Improvement In Cardiac Function Research Articles

Play Badminton Forever: A Systematic Review of Health Benefits.

Regular physical activity (PA) engagement has multiple benefits for individual general health at all ages and life stages. The present work focuses on badminton, which is one of the most popular sports worldwide. The aim was to conduct a systematic review focused on examining and analysing this sport and the benefits it brings to the health of those who engage in it. Examination was conducted from the viewpoint of overall health and provides an overview of the current state-of-the-art as presented in published scientific literature. PRISMA 2020 guidelines were adhered to. An exhaustive search was conducted of four electronic databases or search engines: Web of Science, Scopus, MEDLINE and Google Scholar. The search terms used were “badminton AND health” and “badminton AND benefits”. In total, 27 studies were eligible for inclusion in the systematic review. After analysing the results, it was concluded that badminton engagement may lead to an improvement in all areas, the most studied being those related to physical health, in particular the improvement of cardiac and pulmonary functions and the development of basic physical capacities.

Immunosuppressive therapy in virus-negative inflammatory cardiomyopathy: 20-year follow-up of the TIMIC trial.

AimsLong-term results of the Tailored IMmunosuppression in virus-negative Inflammatory Cardiomyopathy (TIMIC) trial protocol have been evaluated.Methods and resultsEighty-five patients with endomyocardial biopsy-proven virus-negative chronic inflammatory cardiomyopathy were enrolled in the randomized, double-blind, placebo-controlled TIMIC trial and received prednisone and azathioprine (n = 43) vs. placebo (n = 42) for 6 months. Immunosuppressive treatment promoted an improvement in cardiac function in 88% of the cases compared with none of the patients in the placebo group, which were switched to a 6-month immunosuppressive therapy at the end of the 6-month study period. Long-term (up to 20 years) clinical outcomes of the whole cohort of 85 patients originally enrolled in the TIMIC trial (Group A) were compared with those of a 1:2 propensity score-matched control cohort of patients untreated with the TIMIC protocol (Group B) and followed for a comparable period of time. The primary outcome was a composite of cardiovascular death and heart transplantation. At long-term follow-up, the risk of cardiovascular death [hazard ratio (HR) 6.77; 95% confidence interval (CI) 2.36–19.45] and heart transplantation (HR 7.92; 95% CI 1.80–34.88) was significantly higher in Group B patients. Group A showed a persistent improvement in the left ventricular ejection fraction compared with Group B (HR 7.24; 95% CI 3.05–17.18). A higher number of Group B patients underwent implantable cardioverter defibrillator implantation. The incidence of recurrent myocarditis was similar between groups, and patients with evidence of a recurrent cardiac inflammatory process promptly responded to a TIMIC protocol application.ConclusionVirus-negative inflammatory cardiomyopathy benefits from immunosuppressive therapy even after long-term follow-up. Recurrence appears to respond to a new TIMIC protocol application.

Benefits of esmolol in adults with sepsis and septic shock: An updated meta-analysis of randomized controlled trials.

Background:Sepsis affects millions of patients annually, resulting in substantial health and economic burdens globally. The role of esmolol potentially plays in the treatment of sepsis and septic shock in adult patients remains controversial.Methods:We undertook a systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases from their inception to May 12, 2022, for randomized controlled trials that evaluated the efficacy of esmolol for sepsis and septic shock. A random-effects meta-analysis was performed. Two investigators independently screened articles, extracted data, and assessed the quality of included studies.Results:Eight studies from 7 randomized controlled trials were included in our meta-analysis of 503 patients with sepsis and/or septic shock. Compared with standard treatment, esmolol significantly decreased 28-day mortality (risk ratio 0.68, 95% confidence interval [CI] 0.52–0.88; P = .004), heart rate (standardized mean difference [SMD] −1.83, 95% CI −2.95 to −0.70, P = .001), tumor necrosis factor-a (SMD −0.48, 95% CI −0.94 to −0.02, P = .04), and the troponin I level (SMD −0.59, 95% CI −1.02 to −0.16, P = .008) 24 hours after treatment. No significant effect was found in terms of length of intensive care unit stay; mean arterial pressure, lactic acid, central venous pressure, or central venous oxygen saturation, interleukin 6, or white blood cell levels; stroke volume index; or the PaO2/FiO2 ratio.Conclusions:Esmolol treatment may be safe and effective in decreasing 28-day mortality, controlling heart rate, and providing cardioprotective function, but has no effect on lung injury in patients with sepsis or septic shock after early fluid resuscitation. Improvement in cardiac function may be related to changes in serum inflammatory mediators. No significant adverse effects on tissue perfusion and oxygen utilization were observed.

Proteomics Revealed That Mitochondrial Function Contributed to the Protective Effect of Herba Siegesbeckiae Against Cardiac Ischemia/Reperfusion Injury.

