Left Ventricular Internal Dimension In Systole Research Articles

Artificial intelligence technology applied to an unoccluded catheter for recognition of hemodynamic changes

This study seeks to provide a reliable means for physicians to diagnose hemorrhagic complications associated with patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. We employ the YOLOv4 algorithm to analyze cardiac parameters from the echocardiography device's ultrasonic wave, such as left ventricular ejection time (LVET), left ventricular internal dimension-diastole (LVIDd), left ventricular internal dimension-systole (LVIDs), posterior wall thickness at end-systole (HES), and RR interval. The proposed model has achieved an impressive average detection accuracy of 89.4% for these five parameters. Additionally, the further evaluation of cardiac function can be done by deriving the end-systolic wall stress (ESWS) and left ventricle rate-corrected mean velocity of circumferential fiber shortening (mVcFc) values from these parameters. As a result, it indicates that the accuracy of ESWS and mVcFc values is 88.7% and 90.3%, respectively. With this deep learning-based approach, physicians can confidently evaluate the cardiac function of ELBW infants and diagnose PDA-related hemorrhagic complications.

Overexpression of NR4A2 alleviates renal and myocardial injury in diabetes nephropathy rats through the HDAC11/SPRY1 pathway.

Diabetic nephropathy (DN) remains the most prevalent cause of end-stage renal disease. Nuclear receptor subfamily 4 group A member 2 (NR4A2) is a nuclear receptor with unique physiological characteristics. This study explored the molecular mechanism of NR4A2 in renal and cardiac functions of DN rats. A rat model of DN was established by intraperitoneal injection of streptozocin. NR4A2, histone deacetylase 11 (HDAC11), and sprouty 1 (SPRY1) expressions were detected. The fasting blood glucose (FBG), urinary albumin (UAlb), serum creatinine (Cr), and blood urea nitrogen (BUN) were determined. The pathological injury of renal and myocardial tissues was evaluated. The mitral early to late diastolic flow velocity ratio (E/A ratio), left ventricular ejection fraction (LVEF), left ventricular systolic function (LVSF), left ventricular internal dimension systole (LVIDs), and left ventricular internal diameter diastole (LVIDd) were tested, and the levels of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were examined. The enrichment of NR4A2 in HDAC11 promoter and enrichment of H3K27 acetylation in SPRY1 promoter were measured. NR4A2 and SPRY1 were downregulated while HDAC11 was upregulated in renal and myocardial tissues of DN rats. NR4A2 overexpression reduced FBG, UAlb, Cr, and BUN, alleviated pathological injury of renal and myocardial tissues, elevated the E/A ratio, LVEF, and LVFS, but reduced LVIDs, and decreased serum cTnI and CK-MB. NR4A2 depressed HDAC11 expression by binding to the HDAC11 promoter. HDAC11 repressed SPRY1 transcription by suppressing the H3K27ac level. HDAC11 overexpression or SPRY1 inhibition reversed the alleviating effect of NR4A2 overexpression on DN rats. NR4A2 was poorly expressed in DN rats. NR4A2 overexpression suppressed HDAC11 expression by binding to the HDAC11 promoter and enhanced SPRY1 transcription by enhancing H3K27 acetylation, thereby alleviating the renal and myocardial injury of DN rats.

Effect of Yanshiqiangxin Decoction on Cardiomyocyte Apoptosis in Heart Failure Rats Based on PI3K/Akt/Caspase-9 Signaling Pathway

