Ventricular Fractional Shortening Research Articles

Role of hesperetin intervention on cardiac function and ventricular remodeling after myocardial infarction

Objective To explore the effect of hesperidin on cardiac function and ventricular remodeling following myocardial infarction (MI) in mice. Methods Ligation of left anterior descending (LAD) was operated to establish MI model. Forty-two C57BL/6 mice were randomly(random number) divided into control and MI group; and 24 h after LAD ligation, mice in MI group were further divided into MI control and hesperetin group. Eight weeks later, cardiac function and structure changes were determined by the methods of hemodynamic measurement and echocardiography. HE staining was used to measure cross-sectional area (CSA) of atrial myocytes, and PSR staining was applied for observe collagen deposition and calculation of collagen volume fraction (CVF). Real-time PCR was used to detect the mRNA expressions of cardiac hypertrophy markers (ANP, BNP and β-MHC) and cardiac fibrosis markers (Collagen Ⅰ, Collagen Ⅲ and CTGF). The contents of superoxide anion and hydroxy radical were detected by colorimetric method. Results Compared with control group, left ventricular posterior wall thickness (LVPWT) and inter-ventricular septum thickness (IVST) were increased to be thicker, left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) were significantly lower, and ±dp/dtmax was remarkably reduced in MI control group (P<0.05). Compared with MI control group, hesperetin could increase LVFS[(29.48±3.87)% vs. (20.69±3.99) %], LVEF [(46.40±1.68)% vs. (30.51±1.17) %] and ±dp/dtmax [(3 344.33±269.57)mmHg/S vs. (2 205.19±224.17)mmHg/S; (-2 250.40±218.35)mmHg/S vs. (-1 566.91±217.37) mmHg/S]; but could reduce LVPWT [(2.29±0.05)mm vs. (2.85±0.10) mm] and IVST [(1.44±0.09)mm vs.(1.89±0.06)mm]. Compared with control group, CSA and CVF were significantly increased in MI control mice. However, hesperetin could reduce CSA and CVF. Compared with control group, the mRNA expressions of cardiac hypertrophy and cardiac fibrosis markers were significantly increased in MI control mice; but hesperetin could significantly inhibit the mRNA expressions of cardiac hypertrophy and cardiac fibrosis markers. Additionally, hesperetin could significantly reduce the contents of superoxide anion and hydroxy radical. Conclusion Hesperetin intervention can inhibit ventricular structure change, and improve hemodynamics and cardiac function after acute myocardial infarction via inhibiting the production of reactive oxygen species (ROS). Key words: Hesperetin; Myocardial infarction; Cardiac function; Ventricular remodeling; Reactive oxygen species; Mice

Suppression of microRNA-135b-5p protects against myocardial ischemia/reperfusion injury by activating JAK2/STAT3 signaling pathway in mice during sevoflurane anesthesia.

The study aims to explore the effects of miR-135b-5p on myocardial ischemia/reperfusion (I/R) injuries by regulating Janus protein tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway by mediating inhalation anesthesia with sevoflurane. A sum of 120 healthy Wistar male mice was assigned into six groups. Left ventricular ejection fraction (LVEF) and left ventricular shortening fraction (LVSF) were detected. Cardiomyocyte apoptosis was determined by terminal dexynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay. MiR-135b-5p expression, mRNA and protein expression of p-STAT3, p-JAK2, STAT3, JAK2, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein B (Bax) were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. Target relationship between miR-135b-5p and JAK2 was confirmed by dual-luciferase reporter assay. The other five groups exhibited increased cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, mRNA expression of JAK2 and STAT3, and protein expression of p-STAT3 and p-JAK2 compared with the sham group, but showed decreased LVEF, LVFS, and Bcl-2 expression. Compared with the model and AG490 + Sevo groups, the Sevo, inhibitor + Sevo and inhibitor + AG490 + Sevo groups displayed reduced cardiomyocyte necrosis, apoptosis, miR-135b-5p and Bax expression, but displayed elevated mRNA expression of JAK2 and STAT3, protein expression of p-STAT3 and p-JAK2, LVEF, LVFS and Bcl-2 expression. Compared with the Sevo and inhibitor + AG490 + Sevo groups, the AG490 + Sevo group showed decreased LVEF, LVFS, Bcl-2 expression, mRNA expressions of JAK2 and STAT3, and protein expressions of p-STAT3 and p-JAK2, but increased cardiomyocyte necrosis, apoptosis, and Bax expressions. MiR-135b-5p negatively targetted JAK2. Inhibition of miR-135b-5p can protect against myocardial I/R injury by activating JAK2/STAT3 signaling pathway through mediation of inhalation anesthesia with sevoflurane.

