteinase K and then immunohistochemically stained with anti-α-synuclein antibodies to assess LBP. We stained all three MPAs in 17 cases with low-density LBP and observed the actual distribution of LBP. LBP were identified in the CP in 20.2% (53/263) of patients. Moreover, we found that LBP may appear in only one region of MPAs, mainly in the young-old group (35.3% (6/17) of patients). These findings suggest that it is possible to underestimate LBP in the CP, especially in the young-old group, by restricting the search to only one of the three MPAs.

Arrhythmic risk stratification in patients with left ventricular ring-like scar

Abstract Background Myocardial fibrosis assessment with late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has recently emerged as an independent predictor of major adverse events in patients with non-ischemic cardiomyopathy. Several studies have examined different locations and extension degrees of LGE, and the so called "ring-like pattern" has been related with an increased incidence of ventricular arrhythmias, in patients with dilated cardiomyopathy (DCM), but also in patients with preserved systolic function. Purpose To describe clinical, electrocardiographic, echocardiographic, CMR and genetic features of the left ventricular (LV) ring-like scar phenotype and to evaluate which characteristics may be associated with the risk of sudden cardiac death (SCD). Methods Patients diagnosed with LV ring-like scar were identified at 6 referral Centres. Diagnosis was based on: 1) ring-like LGE LV pattern, defined as at least 3 contiguous segments with subepicardial/midwall LGE in the same slice with or without fatty infiltration; or 2) pathology examination of explanted hearts/autoptic cases suffering from sudden cardiac death (SCD). Moreover, patients must have an additional inclusion criterion: a positive genetic test, or ≥1 patient in the same family with an ascertained cardiomyopathy. Major adverse arrhythmic cardiac events (MAACE), defined as a composite of SCD, aborted SCD, and sustained ventricular tachycardia (SVT), were the primary study endpoint. Results The final cohort comprised 129 patients (male 59.7%, median age at diagnosis 44 years). During a median follow-up of 3.4 years (IQR 1.2 – 64.), MAACE occurred in 31 patients (24%). Nearly 70% of the patients had a likely pathogenic/pathogenic mutation, mostly in desmoplakin (DSP) and filamin-C (FLNC) genes (65% and 19%, respectively). Sex, QRS width, and LGE in LV anterior wall and/or apex, were the only independent predictors of the outcome events (HR: 0.329, 95% CI: 0.119-0.916, P = 0.033; HR: 1.036, 95% CI 1.019-1.053, P < 0.001; HR 4.270, 95% CI 1.337-13.630, P = 0.014, respectively). A significant interaction between sex and LGE in anterior wall/apex was observed, being this regions associated with MAACE only in male patients (p for interaction = 0.033). Although related to the arrhythmic endpoint at the Kaplan-Meier survival curves, neither DCM echocardiographic phenotype, nor LV ejection fraction ≤35% remained statistically associated to MAACE at the multivariate analysis. Age, genetic mutations, right ventricular involvement, proband status, LV-LGE extension (number of segments) were not statistically related to the study endpoint. Conclusions In this selected cohort of patients with LV ring-like scar and either a genetic test or family history, malignant arrhythmic events were predicted by male sex, QRS width and LGE in anterior wall and/or apex.Graphical Abstract

Regulation of BACH1 expression by hemin improves cardiac function and revascularisation in a mouse model of myocardial infarction