<bold>Objective</bold> To detect the effect of Yanshiqiangxin decoction on apoptosis of cardiomyocytes in rats with heart failure based on PI3K/Akt/Caspase-9 signalling pathway and to explore the possible mechanism of Yanshiqiangxin decoction in the treatment of heart failure. <bold>Methods</bold> A total of 60 Wistar male rats were randomly divided into the normal group, the model group, the low dose Yanshiqiangxin decoction group, the medium dose Yanshiqiangxin decoction group,the high dose Yanshiqiangxin decoction group and the Perindopril group according to the random number table method, with 10 cases in each group. Except for the normal group, the remaining five groups were modelled by injecting adriamycin solution to induce myocardial injury and to establish the rat model of heart failure. In the low, medium and high dose Yanshiqiangxin decoction groups, 4.325, 8.65 and 17.3 g/(kg·d) of raw drug were administered by gavage respectively; the Perindopril group was given perindopril solution by gavage at the dose of 4 mg/(kg·d). The gavage dose was calculated as 10 mL/(kg·d) ,the normal group and the model group were given the same volume of distilled water. One day after the last gavage, M-mode echocardiography [left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular internal dimension diastole (LVIDd) and left ventricular internal dimension systole (LVIDs)] was performed through an ultra-high resolution small animal ultrasound imaging system; B-type natriuretic peptide (BNP) was measured by ELISA method; the apoptosis of cardiomyocytes was observed through laser confocal microscopy and the apoptosis index was calculated; the expression of apoptosis-related proteins Bax, Bcl-2 and PI3K/Akt/Caspase-9 signalling pathway proteins were detected by Western blot method. <bold>Results</bold> ① Cardiac ultrasound test results: compared with the normal group, the left ventricular anterior wall motion waveform of the model group was not obvious, close to linear motion, and LVEF and LVFS decreased significantly (<italic>P</italic>&lt;0.05), LVIDd and LVIDs increased significantly (<italic>P</italic>&lt;0.05), the left ventricle was significantly enlarged and the contractility was reduced. Compared with the model group, the amplitude of left ventricular anterior wall motion waveform increased at different degrees in the low, medium and high dose Yanshiqiangxin decoction group, LVEF and LVFS gradually increased with the increase of administration concentration (<italic>P</italic>&lt;0.05), while LVIDd decreased only in the medium dose Yanshiqiangxin decoction group (<italic>P</italic>&lt;0.05), LVIDs of the medium dose Yanshiqiangxin decoction group and the high dose Yanshiqiangxin decoction group were significantly reduced, the medium dose Yanshiqiangxin decoction group decreased the most significantly (<italic>P</italic>&lt;0.05). ② Serum BNP results: compared with the normal group, BNP of the model group was significantly increased (<italic>P</italic>&lt;0.05). Compared with the model group, BNP of the low, medium and high dose Yanshiqiangxin decoction group was significantly decreased, BNP gradually decreased with the increase of administration concentration (<italic>P</italic>&lt;0.05). ③ Myocardial histopathology results: Cardiomyocytes had no apoptosis and almost no positive signal was detected in the normal group; compared with the model group,the number of cardiomyocyte apoptosis of the low, medium, high dose Yanshiqiangxin decoction group and the perindopril group was significantly decreased, the number of cardiomyocyte apoptosis gradually decreased with the increase of administration concentration (<italic>P</italic>&lt;0.05). ④ PI3K/Akt/Caspase-9 signaling pathway protein expression levels and apoptotic factors: compared with the model group, PI3K and Akt protein expression, Bcl-2 content and Bcl-2/Bax ratio of the low, medium and high dose Yanshiqiangxin decoction group were significantly increased, PI3K and Akt protein expression, Bcl-2 content and Bcl-2/Bax ratio gradually increased with the increase of administration concentration (<italic>P</italic>&lt;0.05); Caspase-9 and Caspase-3 protein expression of the low, medium and high dose Yanshiqiangxin decoction group were significantly decreased, Bax content of the medium and high dose Yanshiqiangxin decoction group were significantly decreased, and gradually increased with the increase of administration concentration (<italic>P</italic>&lt;0.05). <bold>Conclusions</bold> Yanshiqiangxin decoction can improve cardiac function, reduce the content of BNP in serum and cardiomyocyte apoptosis, the mechanism may be related to the regulation of the PI3K/Akt/Caspase-9 signalling pathway.

LuQi Formula Ameliorates Myocardial Fibrosis by Suppressing TLR4/MyD88/NF-κB Pathway and NLRP3 Inflammasome Activation in Mice with Myocardial Infarction.

Background Myocardial fibrosis caused by myocardial infarction (MI) is the key factor leading to cardiac remodeling; nod-like receptor family pyrin domain-containing 3 (NLRP3) plays an important role in regulation of myocardial injury; however, its relationship with TLR4/MyD88/NF-κB signaling pathway is largely unreported. In recent years, traditional Chinese medicine (TCM) prevention and treatment of cardiovascular diseases has shown its unique advantages and broad application prospects. LuQi Formula (LQF) has been used for more than 20 years in Shuguang Hospital (Shanghai, China), and it was confirmed that it can improve the clinical symptoms of patients after MI. Here, we investigated the mechanism of LQF by suppressing NLRP3 inflammasome activation and TLR4/MyD88/NF-κB pathway in mice with MI. Purpose The purpose of this study was to verify the positive effects of the LQF in ameliorating myocardial fibrosis and inflammasome infiltration in the MI mice in vivo. Methods Forty mice were randomized into four groups: the sham group, the MI group, the LQF group, and the perindopril group (n = 10 per group). Left anterior descending (LAD) coronary artery ligation was performed in all groups except the sham group. The mice were treated with LQF after MI. After 4 weeks, LDH, cTnI, IL-1β, and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) kit, and cardiac function was evaluated by echocardiography. Hematoxylin and eosin (H&E) and Masson staining were used to evaluate the myocardial injury and fibrosis. Western blot was used to evaluate the expression of collagen I, α-SMA, NLRP3 inflammasome, and TLR4/MyD88/NF-κB signaling pathway. Immunohistochemical analysis was used to further detect the expression of Fibronectin, α-SMA, collagen I, collagen III, NLRP3, and NF-κB in myocardial tissue. Results Compared with the MI group, the ejection fraction (EF) and fractional shortening (FS) in the LQF group were significantly improved, while the left ventricular end diastolic diameter (LVEDd) and left ventricular internal dimension systole (LVIDs) were significantly decreased. The representative staining of H&E and Masson showed that treatment with LQF could effectively reduce myocardial injury and fibrosis. ELISA results showed that serum LDH, cTnI, TNF-α, IL-18, and IL-1β in LQF group were significantly lower than those in MI group. The western blot results showed that the expressions of collagen I and α-SMA were decreased significantly in the LQF group. Moreover, the expressions of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathway were downregulated in the LQF treatment group. Conclusion Our results suggested that LQF could significantly improve cardiac function and ameliorate myocardial fibrosis. In addition, we found that LQF could downregulate the TLR4/MyD88/NF-κB signaling pathway and then inhibit the activation of NLRP3 inflammasome, suggesting that LQF alleviated cardiac fibrosis by decreasing the TLR4/MyD88/NF-κB signaling pathway and then inhibited NLRP3 inflammasome activation in MI mice, which indicates potential therapeutic effect of LQF on patients with MI.