Fetal Heart Function by Tricuspid Annular Plane Systolic Excursion and Ventricular Shortening Fraction Using STIC M-Mode: Reference Ranges and Validation.

Objective To determine the reference values for fetal tricuspid annular plane systolic excursion (f-TAPSE) and fetal ventricular shortening fraction (f-VSF) using spatiotemporal image correlation (STIC) with M-mode, and validate these curves in fetuses of pregnant women with preexisting diabetes mellitus (DM) and with intrauterine growth restriction (IUGR). Study Design Crosssectional study assessed 300 fetal cardiac volumes of normal pregnancies between 20 and 33 + 6 weeks of gestation. For the construction of the reference curves, we used a polynomial regression model adjusted with the coefficient of determination (R2). For the calculation of reproducibility, the concordance correlation coefficient (CCC) was used. Results f-TAPSE value correlated with gestational age (GA, R2 = 0.46), whereas fetal right ventricular shortening fraction (f-RVSF, R2 = 0.02) and fetal left ventricular shortening fraction (f-LVSF, R2 = 0.005) did not vary with GA. Fetuses of pregnant women with preexisting DM (30) had lower values of f-RVSF (p = 0.028), f-LVSF (p = 0.001), and f-TAPSE (p = 0.009) than normal fetuses. The f-TAPSE values were lower (p = 0.005) in IUGR group (17). The f-TASPSE values showed adequate reliability as well as good intra and interobserver concordance (CCC = 0.95 and 0.79, respectively). Conclusion The reference ranges for f-TAPSE, f-RVSF, and f-LVSF using the STIC M-mode were established and had good reproducibility for f-TAPSE measurements.

Xinfuli Granule improves post-myocardial infarction ventricular remodeling and myocardial fibrosis in rats by regulating TGF-β/Smads signaling pathway.

BackgroundRecent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinese medicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG on ventricular reconstruction in rats with acute myocardial infarction (AMI).MethodsSprague-Dawley rats were subjected to left anterior descending branch ligation. The rats that survived 24 h were randomly assigned to five groups: medium-dose of XG group (MI+XGM), high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM). Fourteen rats underwent identical surgical procedures without artery ligation, serving as sham controls. At 28 days, left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW) were calculated; left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), left ventricular internal diameter at systole (LVIDS) were measured by ultrasound; HE staining, Masson staining, and Sirius red staining were used to assess the myocardial pathological and physiological changes as well as myocardial fibrosis area and non-infarct zone I/III collagen ratio. Expression of Smad3 were detected and analyzed by Western blot, immunohistochemistry and immunofluorescence. P-Smad3, Smad2 and Smad7 in the TGF-β/Smads signaling pathway were also analyzed by Western blot.ResultsThe LVIDS (P < 0.01), HW/BW (P < 0.05), type I/III collagen ratio (P < 0.01) and myocardial collagen (P < 0.01) decreased significantly while the LVW/BW, LVFS (P < 0.05) increased significantly in MI+XGM group as compared with those in other groups. The expression of key signal molecules of the TGF-β/Smads signaling pathway, including Smad3, P-Smad3 and Smad2 protein were decreased, while the expression of Smad7 increased in both XG and carvedilol treatment groups as compared to those of the MI group (all P < 0.01). Immunohistochemistry and immunofluorescence further confirmed the down-regulated Smad3 expression.ConclusionXG can improve ventricular reconstruction and inhibit myocardial fibrosis in rats with AMI by regulating TGF-β/Smads signaling pathway.

Would healing was improved in mice after myocardial infarction by nature naphthoquinone shikonin

Wound healing has an important impact on ventricular remodeling and functional recovery after myocardial infarction (MI). Nature naphthoquinone shikonin has been shown to promote wound healing by reducing reactive oxygen species and inflammation. However, it is still unknown whether shikonin can increase wound healing in infarcted hearts. C57BL6 mice were subjected to MI surgery. Infarcted mice were treated with shikonin by oral gavage, 25 mg/kg once a day for four weeks, or the equal volume of vehicle as controls. At the end of the experiments, echocardiography was performed. Echo study showed that shikonin improved left ventricular fractional shortening and ejection fraction, and that it decreased left ventricular dilation and increased infarcted wall thickening. Moreover, the ratio of heart weight to body weight was decreased in shikonin‐treated group, compared with vehicle group. Masson's trichrome staining demonstrated fibrosis was inhibited in non‐infarcted regions in shikonin‐treated group. Taken together, shikonin promoted wound healing and improved left ventricular functional recovery in infarcted hearts.