Abstract Therapies to induce mature neovascularization formation and moderate oxidative stress after myocardial infarction (MI) are urgently needed. The BACH1 transcription factor is known as a repressor of genes involved in the antioxidant response (1). We have demonstrated BACH1 can regulate neovascularization through modulation of pro-angiogenic genes, particularly angiopoietin-1 (2). We hypothesise expression of BACH1 after MI contributes to suppression of genes which promote reparative angiogenesis. We propose treatment with hemin (a therapeutic compound known to degrade BACH1) will prevent BACH1 repression of target genes, leading to increased expression of proangiogenic factors and increased neovascularisation and cardiac repair in a mouse MI model. MI was induced in 8-week old C57/Bl6 male mice by permanent ligation of the left anterior descending coronary artery, n=10-14. Expression of Bach1 and the antioxidant Hmox1 in heart tissue was determined by Western blot at day 3 and 10 post MI, whilst a second group were randomized to receive vehicle, 12.5, 25 or 50mg/kg hemin intraperitoneally every 3 days until 28 days post-MI. On day 28, following echocardiography, mice were euthanised and ventricular tissue collected for histological analysis. Data was analysed by 2-way ANOVA with post-test multiple comparisons. Compared to sham mice, Bach1 expression significantly increased at both day 3 and 10 post MI (P<0.0001 and P<0.01 respectively). Bach1 expression at day 10 was significantly lower compared to day 3, suggesting a transient effect (P<0.01). Hmox1 expression was significantly decreased at both timepoints (both P<0.001 vs. sham) suggesting in the initial period after MI the antioxidant and angiogenic responses are suboptimal. Treatment of mice with 25mg/kg hemin for 28 days post MI caused significant increases in capillary and arteriole density in the peri-infarct zone (P<0.0002 and P<0.0008 vs. vehicle respectively). There was no effect on capillary or arteriole density in the remote zone. In vehicle-treated mice there was thinning of the left ventricular end-diastolic anterior wall thickness (LVAW) corresponding to the infarct area. Interestingly, a significant increase in the thickness of the LVAW was observed after 25mg/kg hemin treatment (P<0.0001 vs. vehicle), whilst LV internal diameter significantly decreased (P<0.0001 vs. vehicle). Ejection fraction (P<0.0001), fractional shortening (P<0.0009) and stroke volume (P<0.0001) all significantly increased in mice treated with hemin compared to vehicle. Treatment of mice with 25mg/kg hemin for 28 days post MI was sufficient to induce significantly increased capillary and arteriole density in the peri-infarct region. We also observed hemin exerted benefits on volumetric and contractility indexes. This data suggests hemin has potential to be used therapeutically post MI to improve revascularisation and cardiac function.

Abstract 18374: Effective Atomic Number and Electron Density Number Acquired Using Latest Spectral CT Enable the Differentiation of Infarcted Myocardium and Hypertrophied Myocardium From Normal Myocardium

Introduction: Spectral CT can acquire effective atomic (EAN) and electron density number (EDN). Hypothesis: EAN and EDN using spectral CT enable the differentiation of infarcted myocardium and hypertrophied myocardium from normal myocardium. Methods: We analyzed 146 patients (73 males; mean age 55 ± 14 years old) who had no significant coronary stenosis on CT (7500; Philips) and normal ECG (normal group), 20 patients with previous myocardial infarction (MI) (12 males; mean age 73 ± 7 years old) (MI group), and 10 patients with hypertrophic cardiomyopathy (HCM) (5 males; mean age 66 ± 15 years old) (HCM group). On CT, we measured EAN and EDN in the interventricular septum (IVS), left ventricular (LV) anterior wall (LVAW), and lateral wall (LVLW) within a 1.0 mm2 circle at LV inflow level in the non-contrast and early contrast phase. In MI and HCM groups, EAN and EDN were also measured in the infarcted and hypertrophied myocardium, respectively. Results: In the non-contrast and early contrast phase, the EAN was significantly lower in the infarcted myocardium group than in the normal group (p < 0.01), in the non-infarcted myocardium than in the MI group (p < 0.05) and non-hypertrophied myocardium in the HCM group (p < 0.05), and in the hypertrophic myocardium in the HCM group than in the normal group (p < 0.05) and non-hypertrophic myocardium in the HCM group (p < 0.05). In the non-contrast and early contrast phase, the EDN was also lower in the infarcted myocardium than in the normal group (p < 0.01), non-infarcted myocardium in the MI group (p < 0.05), hypertrophied and non-hypertrophied myocardium in the HCM group (p < 0.05). Conclusion: The use of EAN and EDN enables the differentiation of infarcted myocardium (EAN and EDN) and hypertrophied myocardium (EAN) from normal myocardium even on non-contrast CT alone. The use of EAN and EDN enables the detection of abnormal myocardial characteristics (blood flow decrement, fibrotic change, hypertrophy, and inflammation) on non-contrast CT alone.