Retrospective study of dilated cardiomyopathy in dogs.

BackgroundThe United States Food and Drug Administration is investigating possible diet‐associated dilated cardiomyopathy (DCM) in dogs and cats.ObjectivesTo retrospectively review DCM cases for signalment, diet information, echocardiographic changes, and survival.AnimalsClient‐owned dogs (n = 71).MethodsMedical records of dogs diagnosed with DCM between January 1, 2014 and September 30, 2018 were reviewed. Dogs were grouped into “traditional” or “nontraditional” diet categories and whether or not diet was changed after diagnosis.ResultsFor dogs eating nontraditional diets, those that had their diets changed had a larger percentage decrease in normalized systolic left ventricular internal dimension (P = .03) and left atrial:aorta ratio (P < .001) compared to those that did not have their diets changed. Survival time was significantly longer for dogs with DCM eating nontraditional diets that had their diets changed (median survival, 337 days; range, 9‐1307 days) compared to dogs eating nontraditional diets that did not have their diets changed (median survival, 215 days; range, 1‐852 days; P = .002).Conclusions and Clinical ImportanceDogs with DCM eating nontraditional diets can experience improvement in cardiac function after diet change but additional research is needed to examine possible associations between diet and DCM.

Shenmai Injection Improves Energy Metabolism in Patients With Heart Failure: A Randomized Controlled Trial.

BackgroundIn recent years, the application of Shenmai (SM) injection, a traditional Chinese medicine (TCM), to treat heart failure (HF) has been gradually accepted in China. However, whether SM improves energy metabolism in patients with HF has not been determined due to the lack of high-quality studies. We aimed to investigate the influence of SM on energy metabolism in patients with HF.MethodsThis single-blind, controlled study randomly assigned 120 eligible patients equally into three groups receiving SM, trimetazidine (TMZ), or control in addition to standard medical treatment for HF for 7 days. The primary endpoints were changes in free fatty acids (FFAs), glucose, lactic acid (LA), pyroracemic acid (pyruvate, PA) and branched chain amino acids (BCAAs) in serum. The secondary outcomes included the New York Heart Association (NYHA) functional classification, TCM syndrome score (TCM-s), left ventricular injection fraction (LVEF), left ventricular internal diastolic diameter (LVIDd), left ventricular internal dimension systole (LVIDs), and B-type natriuretic peptide (BNP).ResultsAfter treatment for 1 week, the NYHA functional classification, TCM-s, and BNP level gradually decreased in the patients in all three groups, but these metrics were significantly increased in the patients in the SM group compared with those in the patients in the TMZ and control groups (P < 0.05). Moreover, energy metabolism was improved in the NYHA III–IV patients in the SM group compared with those in the patients in the TMZ and control groups as evidenced by changes in the serum levels of FFA, LA, PA, and BCAA.ConclusionsIntegrative treatment with SM in addition to standard medical treatment for HF was associated with improved cardiac function compared to standard medical treatment alone. The benefit of SM in HF may be related to an improvement in energy metabolism, which seems to be more remarkable than that following treatment with TMZ.

Effects of simulated high-altitude hypobaric hypoxia on cardiac structure and function in rats

