Ventricle Muscle Research Articles

Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors

Allosteric modulation is a central mechanism for metabolic regulation but has yet to be described for a gut microbiota-host interaction. Phenylacetylglutamine (PAGln), a gut microbiota-derived metabolite, has previously been clinically associated with and mechanistically linked to cardiovascular disease (CVD) and heart failure (HF). Here, using cells expressing β1- versus β2-adrenergic receptors (β1AR and β2AR), PAGln is shown to act as a negative allosteric modulator (NAM) of β2AR, but not β1AR. In functional studies, PAGln is further shown to promote NAM effects in both isolated male mouse cardiomyocytes and failing human heart left ventricle muscle (contracting trabeculae). Finally, using in silico docking studies coupled with site-directed mutagenesis and functional analyses, we identified sites on β2AR (residues E122 and V206) that when mutated still confer responsiveness to canonical β2AR agonists but no longer show PAGln-elicited NAM activity. The present studies reveal the gut microbiota-obligate metabolite PAGln as an endogenous NAM of a host GPCR.

Mechanisms of myosin, myofibril, and cardiomyocyte dysfunction with the MYH7 R403Q mutation in porcine ventricle muscle

Mechanisms of myosin, myofibril, and cardiomyocyte dysfunction with the MYH7 R403Q mutation in porcine ventricle muscle

Evaluation of Mean “R” Wave Amplitude in Lead V1 of Electrocardiogram among Term Newborn Infants in Tertiary Care Institution in South India

Background: The changes in the left ventricle to right ventricle muscle mass ratio account for the majority of the age-related changes in pediatric electrocardiograms (ECGs). A newborn's right ventricle muscle mass is more than the newborn's left ventricle. Physiologically, newborn infants have a dominant right ventricle. Race differences in QRS voltage normal values exist. Compared to Euro-Americans, African-Americans have a higher upper normal limit of QRS voltages. Typically, right ventricular hypertrophy is seen in newborns. To distinguish between pathological and physiological newborn hypertrophy, it is critical to measure the mean QRS amplitude in healthy newborns. This is the first study on the Indian population, with previous ones being conducted among African-Americans. Methodology: Between 2015 and 2016, this prospective observational study was carried out in the pediatrics department of a tertiary care facility in India. The study included 76 term newborns who were under 3 days old. In Chennai's Kilpauk Medical College and Hospital, the newborn infants underwent clinical examinations as well as echocardiography before receiving their ECGs. A baseline questionnaire that had been previously created was used for data collection. Results: For the Indian population, the mean R wave amplitude was 11.56 mm, with a standard deviation of 2.96 mm, and the 5th and 95th percentiles were 6.85 mm and 16.15 mm, respectively. The Fridericia formula for the mean QTc interval gives a value of 357.14 ms, a standard deviation of 34.072 ms, and a 95% confidence interval of 349.36–364.93 ms. Since a newborn's heart rate typically exceeds 100 beats/min, the measurement of QTc using the Fridericia formula more accurately predicts QTc in the newborn. The mean heart rate was 125.75 beats/min, with a standard deviation of 15.44 beats/min, and the 5th and 95th percentiles were 93.7 and 149 beats/min, respectively. Conclusions: The “R” wave mean amplitude in lead V1 was 11.56 mm, with a 2.96 mm standard deviation; the fifth and ninety-fifth percentiles, respectively, were 6.85 mm and 16.15 mm. The population's “R” wave in the lead V1 exhibits racial differences in amplitude.

Exercise-induced angiogenesis is attenuated by captopril but maintained under perindopril treatment in hypertensive rats.