Effects of renal denervation on cardiac oxidative stress and local activity of the sympathetic nervous system and renin-angiotensin system in acute myocardial infracted dogs

BackgroundThis study sought to evaluate the therapeutic effects of renal denervation (RDN) on acute myocardial infarction (MI) in canines and explore its possible mechanisms of action.MethodsEighteen healthy mongrel dogs were randomly assigned to either the control group, the MI group or the MI + RDN group. To assess cardiac function, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and fraction shortening (FS) were recorded. Additionally, haemodynamic parameters such as left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and heart rate (HR) were measured. Cardiac oxidative stress levels were evaluated based on the expression of p47phox mRNA, malondialdehyde (MDA), anti-superoxide anion free radical (ASAFR) and activity of superoxide dismutase (SOD). To measure the local activity of the sympathetic nervous system (SNS) and renin-angiotensin system (RAS), the levels of tyrosine hydroxylase (TH), angiotensin II (AngII), angiotensin-converting enzyme 2 (ACE2), angiotensin (1–7) [Ang(1–7)] and Mas receptor (MasR) in myocardial tissues were recorded. The expression of TH in renal tissue and serum creatinine were used to assess the effectiveness of the RDN procedure and renal function, respectively.ResultsWe found that MI deteriorated heart function and activated cardiac oxidative stress and the local neurohumoral system, while RDN partially reversed these changes. Compared with the control group, parameters including LVEDD, LVESD, LVEDP and the levels of ASAFR, MDA, p47phox,ACE2, Ang(1–7), MasR, AngII and TH-positive nerves were increased (all P < 0.05) in myocardial infracted dogs; meanwhile, LVEF, FS, LVSP and SOD expression were decreased (all P < 0.05). However, after RDN therapy, these changes were significantly improved (P < 0.05), except that there were no significant differences observed in FS or LVSP between the two groups (P = 0.092 and 0.931, respectively). Importantly, the expression of TH, AngII and Ang(1–7) was positively correlated with MDA and negatively correlated with SOD. Between-group comparisons demonstrated no differences in serum creatinine (P = 0.706).ConclusionsRDN attenuated cardiac remodelling and improved heart function by decreasing the level of cardiac oxidative stress and the local activity of the SNS and RAS in cardiac tissues. Additionally, the safety of the RDN procedure was established, as no significant decrease in LVSP or rise in serum creatinine was observed in our study.

Preventive Physical Training Partially Preserves Heart Function and Improves Cardiac Antioxidant Responses in Rats After Myocardial Infarction Preventive Physical Training and Myocardial Infarction in Rats

In acute myocardial infarction (AMI), reactive oxygen species may cause irreversible damage to the heart tissue. Physical training is capable of enhancing antioxidant capacity, acting as a cardioprotective factor. We assessed the preventive effects of physical training on the antioxidant and functional responses of the heart of Wistar Kyoto rats after AMI. Wistar Kyoto rats (n = 12) were allocated to sedentary (SED) or trained (EXE-aerobic training on a treadmill) groups. Echocardiographic exams were performed 48 hr before and 48 hr after the induction of AMI. Superoxide dismutase (SOD) and catalase (CAT) activities, and total glutathione (GSH) were measured in vitro in the heart tissue. After AMI, the EXE group showed higher left ventricular shortening fraction (29%; p = .004), higher cardiac output (37%; p = .032) and reduced myocardial infarction size (16%; p = .007) than SED. The EXE group showed a higher nonenzymatic antioxidant capacity (GSH, 23%; p = .004), but the SOD and CAT activities were higher in SED (23% SOD; p = .021 and 20% CAT; p = .016). In addition, the SOD activity was positively correlated with myocardial infarction size and inversely correlated with cardiac output. Physical training partially preserved cardiac function and increased intracellular antioxidant response in cardiac tissue of animals after AMI.