To investigate the effects of simulated hypobaric hypoxia environment at 7 000 m above sea level on cardiac structure and function in rats. A total of 96 male SD rats were randomly divided into high-altitude hypobaric hypoxia group (hypoxia group) and normobaric normoxia group (control group). Rats of hypoxia group were placed in a large cabin simulated 7 000 m high-altitude hypobaric hypoxia environment. Operating time 23 h / d, the control circadian ratio of approximately 12 h:12 h. The rats in control group were bred under normobaric normoxia. The hypoxic group was divided into 3 d, 7 d, 14 d, 28 d groups according to hypoxic time, 12 rats in each group. Changes of structure and function of heart due to hypoxia were evaluated by echocardiography and electrocardiogram. Myocardial pathological changes were analyzed by hematoxylin-eosin staining(HE). Compared with the control group at the same time point ①With prolonged exposure to hypobaric hypoxia, the growth ratio of body mass in rats is slower. Arterial oxygen saturation was significantly lower in both 14 d and 28 d (P＜0.05). ② Left ventricular end-diastolic anterior wall thickness (LVAWD) and left ventricular end-diastolic posterior wall thickness (LVPWD) of rats in 28 d were increased significantly (P＜0.05). Left ventricular end-diastolic diameter (LVIDD) and left ventricular internal dimension systole (LVIDS) of rats in 28 d were decreased significantly (P＜0.05, P＜0.01). Left ventricular ejection fraction (EF), fractional shortening of left ventricle (FS), pulmonary vein (PV) peak velocity and PV peak gradient of rats in 7 d were decreased significantly (P＜0.05, P＜0.01). ③The QRS and QT interval period were significantly prolonged in 14 d and 28 d (P＜0.05, P＜0.01). The ST was significantly lower in 3 d and 7 d (P＜0.05, P＜0.01). The amplitude of R wave gradually shifted downward in 7 d, 14 d, 28 d (P＜0.05, P＜0.01). ④The red blood cell (RBC), hemoglobin (HGB), red blood cell distribution width (RDW) in hypoxic group were increased significantly (P＜0.01). The platelet count (PLT) count was decreased significantly in 14 d and 28 d (P＜0.01). The serum creatinine (CR) was increased significantly in 14 d and 28 d (P＜0.05). ⑤Pathological changes such as myocardial edema, sarcolemma condensate, focal degeneration and necrosis with inflammatory cell infiltration could be found at early stage of hypoxia. Myocardial compensatory repair such as myocardial fibroblasts proliferation was significant at end stage of hypoxia. Left ventricular systolic functions of rats were decreased significantly after exposure to high altitude hypoxia hypobaric. The left ventricular systolic functions would recovery compensatory after one week exposed to high altitude hypoxia hypobaric.

Rosuvastatin reduces the pro-inflammatory effects of adriamycin on the expression of HMGB1 and RAGE in rats.

Rosuvastatin has cardiac protective effects through its anti-inflammatory effects. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from dying cells. The present study aimed to investigate the effects of rosuvastatin in adriamycin (ADR)-treated rats. Adult male rats were randomized to three groups: i) Control group, ii) ADR group, and iii) ADR+rosuvastatin group. Serum biochemical indices were measured using an enzyme-linked immunosorbent assay. Cardiac function was assessed by echocardiography. The expression of HMGB1 and receptors for advanced glycation end products (RAGE) were assessed by reverse transcription-quantitative polymerase chain reaction analysis, western blot analysis, and immunohistochemistry. Cytokines were measured using flow cytometry. Rosuvastatin improved the biochemical indices and cardiac morphology and alleviated the pathological lesions. In the ADR+rosuvastatin group, the mRNA and protein levels of HMGB1 and RAGE in the myocardium were significantly lower compared with those in the ADR group (both P<0.05). The results showed that rosuvastatin significantly reduced the levels of HMGB1 and RAGE in the myocardium of the ADR-treated rats. These results suggest that the protective effects of rosuvastatin may be associated with attenuation of the HMGB1/RAGE-mediated inflammatory response in ADR-treated rats. Despite this protective effect of rosuvastatin in the present study, it did not improve cardiac function in terms of the diastolic left ventricular internal dimension, systolic left ventricular internal dimension, left ventricular ejection fraction and left ventricular fractional shortening; this may be due the observation duration being insufficient.

The effects of hyperoxia liquid regulate cardiopulmonary bypass‑induced myocardial damage through the Nrf2‑ARE signaling pathway

The aim of the present study was to investigate the protective role of hyperoxia liquid in regulating cardiopulmonary bypass (CPB)‑induced myocardial damage and its possible underlying mechanism. In the CPB‑induced rat model, hyperoxia liquid enhanced left ventricular ejection fraction (LVEF), reduced the left ventricular internal dimension systole (LVIDs) level, inhibited malondialdehyde levels, increased superoxide dismutase, glutathione (GSH) and GSH peroxidase levels, suppressed heart cell apoptosis, and induced the nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) signaling pathway. Then, ML385, a Nrf2 inhibitor, was used to attenuate the effect of hyperoxia liquid on LVEF and LVIDs levels, oxidative stress and heart cell apoptosis in the CPB‑induced rat model. Collectively, the results of the present study demonstrated that the protective role of hyperoxia liquid may regulate oxidative stress in a CPB‑induced rat model through the Nrf2‑antioxidant response element signaling pathway.

Effects of Lower Limb Cycle Training on Echocardiographic Parameters of Left Ventricle in Dilated Cardiomyopathy Patients.