Angiogenesis is an important exercise-induced response to improve blood flow and decrease vascular resistance in spontaneously hypertensive rats (SHR), but some antihypertensive drugs attenuate this effect. This study compared the effects of captopril and perindopril on exercise-induced cardiac and skeletal muscle angiogenesis. Forty-eight Wistar rats and 48 SHR underwent 60 days of aerobic training or were kept sedentary. During the last 45 days, rats were treated with captopril, perindopril or water (Control). Blood pressure (BP) measurements were taken and histological samples from the tibialis anterior (TA) and left ventricle (LV) muscles were analyzed for capillary density (CD) and vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and endothelial nitric oxide synthase (eNOS) protein level. Exercise increased vessel density in Wistar rats due to higher VEGFR-2 (+17%) and eNOS (+31%) protein level. Captopril and perindopril attenuated exercise-induced angiogenesis in Wistar rats, but the attenuation was small in the perindopril group, and this response was mediated by higher eNOS levels in the Per group compared to the Cap group. Exercise increased myocardial CD in Wistar rats in all groups and treatment did not attenuate it. Both exercise and pharmacological treatment reduced BP of SHR similarly. Rarefaction was found in TA of SHR compared to Wistar, due to lower levels of VEGF (-26%) and eNOS (-27%) and treatment did not avoid this response. Exercise prevented these reductions in control SHR. While rats treated with perindopril showed angiogenesis in the TA muscle after training, those rats treated with captopril showed attenuated angiogenesis (-18%). This response was also mediated by lower eNOS levels in Cap group compared with Per and control group. Myocardial CD was reduced in all sedentary hypertensive compared with Wistar and training restored the number of vessels compared with sedentary SHR. In conclusion, taken into account only the aspect of vessel growth, since both pharmacological treatments reduced BP in SHR, the result of the present study suggests that perindopril could be a drug of choice over captopril for hypertensive practitioners of aerobic physical exercises, especially considering that it does not attenuate angiogenesis induced by aerobic physical training in skeletal and cardiac muscles.

Function of left ventricle mitochondria in highland deer mice and lowland mice.

To gain insight into the mitochondrial mechanisms of hypoxia tolerance in high-altitude natives, we examined left ventricle mitochondrial function of highland deer mice compared with lowland native deer mice and white-footed mice. Highland and lowland native deer mice (Peromyscus maniculatus) and lowland white-footed mice (P. leucopus) were first-generation born and raised in common lab conditions. Adult mice were acclimated to either normoxia or hypoxia (60kPa) equivalent to ~ 4300m for at least 6weeks. Left ventricle mitochondrial physiology was assessed by determining respiration in permeabilized muscle fibers with carbohydrates, lipids, and lactate as substrates. We also measured the activities of several left ventricle metabolic enzymes. Permeabilized left ventricle muscle fibers of highland deer mice showed greater rates of respiration with lactate than either lowland deer mice or white-footed mice. This was associated with higher activities of lactate dehydrogenase in tissue and isolated mitochondria in highlanders. Normoxia-acclimated highlanders also showed higher respiratory rates with palmitoyl-carnitine than lowland mice. Maximal respiratory capacity through complexes I and II was also greater in highland deer mice but only compared with lowland deer mice. Acclimation to hypoxia had little effect on respiration rates with these substrates. In contrast, left ventricle activities of hexokinase increased in both lowland and highland deer mice after hypoxia acclimation. These data suggest that highland deer mice support an elevated cardiac function in hypoxia, in part, with high ventricle cardiomyocyte respiratory capacities supported by carbohydrates, fatty acids, and lactate.

Superior cardiometabolic and cellular adaptive responses to multiple versus single daily sessions of high-intensity interval training in Wistar rats

This study aimed to compare in rats the cardiometabolic and cellular adaptative responses to 8 weeks of high-intensity interval training (HIIT) performed in a single (1xHIIT) or three shorter daily sessions (3xHIIT). Male Wistar rats were assigned to untrained (n = 10), 1xHIIT (n = 10), and 3xHIIT (n = 10) groups. Both HIIT groups performed 15 min of a treadmill run five times per week for 8 weeks. The 1xHIIT performed single daily sessions of 15 min, and the 3xHIIT performed three daily sessions of 5 min with an interval of 4 h between sessions. Resting VO2 and VO2max were measured using a metabolic chamber; blood pressure and heart rate were measured by plethysmography; body composition was estimated by DEXA; Glucose and insulin tolerance tests were performed; after euthanasia, hearts, gastrocnemius, and visceral fat were harvested for analysis of cardiac function, histology, and morphology. Mitochondrial densities of the gastrocnemius and left ventricle muscles were determined by electron microscopy. 3xHIIT induced similar positive adaptative responses to 1xHIIT on resting VO2 and VO2max, cardiac function, and mitochondria density. 3xHIIT was superior to 1xHIIT in reducing visceral fat weight and adipocyte size and improving insulin tolerance. Multiple short daily bouts of HIIT may be superior to single HIIT daily sessions in improving cardiometabolic and cellular adaptations in rats.