Echocardiographic study of left ventricular structure and function in Nigerian patients with chronic liver disease

Background: The concept of cirrhotic cardiomyopathy includes impaired cardiac contractility, decreased beta-adrenergic receptor function, abnormal beta-adrenergic postreceptor function, defective excitation-contraction coupling, and cardiac conduction abnormalities. This study was aimed to assess the cardiac structure and function in adult Nigerians with chronic liver disease (CLD). Methods: This was a cross-sectional descriptive study of consecutive patients with CLD without any known cardiac disease attending the Liver Clinic of the Medical Out-patient Department of the University College Hospital. Apparently, normal individuals with comparable age and sex distribution were recruited as controls. The subjects and controls underwent two-dimensional, M-mode and Doppler echocardiographic studies to determine the cardiac structure in relation to both systolic and diastolic cardiac functions. Results: A total of 46 subjects and 50 normal controls were recruited. There was no difference in the blood pressure parameters of the two groups. The septal wall thickness was statistically higher in control, but this difference was lost when adjusted for body mass index. On the other hand, the adjusted left atrial diameter and aortic root dimension were statistically larger in the subjects than the controls. There was no difference in the left ventricular (LV) fractional shortening or ejection fraction, relative wall thickness, and deceleration time of the E-wave. Conclusions: We demonstrated an increase in cardiac index at rest in the subjects, but there was no significant difference in the LV diastolic or systolic dysfunction using traditional methods. Studies using newer modalities of the assessment of cardiac structure and function are needed in our environment.

Effects of renal denervation on left ventricular remodeling and cardiac oxidative stress after myocardial infarction in canine

Objective To investigate the effects of renal denervation (RDN) on left ventricular remodeling and cardiac oxidative stress due to myocardial infarction (MI) in canine. Methods Anterior myocardial infarction was produced by gelatin sponge embolization of the left anterior descending artery. Eighteen canines were randomly divided into three groups. Sham group (renal arteriography performed a week after coronary angiograph, n=6), MI group (renal arteriography performed a week after MI, n=6), and RDN group (RDN performed a week after MI, n=6). Four weeks post-MI, left ventricular function was measured by hemodynamics. Echocardiography examination was administered to identify left ventricular end-diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD), fraction shortening (FS), and left ventricular ejection fraction (LVEF). Anti-superoxide anion free radical (ASAFR) activity was detected by colorimetry. Thiobarbituric acid method was used to measure the concentration of malonaldehyde (MDA). Results Compared to Sham group, the LVEF, FS and left ventricular systolic pressure (LVSP) in MI group and RDN group were decreased obviously (all P 0.05). There were no significant difference in heart rate (HR) among three groups (P>0.05). Although the levels of MDA, ASAFR, and p47phox mRNA were higher in MI group and RDN group, compared to the Sham group (all P<0.05), they were all significantly decreased in RDN group compared to the MI group (all P<0.05). Conclusions RDN was able to improve heart function and myocardial remodeling and inhibit cardiac oxidative stress. Key words: Sympathectomy; Kidney/IR; Myocardial infarction/CO/SU; Ventricular remodeling; Oxidative stress; Myocardium/PA

Xinfuli improves cardiac function, histopathological changes and attenuate cardiomyocyte apoptosis in rats with doxorubicin-induced cardiotoxicity.

BackgroundXinfuli Granule (XG), a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with doxorubicin-induced cardiotoxicity.MethodsSprague–Dawley rats were treated with intraperitoneal injection of Doxorubicin (DOX, 2.5 mg/kg per week) for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline (control group) or different dosage of XG (0.675 g/kg per day, 1.35 g/kg per day, and 2.7g/kg per day, respectively) for six weeks. Transthoracic echocardiography was performed to evaluate the left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) before and after the XG treatment and histopathologic changes were also examined. Myocardial cell apoptosis was detected by TUNEL staining. The expression of related genes and proteins were analyzed using immunohistochemical staining.ResultsCompared to those in the control group, rats in XG treated groups showed significantly improved cardiac function and milder cardiac histopathological changes, lower cardiomyocyte apoptosis index, higher expression of Bcl-2 and lower expression of Bax.ConclusionsAdministration of XG improves cardiac function and histopathological changes in rats with doxorubicin-induced cardiotoxicity. These effects are associated with inhibition of cardiomyocyte apoptosis, perhaps via regulation of Bcl-2 and Bax protein expression.

Cardiovascular Profile of Propranolol after Multiple Dosing in Infantile Hemangioma

Propranolol is becoming the treatment of choice for complicated infantile hemangioma. We report here data on peripheral blood flow, O₂-saturation, electrocardiographic PR-interval, left ventricular function, blood pressure and heart rate that were assessed before and during treatment for ≥4 weeks with propranolol 2 mg/kg of body weight daily in 67 infants <12 months of age in normal sinus rhythm and with structurally normal hearts. Management with propranolol was well tolerated in all and did not modify peripheral blood flow, O₂-saturation, electrocardiographic PR-interval and left ventricular fractional shortening or ejection fraction. Absolute blood pressure levels were similar without and with propranolol. However, age-adjusted centile levels for both systolic and diastolic levels were significantly lower while on propranolol. The heart rate was significantly lower both when expressed as absolute value and when expressed as age-adjusted centile on treatment with propranolol. In conclusion, propranolol 2 mg/kg of body weight daily causes a statistically though not clinically relevant decrease in blood pressure and heart rate in cardially healthy infants affected by infantile hemangioma. Temporary discontinuation during acute febrile illnesses and during diarrheal diseases should be considered to prevent excessive hypotension.