To determine the effect of lower limb ergometric training on echocardiographic parameters of left ventricle in dilated cardiomyopathy (DMC) patients. Randomized control trial. Rawalpindi Institute of Cardiology, Rawalpindi, Pakistan, from September 2016 to February 2017. Clinically stable patients with DCM (n=60), were randomly allocated into an interventional group with two-month interventional program and a non-trained control group (n=30 each). Treatment protocol for interventional group was lower limb ergometer exercise for 8 weeks, 4 days/week. Pre and post-treatment echocardiography was done in both groups at baseline and after 8 weeks. SPSS 21 was used for data analysis. The median (IQR) age of the patients was 51 (18) years in interventional group and 62 (11) years in control group. Male to female ratio was 18:9 in control group and 17:12 in Interventional group. Statistically significant results were detected within the groups regarding ejection fraction (EF), left ventricular internal dimension systole (LVIDS) and left ventricular internal diastolic dimension (LVIDD) (p <0.001). Exercise training with lower limb ergometer was effective in improving the ejection fraction and left ventricular dimensions in patients with dilated cardiomyopathies.

Novel Roles for Obscurin Proteins in Cardiac Muscle

Obscurin is a giant myofibrillar protein important for sarcomere structure, signaling, and maintenance of sarcoplasmic reticulum (SR) organization. Surprisingly, obscurin knockout mice develop normally and only show signs of a mild skeletal muscle myopathy. However, little is known about cardiac functions of obscurin. We characterized cardiac roles of obscurin and found no changes to cardiac physiology. One explanation for the lack of a cardiac phenotype in obscurin knockout mice is that other obscurin protein family members possess a functionally redundant role. We hypothesized that obscurin-like 1 (Obsl-1) is responsible for this redundancy, in part due to its shared ability to bind the sarcomeric proteins titin and myomesin. We generated double knockout (dKO) mice by crossing the obscurin-KO mice with a cardiac specific Obsl1-KO line to investigate the roles for these proteins in cardiac development and function. Although a majority of the dKO-mice died after 12 months of age, microscopic and ultrastructural analysis failed to reveal overt changes to sarcomere organization. Dramatic changes were observed, however, in SR structure and function. Specifically we observed: 1.) loss of SR structural integrity and apparent loss of SR content, and 2.) alterations to Ca2+ transients and in the levels of Ca2+ handling proteins in KO animals. The majority of these changes were more severe in dKO-mice. Furthermore, we employed serial blockface TEM technology to precisely measure the volume of the SR and mitochondria and noticed significant differences between KO and control animals. Physiologically, these mice develop a late onset cardiomyopathy characterized by increased systolic left ventricular internal dimension and alterations in hemodynamic properties at ∼12 mo. of age. Our data suggests that obscurin and Obsl1 are not critical for sarcomerogenisis, however are important for jointly organizing SR organization, cellular Ca2+ handling, and long-term survival in mice.

Prevention of doxorubicin induced cardiomyopathy after delivery of modified acidic fibroblast growth factor by using ultrasound-targeted microbubble destruction: a preliminary experimental study

Objective To observe the preventive effects of doxorubicin-induced cardiomyopathy (DOX-CM) rats after delivery of modified acidic fibroblast growth factor (MaFGF) by using ultrasound-targeted microbubble destruction (UTMD). Methods Fifty male SD rats were randomly divided into five groups: ①Control group; ②DOX-CM group; ③MaFGF group; ④UTMD group; ⑤MaFGF+ UTMD group. ②~⑤groups were intraperitoneally injected with doxorubicin to induce DOX-CM and given the corresponding interventions. Six weeks after intervention, all rats were underwent conventional echocardiography and velocity vector imaging (VVI) exams. Left ventricular internal dimension-diastole (LVIDd), left ventricular internal dimension-systole (LVIDs), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured using conventional echocardiography. The segmental mean peak systolic radial velocity (Vs), systolic radial strain (Sr), and systolic radial strain rate (SRr) of six walls at the papillary muscle level were measured in left ventricular short-axis view by VVI. At last, myocardial tissues of all rats were stained with HE to observe the myocardial tissue morphology and with Van Gieson (VG) to calculate the collagen volume fractions (CVF). Results Six weeks after intervention, heart weight/body weight (HW/BW), LVIDs and LVIDd of MaFGF+ UTMD group were significantly decreased compared with those of DOX-CM group(P<0.05), while the LVEF, LVFS, Vs, Sc and Sr were significantly increased (P<0.05). Van Gieson stains showed that the collagen volume fractions (CVF) of DOX-CM groups significantly increased compared with that of the control group (P<0.01), while the CVF of MaFGF+ UTMD groups significantly decreased (P<0.01). Conclusions Delivery of MaFGF to myocardium in DOX-CM rats by UTMD could retard the formation of myocardial fibrosis and effectively protect the left ventricular function of DOX-CM rats. Key words: Echocardiography; Microbubbles; Acidic fibroblast growth factor; Cardiomyopathy; Doxorubicin

Quality of Life Score as a Predictor of Death in Dogs with Degenerative Mitral Valve Disease.