Heterozygous SOD2 deletion selectively impairs SERCA function in the soleus of female mice.

The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) restores intracellular Ca2+ ([Ca2+]i) to resting levels after muscle contraction, ultimately eliciting relaxation. SERCA pumps are highly susceptible to tyrosine (T)‐nitration, impairing their ability to take up Ca2+ resulting in reduced muscle function and increased [Ca2+]i and cellular damage. The mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2), converts superoxide radicals into less reactive H2O2. Heterozygous deletion of SOD2 (Sod2 +/−) in mice increases mitochondrial oxidative stress; however, the consequences of reduced SOD2 expression in skeletal and cardiac muscle, specifically the effect on SERCA pumps, has yet to be investigated. We obtained soleus, extensor digitorum longus (EDL), and left ventricle (LV) muscles from 6 to 7 month‐old wild‐type (WT) and Sod2 +/− female C57BL/6J mice. Ca2+‐dependent SERCA activity assays were performed to assess SERCA function. Western blotting was conducted to examine the protein content of SERCA, phospholamban, and sarcolipin; and immunoprecipitation experiments were done to assess SERCA2a‐ and SERCA1a‐specific T‐nitration. Heterozygous SOD2 deletion did not alter SERCA1a or SERCA2a expression in the soleus or LV but reduced SERCA2a in the EDL compared with WT, though this was not statistically significant. Soleus muscles from Sod2 +/− mice showed a significant reduction in SERCA’s apparent affinity for Ca2+ when compared to WT, corresponding with significantly elevated SERCA2a T‐nitration in the soleus. No effect was seen in the EDL or the LV. This is the first study to investigate the effects of SOD2 deficiency on muscle SERCA function and shows that it selectively impairs SERCA function in the soleus.

MO086THE EFFECT OF HIGH SODIUM CHLORIDE INTAKE ON CARDIOVASCULAR SYSTEM AND KIDNEYS IN SPONTANEOUSLY HYPERTENSIVE RATS

Abstract Background and Aims It is believed that high consumption of sodium chloride (NaCl) leads to the development of arterial hypertension, which result in heart remodeling, however, NaCl can probably cause direct heart damage. We aimed to evaluate the effects of high and normal NaCl containing diets on blood pressure (BP), myocardial remodeling, as well as on the level of nuclear transcription factor κB (NFκB) expression in myocardium and kidneys. Method 49 spontaneously hypertensive rats (SHR) were enrolled and subdivided into 2 groups: Group 1 (n=24) received standard diet (NaCl=0,34%); Group 2 (n=25) was on high sodium diet (NaCl=8%). In 2 months, systolic BP, myocardial and renal mass indices, morphological changes, as well as NFκB expression in heart and kidneys were assessed. Results are presented as mean ± SD. Results BP in group 2 did not change significantly (190 ± 10 mm Hg, p> 0.05) compared to group 1, yet left ventricle muscle mass indices as well as, right and left kidney mass indices were higher. Hypertrophy of cardiomyocytes (CMC) was found in group2: (area of the nucleus- 43.55 ± 17.39 μm2 (p <0.001); area of CMC-21799.31 ± 579.89 μm2 (p <0.001), compared to group 1: (area of the nucleus- 36.14 ± 4.67 μm2 (p <0.001); area of CMC-19011.13 ± 571.8 μm2 (p <0.001). Also, perivascular fibrosis was found in group2 (area of perivascular connective tissue(APCT)- 4038.96 ± 28.58 μm2 (p <0.001), compared to group1 (APCT-3718.36 ± 91.8 μm2, p <0.001). An increase in arterial wall thickness was noted in group 2 (15.71 ± 6.28 μm, p<0,001), compared to group 1 (13.51 ± 8 ,68 μm, p<0,001). The expression level of NFκB in myocardial tissue (n = 7) in group 2 was 33 times higher, and in kidney tissue (n = 5) 12 times higher than in group 1 (n = 8). Conclusion High consumption of NaCl induces NFκB activation in kidneys and myocardium, and may cause myocardial remodeling, probably via NFκB - associated signaling pathways.