State of the Art Reviews: Effects of Obesity on Cardiac Function in Adolescent Females

Cardiomyopathy of obesity in adults is characterized by augmented cardiac output but diminished myocardial performance. This study of healthy adolescent females (mean age 13.7 ± 1.9 years) with a wide range of body fat content was designed to assess evidence of cardiomyopathy in obese youth. Thirteen adolescent females with morbid obesity (body mass index >40 kg m—2) underwent evaluation of resting cardiac size and function as well as cardiac functional reserve during a maximal cycle exercise test. Data were combined with that previously published from this laboratory of nonobese and moderately obese teenage girls and then correlated with body mass index as a marker of obesity. At rest, heart size, stroke volume, and cardiac output were directly related to degree of obesity, whereas a negative correlation was observed between ventricular shortening fraction and body mass index (r = -0.47, P < .01). However, no impairment was observed in cardiac functional reserve with exercise. Maximal cardiac output and ...

Cause analysis of young patients with chest pain and negative results of coronary angiography

Objective To reduce the incidence of sudden cardiac death in young individuals with chest pain suspected to be acute coronary syndrome (ACS) and negative results of angiography, and so explored the causes of it. Methods A total of 134 young patients with suspected ACS admitted in PLA general hospital from January 2014 to December 2014 , were checked by coronary angiography. Comparisons of gender, professions, BMI, biochemical variables including glycohemoglobin (HBA1c), triglyceride (TG), C-reactive protein (CRP), troponin T (cTnT), high-density lipoprotein (HDL), brain natriuretic diuresis peptide (BNP)) and cardiac function including interventricular septum thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume and left ventricular systolic volume, stroke volume, ejection fraction and shortening fraction of left ventricle, E value, A value, E/A value among coronary angiography negative group (n=64), coronary angiography positive group (n=70) and healthy subjects group (n=77) . Quantitative variables were presented as means ± standard deviations, categorical data were presented as absolute values and percentages compared using t-test. One-way ANOVA was used to analyze variance between groups. Results The causes of negative group were found to be coronary atherosclerosis (90.6%), cardiac neurosis (4.7%), cardiomyopathy (1.6%), cardiac syndrome X (1.6%), and other 3.2%. There were 81.1% male and 58.9% officer of civil service management and business service personnel in negative group. The young patients in negative group had higher levels of BMI (P=0.000), total cholesterol (TC) (P=0.000), hypersensitive C-reactive protein (CRP) (P=0.003), cardiac troponin T (cTnT) (P=0.009) and lower high density lipoprotein (HDL) (P=0.000) compared with healthy subjects group. There was no significant difference in level of brain natriuretic peptide (BNP) between negative group and healthy subjects group (P=0.128). There were higher levels of left ventricular ejection fraction (LVEF) (P=0.000) and fractional shortening (FS) (P=0.000), and lower left ventricular end systolic volume (P=0.006) in negative group compared with positive group. Conclusions Coronary atherosclerosis is the major cause of young patients with chest pain suspected acute coronary syndrome (ACS) and with negative results of coronary angiography. Male, high stress occupation, a sedentary job, obesity, hyperglycemia and dyslipidemia are risk factors. Early diagnosis and prevention strategy are mandatory in these specific young individuals. Key words: Young people; Acute coronary syndrome; Sudden cardiac death; Chest pain; Causes; Coronary angiography negative; Biochemical indicators; Gender; Profession; Heart function

Effects of danshensu on cardiac function and myocardial fibrosis in pressure-overloaded mice