Abstract 13816: Clearing P16+ Cells Prevents Cardiac Dysfunction and Death in Mice With Acute Myocardial Infarction

Introduction: Cellular senescence, a stress and age-related response, is often characterized by p16 expression in p16 positive (p16 + ) senescent cells. Senescent cells secrete profibrotic and proinflammatory factors as parts of a “senescence associated secretory phenotype”. The role of cellular senescence in myocardial infarction (MI) is unclear. Aims: To study the effect of p16 + cell clearance on survival, cardiac remodeling and function after MI. Methods: We used INK ATTAC transgenic mice, in which p16 + cells undergo targeted apoptosis upon exposure to a dimerizer, AP20187 (AP). MI mice were treated with AP or vehicle (V), twice a week for 1 month, beginning 3-4 hours post-MI. Cardiac function and structure were evaluated with echocardiography, hemodynamic parameters with a Millar catheter, infarct area with Masson’s Trichrome, gene expression with qPCR and single-nucleus RNA-sequencing (snRNAseq). Results: Survival post MI was dramatically increased in MI-AP vs MI-V mice (P<0.001, Fig A), primarily via prevention of cardiac rupture (CardRup). Left ventricular (LV) ejection fraction (EF%) and LV anterior wall thickness at end diastole (LVAWd) decreased in MI-V vs Sham and improved in MI-AP mice (Fig B), indicating preservation of cardiac function and structure with p16 + cell clearance. Hemodynamic indices of LV function (max and min dP/dt) improved with AP (Fig C). Fibrosis-related gene expression (Col1a1, Col3a1 and Lox; Fig D) increased with MI and improved with AP, paralleling changes in infarct size (Fig E). snRNAseq showed that genes were principally upregulated in MI-V macrophages and neutrophils; significant responses were seen in TNF-α, inflammatory response pathways and gene programs associated with CardRup (Fig F). Conclusion: These results suggest that p16 + cells play a significant role in the evolution of MI, apparently by modulating inflammatory signaling, pointing to an important pathophysiological role of cellular senescence.

Abstract 13336: Myocardial Protection of Chitosan Cardiac Muscle Patch in Myocardial Infarcted Mice

Background: Poor grafted rate of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) via direct injection into the myocardium limits the efficacy of cardiac repair after myocardial infarction (MI). Chitosan-based scaffolds has regarded as functional biomaterial for designing delivery systems in cardiac therapies. This study aimed to enhancing the potency of cardiac repair with the hiPSC-CMs loaded chitosan cardiac patch (hCCMP). Methods: The patches were fabricated with chitosan. Characterization of the chitosan patches was evaluated through the detection of swelling rate and porosity. Biocompatibility of the hiPSC-CMs loaded patches was analysed by scanning electron microscope (SEM) and CCK8 assay. The mice were randomly divided into 4 groups (n=10 for each). Animals underwent MI-inductive surgery followed by epicardium implantation of hCCMP or Empty-patch (without hiPSC-CMs); Sham and MI mice without further intervention were set as control. 4 weeks after MI, heart function was measured via echocardiography. Engraftment was evaluated with human cardiac troponin T staining. Infarction size, left ventricular anterior wall thickness, cardiac remodeling, angiogenesis, arterialization and apoptosis was detected via immunofluorescence in infarcted boder area. Results: SEM showed that the chitosan patch had regular pore size and good 3D structure; porosity was about (96.7±0.37)%. On day3, the patch swelling rate was about (715±64.55)%. SEM, CCK8 assay showed a normal cells growth in the chitosan patch. The hiPSC-CMs grafted well with chitosan patch delivery systems and was associated with significantly improvement in LV heart function, infarction size, LV anterior wall thickness, cardiac remodeling, angiogenesis and cardiomyocyte apoptosis 4 weeks after MI. Conclusions: The 3D chitosan cardiac patch with hiPSC-CMs loaded can enhance the potency of cardiac repair after MI and present a novel and promising therapic strategy.