Heterozygous SOD2 deletion impairs SERCA function in soleus and heart muscles from female mice

Background Sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pumps actively transport intracellular Ca2+ back into the sarcoplasmic reticulum and are the primary facilitators of muscle relaxation, restoring intracellular [Ca2+] to resting levels. Like many proteins, SERCA pumps are subject to oxidation which may affect their functional capacity. Superoxide dismutase 2 (SOD2) is a critical antioxidant enzyme localised in the mitochondrial matrix which converts superoxide radicals into less reactive H2O2. The present study sought to explore the structural and functional consequences of halved SOD2 expression, particularly to SERCA isoforms, in skeletal and cardiac muscle. Specifically, we examined whether heterozygous SOD2 deletion would result in changes in levels of SERCA tyrosine nitration and S-glutathionylation. Tyrosine nitration is known to impair SERCA function, particularly SERCA2a (slow isoform) but not SERCA1a (fast isoform). Conversely, glutathionylation of SERCA may act as an adaptive modality to preserve function during moderate oxidative stress. Methods We obtained soleus, extensor digitorum longus (EDL), and left ventricle (LV) muscles from wild-type (WT) and SOD2 heterozygote (SOD2+/-) C57BL/6J female mice (n=8 per genotype, aged 6-7 months). Ca2+-dependent SERCA activity assays were performed along with immunoprecipitation experiments to examine SERCA2a and SERCA1a tyrosine nitration and S-glutathionylation. Results Heterozygous SOD2 deletion did not alter SERCA1a or SERCA2a expression in the soleus, EDL or LV compared with WT. However, relative to WT, SOD2+/- soleus muscles showed significant impairments in SERCA function, with a reduction in SERCA's affinity for Ca2+. This corresponded well with Western blot data showing significantly elevated SERCA2a tyrosine nitration and significantly reduced S-glutathionylation in the soleus. In contrast, we observed no change in SERCA function, SERCA1a tyrosine nitration, or S-glutathionylation in the EDL. Furthermore, there were no differences in SERCA1a tyrosine nitration in the soleus, which is consistent with the notion that the SERCA1a isoform is less susceptible to nitrosative modification. Together, these results suggest that the slow SERCA isoform is more susceptible to heterozygous SOD2 deletion, and this is further supported by a significant reduction in SERCA's affinity for Ca2+ in the LV where SERCA2a is the predominant isoform. Conclusions This is the first study showing the physiological effects of halved SOD2 expression on muscle SERCA function. Our results reinforce the idea that SERCA2a is more sensitive to nitrosative modification.

Characterizing regional myofiber damage post acute myocardial infarction using global optimization

Medical imaging derived cardiac biomechanical models offer a wealth of new information to be used in diagnosis and prognosis of cardiovascular disease. A noteworthy feature of such models is the ability to predict myofiber contraction stresses during acute or chronic ischemic events. Current techniques for heterogeneous contraction models require tissue motion tracking capabilities which are neither available on all imaging modalities, nor currently used in the clinic. Proposed in this article is a proof of concept of a tissue tracking independent technique focused on shape optimization to predict the contraction stresses of in-silico left ventricle models simulating various acute myocardial infarction events. The technique involves three variables defined in the left ventricle muscle. Two of the variables represent the contraction stresses in the healthy and infarct regions while the third is a novel periinfarct variable defining a non-contracting myofiber state allowing finer classification of local myofiber damage. Results indicate that the contraction stress reconstruction errors are overall smaller than 12% when considering standard errors associated with population modelling for the new variable of interest.