Objective To observe the effect of Danshensu (DSS) on cardiac function and myocardial fibrosis in pressure-overloaded mice. Methods C57BL/6 male mice were randomly divided into four groups: Sham-Saline, Sham-DSS, TAC-Saline and TAC-DSS. Mice ventricular remodeling model were established by transverse aortic constriction (TAC) operation. One week later, the mice were fed with DSS or Saline for 7 weeks. After echocardiographic evaluation, cardiomyocyte cross-sectional area and myocardial fibrosis were determined by hematoxylin and eosin (HE) and Masson staining, respectively. Western blotting analysis was performed to detect the expression of transforming growth factor-β1 (TGF-β1)/Smad signaling pathway related proteins. Results Compared with Sham-Saline group, the left ventricular ejection fraction and fraction shortening in TAC-Saline group were reduced [(48.19±1.11)% vs. (80.78±1.30)%; (24.36±0.63)% vs. (42.87±1.09)%, P<0.05], which could be improved by DSS [(57.35±1.09)% and (29.88±0.68)%, respectively, P<0.05]. HE staining indicated an enlargement in cardiomyocyte cross-sectional area after TAC [(379±25) μm2 vs. (192±12) μm2,P<0.05], which could be ameliorated by DSS [(264±18) μm2,P<0.05]. Masson staining demonstrated that the degree of myocardial fibrosis was increased following TAC [(11.34±1.43)% vs. (2.18±0.14)%, P<0.05], which could be mitigated by DSS intervention[(5.26±1.17)%, P<0.05]. In addition to a reduction in Smad7 protein content, an increase in the protein level of p-Smad2, p-Smad3 and TGF-β1 were also observed in TAC-Saline group compared to Sham-Saline group (P<0.05); compared with TAC-Saline group, TAC-DSS group showed a reduced expression of p-Smad2, p-Smad3 and TGF-β1 and an increased expression of Smad7 (P<0.05). Conclusion DSS may ameliorate myocardial fibrosis via TGF-β1/Smad signaling pathway, thus improving the cardiac function and ventricular remodeling after pressure overload. Key words: Danshensu; Transverse aortic constriction; transforming growth factor-β1/Smad; Myocardial fibrosis

Effect of stromal cell-derived factor-1 on myocardial apoptosis and cardiac function recovery in rats with acute myocardial infarction

The aim of the study was to investigate the effect of stromal cell-derived factor-1 (SDF-1) on myocardial apoptosis and cardiac function recovery in rats with acute myocardial infarction (AMI) and the mechanism of the Toll-like receptor (TLR)-4/nuclear factor-κB (NF-κB) signaling pathway. A total of 64 healthy male F344 rats were randomly divided into the sham operation, model, SDF-1 intervention and SDF-1 antibody groups, with 16 rats in each group. The method of Olivette was used to establish the AMI model by ligation of the left anterior descending artery. Day 1 after establishing the animal model, the rats in the SDF-1 intervention group were injected with 10 µl recombinant SDF-1 (400 ng/ml) in five regions including the myocardial infarction area and the four surrounding areas. The rats in the model group were injected with 10 µl normal saline including the myocardial infarction area and the four surrounding areas, and those in the SDF-1 antibody group were injected with 1 ml SDF-1 antibody (2 µg/ml). Four rats were sacrificed after 1, 3, 7 and 14 days after the intervention, and the analysis was carried out. TUNEL in situ labeled apoptotic cells were used for cell counting, and immunohistochemical staining was performed to measure vascular density. The animal echocardiographic measurement was for the left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), left ventricular fractional shortening (FS) and ejection fraction (EF) values. The results showed that the number of apoptotic cells in the SDF-1 treatment group was significantly lower than those in the other groups at each time-point. The vessel densities in the 3–14 days were significantly greater than those in other groups. At each time-point, the LVEDd and LVESd values were smaller compared with the model group, but greater than the sham operation group and decreased over time. FS and EF values were higher than those in the model group at each time-point, but less than those of the sham operation group and increased over time. The expression levels of TLR-4 and NF-κB at each time-point were significantly higher than those of the remaining groups (p<0.05). In conclusion, SDF-1 is capable of decreasing the apoptosis of cardiac muscle cells in AMI, promoting angiogenesis and improving cardiac function, which may be associated with the activation of the TLR-4/NF-κB signaling pathway.

Polydatin post-treatment alleviates myocardial ischaemia/reperfusion injury by promoting autophagic flux.