The simultaneous occurrence of paraganglioma, Takotsubo syndrome, and Markis type I coronary artery ectasia in the same patient is a rare, high-risk clinical syndrome: a case report

BackgroundPopulation-wide, paraganglioma (PGL) is uncommon. The incidence of Takotsubo syndrome (TTS) ranges from 0.5% to 0.9% and also is an exceedingly rare manifestation of PGL. Coronary artery ectasia (CAE) is also uncommon, with an incidence ranging from 1.2% to 4.9%. Herein, we present a case of PGL, TTS, and Markis type I CAE that occured in the same patient.Case presentationA man in his early 40s was admitted to our hospital with a 16-hour history of abdominal colic. Computed tomography and laboratory examination led to the diagnosis of PGL, coronary angiography led to the diagnosis of Markis type I or Chinese type III CAE, and two echocardiographic examinations led to the diagnosis of TTS. When the patient was treated by phenoxybenzamine instead of surgery for the PGL, his blood pressure and glucose level gradually returned to normal. The CAE was treated by thrombolysis, antiplatelet medications, atorvastatin, and myocardial protection therapies. No symptoms of PGL, CAE, or TTS were seen during a 6-month follow-up, and the patient had an excellent quality of life. We confirmed that phenoxybenzamine was the cause of the TTS because paradoxical systolic motion of the apex, inferior wall, left ventricular anterior wall, and interventricular septum were similarly recovered when the PGL was treated by phenoxybenzamine.ConclusionsTo raise awareness of this illness and prevent misdiagnosis, we have herein presented a case of TTS that was brought on by PGL with Markis type I CAE for clinicians’ reference. In addition, in clinical practice, we should consider the possibility of a concomitant coronary artery disease even if the TTS is caused by a PGL-induced catecholamine surge.

Assessment of subclinical left ventricular myocardial systolic dysfunction in type 2 diabetes mellitus patients with or without hypertension by global and segmental myocardial work

ObjectiveThe research was aimed to evaluate the subclinical left ventricular (LV) myocardial systolic dysfunction in T2DM patients with or without hypertension (HT) by global and segmental myocardial work (MW).MethodsA total of 120 T2DM patients (including 60 T2DM patients with HT) and 70 sex- and age- matched normal controls were included. The global and segmental variables of work index (WI), constrictive work (CW), waste work (WW), work efficiency (WE), and CW/WW were analysed by non-invasive pressure-strain loop. Receiver operating characteristic (ROC) analysis was performed for detection the subclinical LV systolic dysfunction in T2DM patients with and without HT.ResultsThe global work index (GWI), global CW (GCW), global WE (GWE), and GCW/global WW (GWW) of T2DM and T2DM patients with HT were significantly lower than normal controls (p < 0.05). The WI, CW, WE, and CW/WW of the LV anterior wall in T2DM and T2DM patients with HT were significantly lower when compared with those of the normal controls (p < 0.05). ROC analysis showed that the value of area under the curve (AUC) in combined GWI, GCW, GWE, and GCW/GWW was significantly higher than the AUCs of the individual indices (p < 0.05).ConclusionsMW can non-invasively and accurately evaluate subclinical global and segmental LV myocardial systolic dysfunction in T2DM patients with and without HT. Regulating total cholesterol levels and controlling blood pressure in T2DM patients with and without HT might reduce the impairment of LV myocardial systolic function.

Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway

To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway. Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were determined. Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05). CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1β and IL-6 in myocardial tissue.