Dexamethasone Does Not Inhibit Treadmill Training-Induced Angiogenesis in Myocardium: Role of MicroRNA-126 Pathway.

Dexamethasone (DEX) has important anti-inflammatory activities; however, it induces hypertension and skeletal muscle microcirculation rarefaction. Nevertheless, nothing is known about DEX outcomes on cardiac microcirculation. By contrast, exercise training prevents skeletal and cardiac microvessel loss because of microRNA expression and a better balance between their related angiogenic and apoptotic proteins in spontaneously hypertensive rats. The purpose of this study was to investigate whether DEX and/or exercise training could induce microRNA alterations leading to cardiac angiogenesis or microvascular rarefaction. Animals performed 8 weeks of exercise training and were treated with DEX (50 μg/kg per day, subcutaneously) for 14 days. Cardiovascular parameters were measured, and the left ventricle muscle was collected for analyses. DEX treatment increased arterial pressure and did not cause cardiac microcirculation rarefaction. Treadmill training prevented the DEX-induced increase in arterial pressure. In addition, training, regardless of DEX treatment, increased microRNA-126 expression, phospho-protein kinase B/protein kinase B, and endothelial nitric oxide synthase levels associated with cardiac angiogenesis. In conclusion, this study suggests, for the first time, that treadmill training induces myocardial angiogenesis because of angiogenic pathway improvement associated with an increase in microRNA-126. Furthermore, DEX, per se, did not cause capillary density alterations and did not attenuate cardiac angiogenesis induced by training.

Aging Promotes Mitochondria-Mediated Apoptosis in Rat Hearts.

Aging represents a major risk for developing cardiac disease, including heart failure. The gradual deterioration of cell quality control with aging leads to cell death, a phenomenon associated with mitochondrial dysfunction in the heart. Apoptosis is an important quality control process and a necessary phenomenon for maintaining homeostasis and normal function of the heart. However, the mechanism of mitochondria-mediated apoptosis in aged hearts remains poorly understood. Here, we used male Fischer 344 rats of various ages, representing very young (1 month), young (4 months), middle-aged (12 months), and old (20 months) rats, to determine whether mitochondria-mediated apoptotic signals and apoptosis in the left ventricle of the heart are altered notably with aging. As the rats aged, the extramyocyte space and myocyte cross-sectional area in their left ventricle muscle increased, while the number of myocytes decreased. Additionally, mitochondrion-mediated apoptotic signals and apoptosis increased remarkably during aging. Therefore, our results demonstrate that aging promotes remarkable morphological changes and increases the degree of mitochondrion-mediated apoptosis in the left ventricle of rat hearts.

ProT-α gene transfer attenuates cardiopulmonary remedying and mortality in a flow-induced pulmonary hypertension rat model

ProT is a cell survival gene, which modulates oxidative stress and transforming growth factor (TGF)-β signaling. We hypothesized that the delivery of the ProT cDNA gene in rats could protect against right heart dysfunction secondary to pulmonary hypertension (PH) induced by left-to-right shunt. A 2-hit rat model of flow-induced PH was used, and a single intravenous injection of adenoviral vectors (2 billion plaque-forming unit) carrying ProT or Luc gene was administered. The animals were euthanized 21 days after gene delivery to assess cardiopulmonary function, serum biochemistry, pulmonary artery (PA), and vasomotor reactivity. Immunohistology and immunoblotting of PA tissues were also performed. ProT transduction significantly reduced PA pressure, right ventricle muscle mass, and wall stress, thereby improving the overall survival of the treated rat. Increased production of ProT through gene therapy preserved both the smooth muscle myosin heavy chain-II and α-smooth muscle actin while counteracting the abundance of TGF-β in PA. Protein abundances of phosphorylated p47-phox, heme oxygenase-1, caspase-3, inducible nitric oxide synthase, cyclo-oxygenase 2, and monocyte chemoattractant protein-1 in PA tissues were reduced. ProT also preserved microRNA-223, thereby suppressing the abundance of PARP-1, which is independent of hypoxia-inducible factor-1α signaling. ProT gene transduction improved PA function by reducing oxidative stress, attenuating inflammation, and preserving the contractile phenotype of vascular smooth muscle cells. The modification of microRNA-223-associated downstream signaling through ProT transduction may play an important role in mitigating cardiopulmonary remodeling in flow-induced PH.