BackgroundThe knowledge of the variables predicting mortality is important in clinical practice and for therapeutic monitoring in mitral valve disease.ObjectivesTo determine whether a quality of life score evaluated with the Functional Evaluation of Cardiac Health questionnaire would predict mortality in dogs with degenerative mitral valve disease (DMVD).MethodsThirty-six client-owned dogs with mitral valve disease underwent clinical, laboratory, and echocardiographic evaluations at baseline and were monitored for 6 months. Cardiovascular death was the primary outcome.ResultsThe 36 dogs were classified as survivors or nonsurvivors. Higher values of the following variables were obtained at baseline in the nonsurviving group (12 dogs): amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, plasma norepinephrine, heart rate, quality of life score, diastolic left ventricular internal dimension to aortic root ratio, systolic left ventricular internal dimension to aortic root ratio, and left atrium to aortic root ratio. NT-proBNP levels and quality life score were independently associated with death in the multivariable analysis.ConclusionThe quality life score was an independent variable for cardiac death in dogs with DMVD. This result is encouraging, as this score is easy to apply and does not require any technology, only a veterinarian and an observant owner.

Alterations in echocardiographic left ventricular function after percutaneous coronary stenting in diabetic patients with isolated severe proximal left anterior descending artery stenosis

BackgroundThere are conflicting theories regarding the use of percutaneous coronary intervention (PCI) of isolated severe proximal left anterior descending (LAD) artery stenosis in place of left internal mammary artery grafting in diabetic patients. The aim of this study was to investigate the effect of PCI on left ventricular function and determine difference between diabetics and non-diabetics. MethodsA prospective study was conducted on 50 patients with isolated severe proximal LAD stenosis: 23 diabetic and 27 non-diabetic patients. Successful PCI with everolimus-eluting stents was performed for all of the patients. These patients underwent transthoracic echocardiography within 24h before and 1 month after PCI, and alterations in the left ventricular parameters were compared between the two groups. ResultsThere was a significant 12% increment in the mitral annular peak systolic velocity (s′) (p=0.02), 21% decrement in the trans mitral early filling deceleration time (DT) (p<0.001), 10% decrement in the systolic left ventricular internal dimension (LVIDs) (p=0.002), significant increment in the left ventricular ejection fraction (LVEF) (p=0.004), and significant decrement in the left atrial diameter (p=0.006) in the diabetic patients after performing PCI. Conversely, the non-diabetic patients showed a statistically significant 14% increase in the DT, 6.3% decrease in the s′ velocity, 8% increase in the LVIDs, significant increment in the left atrial diameter and no change in LVEF after PCI. ConclusionOur study demonstrated that everolimus-eluting stents favorably improved the markers of left ventricular systolic and diastolic function in diabetic patients with isolated severe proximal LAD stenosis compared with those of non-diabetic patients with the same condition.

Abnormal left ventricular relaxation and symptoms of heart failure

The purpose of our study was to assess the echocardiographic and angiographic parameters in patients with symptomatic heart failure (HF) and mild diastolic dysfunction (grade I). It remains uncertain why some patients with mild diastolic dysfunction exhibit HF symptoms and others are asymptomatic. The study enrolled 80 hospitalized patients with impaired left ventricular (LV) relaxation. Patients were divided into two groups; one group had chronic functional class II to III dyspnea and the other group had no symptoms of HF. After admission, echocardiography and coronary angiography were performed for all patients and LV systolic and diastolic parameters were compared between the two groups. More patients in the asymptomatic group were hypertensive (p-value: 0.012). However, coronary artery disease was more prevalent in symptomatic patients (p-value: 0.022). The LV ejection fraction (EF) was significantly lower in symptomatic patients [median 54.33%, 95% confidence interval (53.76-54.87%) in asymptomatic patients and median 49.43, 95% confidence interval (47.23-50.91%) in symptomatic patients, p-value<0.001]. Furthermore, the systolic LV internal dimension was significantly larger in this group (p-value: 0.037). The results of logistic regression identified that only the absolute level of the LVEF was the negative determinant of the occurrence of HF in patients with impaired LV relaxation. Our study showed that LV systolic performance has an important role in occurrence of HF symptoms in patients with grade I diastolic dysfunction.

Possible mechanism by which renal sympathetic denervation improves left ventricular remodelling after myocardial infarction.