Polydatin (PD), a resveratrol (RES) glycoside, has a stronger antioxidative effect than RES. It is known that RES is an autophagic enhancer and exerts a cardioprotective effect against ischaemia/reperfusion (I/R) injury. However, the effect of PD post-treatment on myocardial I/R injury remains unclear. In the present study, we investigated the influences of PD post-treatment on myocardial I/R injury and autophagy. C57BL/6 mice underwent left coronary artery (LCA) occlusion and cultured neonatal rat cardiomyocytes (NRCs) subjected to hypoxia were treated with vehicle or PD during reperfusion or re-oxygenation. We noted that PD enhanced autophagy and decreased apoptosis during I/R or hypoxia/reoxygenation (H/R), and this effect was antagonized by co-treatment with adenovirus carrying short hairpin RNA for Beclin 1 and 3-methyladenine (3-MA), an autophagic inhibitor. Compared with vehicle-treated mice, PD-treated mice had a significantly smaller myocardial infarct size (IS) and a higher left ventricular fractional shortening (LVFS) and ejection fraction (EF), whereas these effects were partly reversed by 3-MA. Furthermore, in the PD-treated NRCs, tandem fluorescent mRFP-GFP-LC3 assay showed abundant clearance of autophagosomes with an enhanced autophagic flux, and co-treatment with Bafilomycin A1 (Baf), a lysosomal inhibitor, indicated that PD promoted the degradation of autolysosome. In addition, PD post-treatment reduced mitochondrial membrane potential and cellular reactive oxygen species (ROS) production in NRCs, and these effects were partially blocked by Baf. These findings indicate that PD post-treatment limits myocardial I/R injury by promoting autophagic flux to clear damaged mitochondria to reduce ROS and cell death.

S100A8 and S100A9 Are Associated with Doxorubicin-Induced Cardiotoxicity in the Heart of Diabetic Mice.

Cardiomyopathy is a clinical problem that occurs in the hearts of type 2 diabetic patients as well as cancer patients undergoing doxorubicin chemotherapy. The number of diabetic cancer patients is increasing but surprisingly the cardiac damaging effects of doxorubicin, a commonly used chemotherapeutic drug, on diabetic hearts have not been well-examined. As the signaling mechanisms of the doxorubicin-induced cardiomyopathy in type 2 diabetic heart are largely unknown, this study examined the molecular signaling pathways that are responsible for the doxorubicin-induced cardiotoxicity in type 2 diabetic hearts. Male 14- to 18-week-old db/db mice were used as the type 2 diabetic model, and age-matched non-diabetic db/+ mice served as controls. The db/+ non-diabetic and db/db diabetic mice were randomly assigned to the following groups: db/+CON, db/+DOX-5d, db/+DOX-7d, db/dbCON, db/dbDOX-5d, and db/dbDOX-7d. Mice assigned to doxorubicin (DOX) group were exposed to an intraperitoneal (i.p.) injection of DOX at a dose of 15 mg/kg to induce cardiomyopathy. Mice in control (CON) groups were i.p. injected with the same volume of saline instead of DOX. Mice were euthanized by overdose of ketamine and xylazine 5 or 7 days after the DOX injection. Microarray analysis was adopted to examine the changes of the whole transcriptional profile in response to doxorubicin exposure in diabetic hearts. Ventricular fractional shortening was examined as an indicator of cardiac function by transthoracic echocardiography. The presence of diabetic cardiomyopathy in db/db mice was evident by the reduction of fractional shortening. There was a further impairment of cardiac contractile function 7 days after the DOX administration in db/db diabetic mice. According to our microarray analysis, we identified a panel of regulatory genes associated with cardiac remodeling, inflammatory response, oxidative stress, and metabolism in the DOX-induced cardiac injury in diabetic heart. The microarray results of selected genes were confirmed by real time PCR. Notably, S100A8 and S100A9 were found to have a unique specific expression pattern that was coincident with the DOX-induced cardiomyopathy in diabetic hearts. Correspondingly, NF-κB expression in diabetic hearts was increased together with the elevation of S100A8/9 and activation of p38 MAPK signaling after DOX administration, which induced cardiac inflammation as demonstrated by the elevation of cardiac IL-6 level. These findings provide novel pre-clinical information for revealing the S100A8/A9-associated molecular signaling pathways that mediate the doxorubicin-induced cardiotoxicity in diabetic hearts.