P635 Echocardiographic-fluoroscopic fusion imaging: a new technology applied in pediatric ventricular tachycardia ablation

Abstract Introduction Eleven-year-old male presented with nonsustained ventricular tachycardia presented for ablation of ventricular tachycardia located on the left lateral wall that is likely associated with anterolateral papillary muscle. Although he was asymptomatic, his atria have become dilated over time thus he was scheduled for a catheter ablation. Echocardiographic-fluoroscopic fusion imaging has shown transseptal puncture using this technology is safe and required less time in crossing the atrial septum; however, fusion imaging with 3D echocardiography overlay of left ventricular papillary muscle onto fluoroscopy has not been used in ventricular tachycardia ablations. Purpose The purpose of this clinical case was to evaluate the application of this new technology of echocardiography-fluoroscopy fusion imaging to guide left ventricular tachycardia ablation. Methods Echocardiographic-fluoroscopic fusion imaging was used for transseptal puncture and a 3D echocardiographic image of the left ventricle with anterolateral papillary muscle was overlaid onto fluoroscopy (Figure 1). The radiofrequency catheter was used to ablate the left anterolateral papillary muscle. With fused imaging, the ablation catheter was seen at the left anterolateral papillary muscle, and care was taken to prevent perforation of the lateral wall of the left ventricle. Results With fusion imaging of the left anterolateral papillary muscle overlaid onto fluoroscopy, the lateral wall of the left ventricular was also delineated. The catheter was easily visualized with fusion imaging to prevent perforation of the left ventricle while radiofrequency ablation was performed (Figure 1). Discussion 3D echocardiography provides excellent soft tissue definition of the lateral wall of the left ventricle and papillary muscle while fluoroscopy provides clear visualization of the ablation catheter. The ability of fusion imaging to overlay the 3D echocardiographic images onto fluoroscopy allowed for easy visualization of the anterolateral papillary muscle while the radiofrequency ablation was performed to avoid lateral wall perforation of the left ventricle. Future studies of echocardiographic-fluoroscopic fusion imaging should evaluate the potential to reduce procedure time and improve patient outcomes. Abstract P635 Figure.

Novel 3D heart left ventricle muscle segmentation method for PET-gated protocol and its verification

ObjectiveThe aim of this study was to propose and verify a universal method of left ventricular myocardium segmentation, able to operate on heart gated PET data with different sizes, shapes and uptake distributions. The proposed method can be classified as active model method and is based on the BEAS (B-spline Explicit Active Surface) algorithm published by Barbosa et al. The method was implemented within the Pmod PCARD software package. Method verification by comparison with reference software and phantom data is also presented in the paper.MethodsThe proposed method extends the BEAS model by defining mechanical features of the model: tensile strength and bending resistance. Formulas describing model internal energy increase during its stretching and bending are proposed. The segmentation model was applied to the data of 60 patients, who had undergone cardiac gated PET scanning. QGS by Cedars-Sinai and ECTb by Emory University Medical Centre served as reference software for comparing ventricular volumes. The method was also verified using data of left ventricular phantoms of known volume.ResultsThe results of the proposed method are well correlated with the results of QGS (slope: 0.841, intercept: 0.944 ml, R2: 0.867) and ECTb (slope: 0.830, intercept: 2.109 ml, R2: 0.845). The volumes calculated by the proposed method were very close to the true cavity volumes of two different phantoms.ConclusionsThe analysis of gated PET data by the proposed method results in volume measurements comparable to established methods. Phantom experiments demonstrate that the volume values correspond to the physical ones.