What is the central question of this study? The enzyme system that is responsible for extracellular matrix (ECM) turnover is the matrix metalloproteinases (MMPs), which can be blocked by the tissue inhibitors of MMPs (TIMPs). Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction left ventricular remodelling through attenuation of ECM via regulation of MMP activity and/or the MMP-TIMP complex remains unknown. What is the main finding and its importance? Renal sympathetic denervation has therapeutic effects on post-myocardial infarction left ventricular remodelling, probably by attenuating the ECM through regulation of the MMP9-TIMP1 complex in the transforming growth factor-β1 (a profibrotic cytokine that accelerates ECM remodelling after ischaemia) signalling pathway. Whether renal sympathetic denervation (RSD) is able to ameliorate post-myocardial infarction (post-MI) left ventricular (LV) remodelling by attenuation of the extracellular matrix via regulation of matrix metalloproteinase (MMP) activity and/or the MMP-tissue inhibitor of matrix metalloproteinase (TIMP) complex remains unknown. Sixty-five Sprague-Dawley rats were randomly divided into the following four groups: normal (N, n = 15), RSD (RSD, n = 15), myocardial infarction (MI, n = 15) and RSD 3 days after MI (MI3d+RSD, n = 20). The bilateral renal nerves were surgically denervated 3 days after MI had been induced by coronary artery ligation. Left ventricular function was assessed using echocardiography and a Millar catheter at 6 weeks post-MI. Plasma noradrenaline, angiotensin II and aldosterone, collagen volume fraction, transforming growth factor-β1 (TGF-β1), MMP2, MMP9 and TIMP1 in heart tissue were measured 6 weeks after MI. In rats with MI3d+RSD compared with MI rats, RSD improved systolic and diastolic function, resulting in an improvement in ejection fraction (P < 0.05), fractional shortening (P < 0.05) and LV internal dimension in systole (P < 0.05) and diastole (P < 0.05). Additionally, RSD treatment decreased left ventricular end-diastolic pressure (P < 0.05) and increased LV systolic pressure (P < 0.05) and maximal and minimal rate of LV pressure (both P < 0.05). Meanwhile, RSD reduced collagen content (P < 0.01). TIMP1 was upregulated (P < 0.05), whereas MMP2, MMP9 and TGF-β1 were downregulated in the LV of RSD-treated animals (P < 0.05). Renal sympathetic denervation has therapeutic effects on post-MI LV remodelling, probably owing to effects on the extracellular matrix by regulation of the MMP9-TIMP1 balance in the TGF-β1 signalling pathway. Renal sympathetic denervation may be considered as a non-pharmacological approach for the improvement of post-MI cardiac dysfunction.

Angiotensin Type 2 Receptor Stimulation Ameliorates Left Ventricular Fibrosis and Dysfunction via Regulation of Tissue Inhibitor of Matrix Metalloproteinase 1/Matrix Metalloproteinase 9 Axis and Transforming Growth Factor β1 in the Rat Heart

Left ventricular (LV) remodeling is the main reason for the development of progressive cardiac dysfunction after myocardial infarction (MI). This study investigated whether stimulation of the angiotensin type 2 receptor is able to ameliorate post-MI cardiac remodeling and what the underlying mechanisms may be. MI was induced in Wistar rats by permanent ligation of the left coronary artery. Treatment with the angiotensin type 2 receptor agonist compound 21 (0.03 mg/kg) was started 6 hours post-MI and continued for 6 weeks. Hemodynamic parameters were measured by echocardiography and intracardiac catheter. Effects on proteolysis were studied in heart tissue and primary cardiac fibroblasts. Compound 21 significantly improved systolic and diastolic functions, resulting in improved ejection fraction (71.2±4.7% versus 53.4±7.0%; P<0.001), fractional shortening (P<0.05), LV internal dimension in systole (P<0.05), LV end-diastolic pressure (16.9±1.2 versus 22.1±1.4 mm Hg; P<0.05), ratio of early (E) to late (A) ventricular filling velocities, and maximum and minimum rate of LV pressure rise (P<0.05). Compound 21 improved arterial stiffness parameters and reduced collagen content in peri-infarct myocardium. Tissue inhibitor of matrix metalloproteinase 1 was strongly upregulated, whereas matrix metalloproteinases 2 and 9 and transforming growth factor β1 were diminished in LV of treated animals. In cardiac fibroblasts, compound 21 initially induced tissue inhibitor of matrix metalloproteinase 1 expression followed by attenuated matrix metalloproteinase 9 and transforming growth factor β1 secretion. In conclusion, angiotensin type 2 receptor stimulation improves cardiac function and prevents cardiac remodeling in the late stage after MI, suggesting that angiotensin type 2 receptor agonists may be considered a future pharmacological approach for the improvement of post-MI cardiac dysfunction.

Abstract 259: The Role of Gender in Cardiac Resynchronization Therapy Response in Patients with Optimal Anatomical and Electrical Left Ventricular Lead Location.