Wellens’ syndrome in clinical practice

Despite the declining cardiovascular mortality, the incidence of myocardial infarction (MI) is still high, and therefore the issues of its timely diagnosis remain extremely relevant. In addition to the main diagnostic criteria and typical electrocardiographic (ECG) signs, there are many secondary patterns that suggest MI. Wellens’ syndrome (WS) is one of these ECG patterns, which indicates that the patient is at high risk of left ventricular anterior wall MI, caused by occlusion of the anterior interventricular artery (AIA) or its critical stenosis. Despite the relatively low incidence of WS, it is necessary to increase physicians’ awareness in order to prevent MI and reduce its possible negative consequences.This article presents clinical cases of WS, which show the importance of its diagnosis in the management of patients with anginal pain. The first patient is 43-year-old with a diagnosis of class III exertional angina, a history of anginal pain, and the presence of inverted T waves in V2-V3 leads. AIA stenting was performed on the 7th day of hospitalization. The second patient is 67-year-old with a similar diagnosis and history, biphasic T waves in I, aVL, V1-V3 and V5-V6 leads, deeply inverted T waves in V4. Stenting of the AIA and right coronary artery (RCA) was performed on days 5-6 after the most severe episode of anginal pain and after the anginal pain became recurrent. In both cases, WS was not diagnosed. The third patient, 57-year-old, with T wave inversion in II, III, aVF, leads ST segment elevation of less than 1 mm in lead III, minimal ST segment depression in aVL and V2-V3 leads, followed in less than 2 hours by ST segment elevation in II, III, aVF leads. In this patient, WS was diagnosed in a timely manner, urgent coronary angiography was performed, 99% RCA stenosis was detected, and RCA stenting was performed. The outcome is left ventricular inferior wall non-Q wave MI. The last cited case of WS indicates that this syndrome develops not only with AIA damage, but also with damage to other coronary arteries.

Role of radionuclide assessment of global and regional mechanical dyssynchrony of the heart in prognosis of cardiac resynchronization therapy in patients with heart failure

Aim. To determine the prognostic significance of cardiac regional mechanical dyssynchrony (MD), assessed by radionuclide equilibrium ventriculography (REVG) in candidates for cardiac resynchronization therapy (CRT).Material and methods. The study included 65 patients with indications for CRT according to current guidelines. Prior to CRT, all patients underwent REVG to assess cardiac contractile function and MD. According to the phase analysis, indicators of global and regional cardiac MD were evaluated: phase standard deviation (PSD), histogram band width (HBW), entropy, and interventricular dyssynchrony. The regional assessment included an evaluation of phase histograms obtained from the analysis of the contraction of certain walls: left ventricular (LV) anterior, lateral, posterior wall, right ventricular (RV) free wall, and the interventricular septum. To evaluate the effectiveness of treatment 6 months after CRT, all patients underwent echocardiography, on the basis of which patients were divided into groups of responders and non-responders.Results. REVG revealed significant differences in the initial regional MD values between the groups of responders and non-responders: in responders, MD values of RV free wall (PSD: 39 (28-67) vs 28 (20-50), p=0,03) and LV anterior wall (PSD: 28,5 (16-40) vs 14 (11-24), p=0,0005) were higher, and the LV lateral wall was lower (PSD: 10 (7-14) vs 15 (9-26), p=0,007) than in non-responders. Multivariate logistic regression found following independent predictors of a positive response to CRT: heart failure of ischemic origin, LV HBW, RV free wall PSD, anterior wall PSD, LV lateral wall HBW (p&lt;0,001). The sensitivity and specificity of the model was 93% and 91%, respectively.Conclusion. Regional MD scintigraphy parameters increase the predictive value of REVG in CRT candidates. The most informative in this regard are the PSD of RV free wall and LV anterior wall, as well as the HBW of LV lateral wall.

Myocardial deformation imaging by 2D speckle tracking echocardiography for assessment of diastolic dysfunction in murine cardiopathology

Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.