Improving image quality with model-based iterative reconstruction algorithm for chest CT in children with reduced contrast concentration.

To evaluate model-based iterative reconstruction (MBIR) in improving the image quality of chest CT in children with reduced concentration contrast medium (CM). Fifty-six children (median age of 4years) who received low-dose enhanced chest CT were enrolled as the study group and compared with the control group of 56 children. Both groups used the automatic tube current modulation to achieve age-based noise index values of 11-15HU. The study group used 100kVp and reduced CM concentration of 270mgI/ml, and the images in this group were reconstructed with 50% adaptive statistical iterative reconstruction (ASIR) and MBIR. The control group used 120kV and standard CM of 320mgI/ml, and the images in this group were reconstructed with ASIR only. Subjective image quality and objective image quality of the three image sets were evaluated. The subjective quality included overall image noise, enhancement degree, lesion (including mediastinum mass, pulmonary space-occupying lesions, and parenchymal infiltrative lesions) conspicuity, and beam-hardening artifacts. The objective quality included the measurement of noise in the left ventricle and back muscle to calculate signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of ventricle. There was no difference in radiation dose between the study (CTDIvol of 1.79 ± 1.45mGy) and control (1.68 ± 0.92mGy) groups (p = 0.65). However, the study group used 19.7% lower CM dose than the control group (5.84 ± 2.69 vs. 7.27 ± 3.80gI), and the enhancement in all images met the diagnostic requirements. MBIR reduced image noise by 58.6% and increased SNR and CNR by 143.6% and 165.7%, respectively, compared to ASIR images in the control group. The two ASIR image sets had similar image quality. MBIR improved the image quality of low-radiation-dose chest CT in children at 19.3% reduced CM dose.

Histopathological changes of right ventricle outflow tract myocardium in relation to age in tetralogy of Fallot and its relation to clinical outcome

BackgroundRight ventricle outflow tract myocardium in tetralogy of Fallot reflects the effect of hemodynamic stresses on right ventricle muscle and correlates with clinical right ventricle dysfunction. It may be a useful adjunct in determining the time for intracardiac repair and predicting the clinical outcome. MethodsSeptal and parietal bands of infundibular septum and obstructing muscle bands were excised in 48 patients undergoing intracardiac repair for tetralogy of Fallot. Microscopic study of histopathological changes in resected muscle bands was done. Post operative 2D echocardiography and tissue doppler imaging were done at the end of first and third month evaluating the right ventricular function. ResultsModerate myocardial fibrosis was seen in 42.9% (12/28) patients with age >5 years compared to 37.5% (6/16) patients with age between 1-5 years and 0% patients with age < 1 year (P >0.05). Right ventricular dysfunction was seen in 41.9% (18/43) patients who had no myocardial ischemia compared to 60% (3/5) patients with myocardial ischemia. Right ventricular dysfunction was noted in 13.33% (4/30) patients having mild myocardial fibrosis compared to 33.33% (6/18) patients with moderate myocardial fibrosis (P >0.05). Early postoperative right ventricular dysfunction was seen in more number of patients with increasing age as calculated by fractional area changes and Tei index. ConclusionsMyocardial fibrosis was seen in more number of patients as age progresses. Early postoperative right ventricular dysfunction was more frequent in patients with higher grade of myocardial fibrosis and higher age group.