Background: While optimal left ventricular (LV) lead location and the female sex are known to predict a favorable response to cardiac resynchronization therapy (CRT), the role of gender differences affecting CRT outcomes in patients with optimal LV lead location remains uncertain. Methods: We analyzed a prospective cohort of 180 CRT patients. Anatomical lead location was confirmed by coronary venograms and chest radiographs. LV lead electrical delay (LVLED) was measured from QRS onset on surface ECG to the first sensed signal of the LV lead, and standardized based on native QRS width. Echocardiographic response was evaluated at baseline and 6 months. Time to first heart failure hospitalization or death was assessed over 3 years. Results: 100 patients (Age 68.2 ± 12.3 years; Baseline LVEF 23.2 ± 6.8 %, NYHA 3.0 ± 0.3) with optimal LV lead location defined as ‘long’ LVLED (LVLED&gt;50%) with non-apical and anterolateral, lateral or posterolateral lead position were selected from the original cohort. They were further divided into the female (n=26) and male (n=74) groups. Baseline clinical characteristics were similar between groups except for a higher incidence of ischemic cardiomyopathy in males (72.4% vs. 47.1%, p=0.01) and longer QRS duration in females (171.3 ± 29.9 vs. 153.6 ± 26.9, p=0.008). Baseline echocardiographic characteristics revealed a smaller LV internal dimension in systole (LVIDs) and diastole (LVIDd) in females (51.7 ± 10.2 vs. 57.1 ± 8.9, p=0.02; 58.5% ± 10.1 vs. 64.5 ± 8.3, p=0.007 respectively). Survival with respect to first heart failure hospitalization (Figure 1A) and a composite of mortality and heart failure (Figure 1B) were comparable. Echocardiographic response, defined as an increase in mean LVEF by 10% was significant in females (+11.6 ± 11.0 % vs. +5.3 ± 9.0 %, p=0.01). Conclusion: In CRT patients with optimal lead location, females have superior outcomes with respect to reverse remodeling but gender differences donot appear to predict clinical outcomes.

β1 Integrin Gene Excision in the Adult Murine Cardiac Myocyte Causes Defective Mechanical and Signaling Responses

How mechanical signals are transmitted in the cardiac myocyte is poorly understood. In this study, we produced a tamoxifen-inducible mouse model in which β1 integrin could be reduced specifically in the adult cardiomyocyte, so that the function of this integrin could be assessed in the postnatal and mechanically stressed heart. The expression of β1 integrin was reduced to 35% of control levels, but function remained normal at baseline. With aortic constriction, the knockout mice survived but had a blunted hypertrophic response. Integrin knockout myocytes, in contrast to controls, showed reduced integrin-linked kinase expression both at baseline and after hemodynamic stress; focal adhesion kinase expression was reduced after stress. Alterations in multiple signaling pathways were detected in the integrin knockout group after acute and chronic hemodynamic stress. Most remarkably, when we challenged the knockout mice with short-term loading, the robust responses of several kinases (extracellular signal-regulated kinase 1/2, p38, and Akt) evident in control mice were essentially abolished in the knockout mice. We also found that reduction of myocyte β1 integrin expression modified adrenergic-mediated signaling through extracellular signal-regulated kinase, p38, and Akt. Reduction of β1 integrin expression in the mature cardiac myocyte leads to a varied response compared with when this protein is reduced during either the embryonic or perinatal period. These results show that β1 integrin expression is required for proper mechanotransductive and adrenergic responses of the adult heart.

English

To explore the effect of the angiotensin type 1 (AT-1) receptor antagonist, Irbesartan, on myocardial interstitial fibrosis in rats with diabetic cardiomyopathy (DCM). Thirty-nine male wistar rats were injected intraperitoneally with streptozotocin (STZ) (55 mg/kg, once) to establish a DCM animal model. After 12 weeks, the rats with blood glucose higher than 16.7 mmol/L, as well as polydipsiaa€hyperphagia and polyuria, were randomly divided into three groups: control, Irbesartan and A779+Irbesartan group. Rats in control were infused normal saline, in Irbesartan were infused Irbesartan (50 mg/kg) and in A779+Irbesartan were infused Irbesartan and were injected with A779 (100 ng/kg) once daily. At the end of the experiment, left ventricular internal dimension systole (LVIDs)a€left ventricular internal dimension diastole (LVIDd)a€E/Aa€left ventricular ejection fraction (LVEF)a€shortening fraction (FS) were measured. Then collagen content and the messenger ribonucleic acid (mRNA) expression of angiotensin-convertion enzyme 2 (ACE2) were detected. At the end of the experiment, the LVIDs, LVIDd and the collagen content of Irbesartan and A779+Irbesartan were significantly lower than control (P<0.01), E/A, FS, LVEF and the expression of ACE2 mRNA of Irbesartan and A779+Irbesartan were higher than control (P<0.01). The LVIDs, LVIDd and collagen content of A779+Irbesartan were higher than Irbesartan (P<0.05), E/A, FS, LVEF of A779+Irbesartan were lower than Irbesartan (P<0.05). However, there was no significant difference in the expression of ACE2 mRNA between Irbesartan and A779+Irbesartan. Irbesartan amelioorates myocardial interstitial fibrosis via angiotensin-(1-7) (Ang-(1-7)) Key words: Irbesartan, angiotensin-(1-7), angiotensin-convertion enzyme-2, A779, diabetes mellitus, cardiomyopathy.