Abstract 256: Ablation of 14-3-3 Protein Exacerbates Doxorubicin Induced Cardiomyopathy: Role of Apoptosis Signal Regulating Kinase-1

Background: 14-3-3η family members are dimeric phosphoserine-binding proteins that participate in signal transduction and checkpoint control pathways. Anthracycline anticancer drug doxorubicin (Dox) can induce cardiotoxicity, which is believed to be based on inflammatory or oxidative injury. However, the role of 14-3-3η is not clear in Dox induced cardiac injury. We examined the role of 14-3-3η protein and apoptosis signal-regulating kinase-1 (Ask1) and inflammatory signaling by using transgenic mice with cardiac-specific expression of a dominant-negative 14-3-3η protein mutant (DN 14-3-3) in Dox induced cardiac injury. Methods: Cardiac dysfunction was induced by a single injection of Dox into wild-type (WT) and DN 14-3-3η mice. By the end of the study, echocardiography was performed to assess the cardiac function. The heart tissues were used for histopathology and western blotting. Results: Left ventricular (LV) fractional shortening and ejection fraction were dramatically decreased in DN 14-3-3η mice, when compared to WT mice after Dox injection. Inactivation of 14-3-3η protein significantly increased Dox induced mortality. Significant Ask1 activation in DN 14-3-3η after Dox injection was evidenced by pronounced de-phosphorylation at Ser-967 and intense immunofluorescence observed LV sections. Marked increase in myocardial apoptosis, cardiac hypertrophy, and fibrosis were observed with a corresponding up-regulation of proinflammatory factors and cytokine expression in DN 14-3-3η mice after Dox injection. Furthermore cardiac expression of high mobility group box (HMGB)1 and its cascade protein expressions were significantly up-regulated in DN 14-3-3η mice compared to WT mice after Dox injection. Conclusion: Taken together, these findings suggest that depletion of 14-3-3η protein causes reduce survival rate in mice with cardiac dysfunction, presumably via activation of downstream Ask1 signaling pathways. This may provide a novel therapeutic strategy against Dox-induced cardiac injury by regulating Ask1 signaling.

The Relationship Between Left Ventricular Wall Thickness, Myocardial Shortening, and Ejection Fraction in Hypertensive Heart Disease: Insights From Cardiac Magnetic Resonance Imaging.

Hypertensive heart disease is often associated with a preserved left ventricular ejection fraction despite impaired myocardial shortening. The authors investigated this paradox in 55 hypertensive patients (52±13 years, 58% male) and 32 age- and sex-matched normotensive control patients (49±11 years, 56% male) who underwent cardiac magnetic resonance imaging at 1.5T. Long-axis shortening (R=0.62), midwall fractional shortening (R=0.68), and radial strain (R=0.48) all decreased (P<.001) as end-diastolic wall thickness increased. However, absolute wall thickening (defined as end-systolic minus end-diastolic wall thickness) was maintained, despite the reduced myocardial shortening. Absolute wall thickening correlated with ejection fraction (R=0.70, P<.0001). In multiple linear regression analysis, increasing wall thickness by 1 mm independently increased ejection fraction by 3.43 percentage points (adjusted β-coefficient: 3.43 [2.60-4.26], P<.0001). Increasing end-diastolic wall thickness augments ejection fraction through preservation of absolute wall thickening. Left ventricular ejection fraction should not be used in patients with hypertensive heart disease without correction for degree of hypertrophy.

67. Do prenatal intracardiac echogenic foci affect postnatal cardiac function?

Echogenic foci in the prenatal hear is not an uncommon finding. To determine whether prenatally diagnosed intracardiac echogenic foci are associated with neonatal cardiac dysfunction and persistence. Fetuses in which intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center from (September 2009 to December 2013) underwent postnatal echocardiography at ages 1 month to1 year. A single pediatric cardiologist assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid valve regurgitation was also sought. Prenatally 60 fetuses had intracardiac echogenic foci mean age ± SD at diagnosis (23 ± 3.1). 53 (88.3%) had left ventricular intracardiac echogenic foci, and 7 (11.6%) had right ventricular intracardiac echogenic foci. 12 preganant ladies were lost for follow up (2 fetuses of 7 (28.5%) with right ventricular intracardiac echogenic foci., and 10 fetuses of 53 (18.8%) with LV intracardiac echogenic foci %). Post natally, those infants, 32 (66.6%) males and 16 (33.3%) females were examined. At a mean age ± SD of 7.4 ± 3.1 months. Prenatally, all infants had a normal left ventricular shortening fraction. The overall mean left ventricular myocardial performance index (reference value, 0.36 ± 0.06), was normal for both infants with left ventricular intracardiac echogenic foci (0.32 ± 0.01) and those with right ventricular intracardiac echogenic foci (0.33 ± 0.05). Trace tricuspid valve regurgitation were noted in 15 (31%) of the infants. Left ventricular intracardiac echogenic foci persisted in 15 infants (34.8%), whereas right ventricular intracardiac echogenic foci persisted in 1 infant (20%). Prenatally diagnosed intracardiac echogenic foci can be persistent but is not associated with myocardial dysfunction in the first year of life.