Glucose Metabolism as a Pre-clinical Biomarker for the Golden Retriever Model of Duchenne Muscular Dystrophy

PurposeMetabolic dysfunction in Duchenne muscular dystrophy (DMD) is characterized by reduced glycolytic and oxidative enzymes, decreased and abnormal mitochondria, decreased ATP, and increased oxidative stress. We analyzed glucose metabolism as a potential disease biomarker in the genetically homologous golden retriever muscular dystrophy (GRMD) dog with molecular, biochemical, and in vivo imaging.ProceduresPelvic limb skeletal muscle and left ventricle tissue from the heart were analyzed by mRNA profiling, qPCR, western blotting, and immunofluorescence microscopy for the primary glucose transporter (GLUT4). Physiologic glucose handling was measured by fasting glucose tolerance test (GTT), insulin levels, and skeletal and cardiac positron emission tomography/X-ray computed tomography (PET/CT) using the glucose analog 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG).ResultsMRNA profiles showed decreased GLUT4 in the cranial sartorius (CS), vastus lateralis (VL), and long digital extensor (LDE) of GRMD vs. normal dogs. QPCR confirmed GLUT4 downregulation but increased hexokinase-1. GLUT4 protein levels were not different in the CS, VL, or left ventricle but increased in the LDE of GRMD vs. normal. Microscopy revealed diffuse membrane expression of GLUT4 in GRMD skeletal but not cardiac muscle. GTT showed higher basal glucose and insulin in GRMD but rapid tissue glucose uptake at 5 min post-dextrose injection in GRMD vs. normal/carrier dogs. PET/ CT with [18F]FDG and simultaneous insulin stimulation showed a significant increase (p = 0.03) in mean standard uptake values (SUV) in GRMD skeletal muscle but not pelvic fat at 5 min post-[18F]FDG /insulin injection. Conversely, mean cardiac SUV was lower in GRMD than carrier/normal (p < 0.01).ConclusionsAltered glucose metabolism in skeletal and cardiac muscle of GRMD dogs can be monitored with molecular, biochemical, and in vivo imaging studies and potentially utilized as a biomarker for disease progression and therapeutic response.

OS 25-06 CENTRAL ANGIOTENSIN II ACCELERATES BRAIN INJURY AND SARCOPENIA ASSOCIATED WITH OXIDATIVE STRESS IN A MOUSE MODEL OF ALZHEMIER'S DISEASE.

Objective: Increasing evidences suggest that patients with Alzheimer's disease (AD) show not only cognitive impairment but also physical disorder including cardiac dysfunction and sarcopenia. In this study, we investigated whether central angiotensin II, inducer of oxidative stress, led to the organ dysfunction in a mouse model of AD. Design and Method: 5XFAD which is an animal model of AD and C57BL/6 (WT) were each assigned to 1) normal saline and 2) angiotensin II (20 mg/kg/h) groups. Those solutions were infused intracerebroventricularly for 28 days. The changes of blood pressure, body weight, food and water intake, urinary volume, rotarod test, and watermaze test were monitored at appropriate time point. At 28 days after the start of the intracerebral infusion, weights of their brain, left ventricle, and gastrocnemius muscle were measured and histological evaluations which were related to oxidative stress and amyloid β protein (Aβ) deposition were conducted. Results: Angiotensin II increased blood pressure and decreased body weight, whereas food intake was not changed among the groups. Although angiotensin II deteriorated motor function detected by rotarod test in 5XFAD, it showed similar effect in cognitive impairment both WT and 5XFAD without brain atrophy. On the other hand, histological evaluation revealed that angiotensin II did not increase hippocampal superoxide and macrophage expressions in WT, but upregulated them in 5XFAD without loading of Ab deposition. In addition, angiotensin II induced cardiac hypertrophy and cardiomyocyte fibrosis in WT, while atrophy and upregulated macrophage expression by angiotensin II in gastrocnemius muscle were seen in 5XFAD. Conclusions: We suggest that central activation of RAS might play important roles in progression of brain injury and sarcopenia of AD patients.

MITRAL APPARATUS DYNAMIC CHANGES AFTER ACUTE MYOCARDIAL INFARCTION: COMPREHENSIVE QUANTITATIVE 3D ECHOCARDIOGRAPHIC ASSESSMENT

The mitral apparatus is a dynamic structure comprised of left ventricle (LV), mitral leaflet, annulus and papillary muscle that changes shape through the cardiac cycle. The impact of myocardial infarction (MI) on 3D dynamics of the mitral apparatus is unknown. We studied the relationship between LV