Relationship between left ventricular mechanical dyssynchrony with cardiac resynchronization therapy response in chronic heart failure patients with left bundle branch block

Aim. To investigate the relationship between left ventricular (LV) mechanical dyssynchrony with cardiac resynchronization therapy (CRT) response in chronic heart failure (CHF) pts with left bundle branch block.Methods. Forty-nine pts (male - 34 [69.4%], average age 58.3±11.4 years) with sinus rhythm, permanent left bundle branch block with QRS duration ≥150 ms and New York Heart Association (NYHA) II-III functional class of CHF were included in the study. In addition to full examination, myocardial perfusion scintigraphy (MPS) and gated blood pool single-photon emission computed tomography (gBPS) were performed before and 6 months after CRT devices with cardioverter-defibrillator function implantation. Pts were considered as responders to CRT if they fulfilled after 6-month follow-up the following combined criteria: NYHA FC improvement ≥1 class + LV end systolic volume decrease &gt;15% or NYHA FC improvement ≥1 class + LV ejection fraction improvement &gt;5%.Results. The 1st and 2nd groups included 35 (71.4%) and 14 (28.6%) pts with and without response to CRT respectively. Groups were comparable in terms of pre-CRT implantation clinical and instrumental parameters, except for MPS and gBPS parameters. The multivariate logistic regression had shown that only ∆interventricular dyssynchrony (adjusted odds ratio [OR] 1,0349; 95% confidence interval [CI] 1.0075-1,0631; р=0.01) and phase standard deviation of the anterior LV wall (OR 1.0669; 95% CI 1.0118-1.1251; p=0.01) were independently related with CRT response. An increase in the prognostic coefficient, calculated using the ∆interventricular dyssynchrony and phase standard deviation of the anterior LV wall, more than 0.67 was a predictor of CRT response (area under the curve 0.918; sensitivity 85.71; specificity 85.71; p &lt;0.001).Conclusion. The mechanical dyssynchrony assessed by MPS and gBPS is associated with CRT response. According to our predictive model, an increase in prognostic coefficient more than 0.67 is a predictor of CRT response.

Dose additive maternal and offspring effects of oral maternal exposure to a mixture of three PFAS (HFPO-DA, NBP2, PFOS) during pregnancy in the Sprague-Dawley rat

Simultaneous exposure to multiple per- and polyfluoroalkyl substances (PFAS) is common in humans across the globe. Individual PFAS are associated with adverse health effects, yet the nature of mixture effects after exposure to two or more PFAS remains unclear. Previously we reported that oral administration of hexafluoropropylene oxide-dimer acid (HFPO-DA, or GenX), Nafion byproduct 2 (NBP2), or perfluorooctane sulfonate (PFOS) individually during pregnancy produced maternal and F1 effects. Here, we hypothesized that responses to the combined exposure to these three PFAS would be dose additive. Pregnant Sprague-Dawley rats were exposed to a fixed-ratio equipotent mixture where the top dose contained each PFAS at their ED50 for neonatal mortality (100 % dose = PFOS 3 mg/kg; NBP2 10 mg/kg; HFPO-DA 110 mg/kg), followed by a dilution series (33.3, 10, 3.3, and 1 %) and vehicle controls (0 % dose). Consistent with the single chemical studies, dams were exposed from gestation day (GD)14–18 or from GD8-postnatal day (PND2). Fetal and maternal livers on GD18 displayed multiple significantly upregulated genes associated with lipid and carbohydrate metabolism at all dose levels, while dams displayed significantly increased liver weight (≥3.3 % dose) and reduced serum thyroid hormones (≥33.3 % dose). Maternal exposure from GD8-PND2 significantly reduced pup bodyweights at birth (≥33.3 % dose) and PND2 (all doses), increased neonatal liver weights (≥3.3 % dose), increased pup mortality (≥3.3 % dose), and reduced maternal bodyweights and weight gain at the top dose. Echocardiography of adult F1 males and females identified significantly increased left ventricular anterior wall thickness (~10 % increase), whereas other cardiac morphological, functional, and transcriptomic measures were unaffected. Mixture effects in maternal and neonatal animals conformed to dose addition using a relative potency factor (RPF) analysis. Results support dose addition-based cumulative assessment approaches for estimating combined effects of PFAS co-exposure.