BackgroundMyocardial ischemia/reperfusion (I/R) injury is the main obstacle to percutaneous coronary intervention, lacking effective therapeutic measures in a clinical setting. Herba Siegesbeckiae (HS) is a traditional herb with multiple pharmacological activities and evidence of cardiovascular protection. However, few data are available regarding the role of HS in cardiac I/R. This study aimed to explore the effect and underlying mechanism of HS aqueous extract on cardiac I/R injury.Materials and MethodsHerba Siegesbeckiae aqueous extract was prepared and analyzed by UHPLC-MS/MS. After intragastric administration of HS once daily for 7 days, male Sprague-Dawley rats were subjected to 30 min occlusion of the left anterior descending coronary artery followed by 120 min reperfusion to elicit I/R. Various parameters like myocardial infarction and apoptosis, 12-lead ECG and hemodynamics, cardiac morphology and myocardial enzymes, quantitative proteomics, mitochondrial ultrastructure and electron transport chain (ETC) function, oxidative stress and antioxidation, and NLRP3 inflammasome and inflammation were evaluated.ResultsThe chemical constituents of HS aqueous extract were mainly divided into flavonoids, diterpenoids, and organic acids. In vivo, HS aqueous extract notably alleviated myocardial I/R injury, as evidenced by a reduction in infarct size, apoptotic cells, and cardiac lesion enzymes; decline of ST-segment elevation; improvement of cardiac function; and preservation of morphology. Quantitative proteomics demonstrated that HS reversed the alteration in the expression of Adgb, Cbr1, Decr1, Eif5, Uchl5, Lmo7, Bdh1, Ckmt2, COX7A, and RT1-CE1 after I/R. In addition, HS preserved myocardial ultrastructure and restored the function of mitochondrial ETC complexes following exposure to I/R; HS significantly suppressed I/R-elicited increase of ROS, RNS, MDA, and 8-OHdG, restrained the acetylation of MnSOD, and recovered the activity of MnSOD; and HS reversed I/R-induced elevation of NLRP3 inflammasome and inhibited the release of inflammatory factors and pyroptosis.ConclusionHerba Siegesbeckiae aqueous extract ameliorated cardiac I/R injury, which is associated with mitigating oxidative stress, suppressing NLRP3 inflammasome, and restoring mitochondrial function by regulating the expression of Adgb, Cbr1, Decr1, Eif5, Uchl5, Lmo7, Bdh1, Ckmt2, COX7A, and RT1-CE1.

Marked improvements in cardiac function in postmenopausal women exposed to blood withdrawal plus endurance training

ABSTRACT The cardiac phenotype of a substantial fraction of the population, i.e., mature women, is mainly unresponsive to endurance training (ET), the most effective intervention to improve cardiorespiratory fitness. This study assessed whether a novel intervention comprising additional haemodynamic stimuli may overcome the generalized limitations to modify the cardiac phenotype of middle-aged and older women. Fifteen healthy postmenopausal women (52–75 yr) were recruited. Transthoracic echocardiography and central haemodynamics were assessed during incremental cycle ergometry (i) in baseline conditions, (ii) after standard (10%) blood withdrawal and (iii) subsequent 8-week ET. Main outcomes such as left ventricular (LV) function and structure and blood volume (BV) were determined. Phlebotomy induced a 0.5 ± 0.1 l reduction of BV, which was re-established after ET. Decrements in LV end-systolic volume (−27%) and increments in LV ejection fraction (+8%) during exercise as well as improved E/A ratio were detected after ET compared with baseline. In parallel, ET induced a 10% increment in LV mass without a concomitant increase in LV size. In conclusion, postmenopausal women exhibit large improvements in cardiac systolic and diastolic functions along with LV concentric remodelling in response to the sequenced combination of blood withdrawal and ET.

Cell-Free Treatments: A New Generation of Targeted Therapies for Treatment of Ischemic Heart Disease.

Although recent progress in medicine has substantially reduced cardiovascular diseases (CVDs)-related mortalities, current therapeutics have failed miserably to be beneficial for all patients with CVDs. A wide array of evidence suggests that newly-introduced cell-free treatments (CFTs) have more reliable results in the improvement of cardiac function. The main regeneration activity of CFTs protocols is based on bypassing cells and using paracrine factors. In this article, we aim to compare various stem cell secretomes, a part of a CFTs strategy, to generalize their effective clinical outcomes for patients with CVDs. Data for this review article were collected from 70 published articles (original, review, randomized clinical trials (RCTs), and case reports/series studies done on human and animals) obtained from Cochrane, Science Direct, PubMed, Scopus, Elsevier, and Google Scholar) from 2015 to April 2020 using six keywords. Full-text/full-length articles, abstract, section of book, chapter, and conference papers in English language were included. Studies with irrelevant/insufficient/data, or undefined practical methods were excluded. CFTs approaches involved in growth factors (GFs); gene-based therapies; microRNAs (miRNAs); extracellular vesicles (EVs) [exosomes (EXs) and microvesicles (MVs)]; and conditioned media (CM). EXs and CM have shown more remarkable results than stem cell therapy (SCT). GF-based therapies have useful results as well as side effects like pathologic angiogenesis. Cell source, cell′s aging and CM affect secretomes. Genetic manipulation of stem cells can change the secretome’s components. Growing progression to end stage heart failure (HF), propounds CFTs as an advantageous method with practical and clinical values for replacement of injured myocardium, and induction of neovascularization. To elucidate the secrets behind amplifying the expansion rate of cells, increasing life-expectancy, and improving quality of life (QOL) for patients with ischemic heart diseases (IHDs), collaboration among cell biologist, basic medical scientists, and cardiologists is highly recommended.

Beneficial properties of the biosynthesized silver/chitosan nanoparticles mediated by Mentha piperita in rats with heart failure following myocardial infarction

• The recent bio-nanocomposite has antioxidant activities against DPPH. • The recent bio-nanocomposite has therapeutic activities. • The recent bio-composite has been synthesized as the best. In this study, we report the green synthesis of nontoxic, stable, and small size silver nanoparticle by using chitosan/ Mentha piperita extract with reducing/capping ability without any toxic reducing agents. Mentha piperita was used as a reducing agent for the synthesis of Ag NPs that next stabilized by chitosan polymers. The in situ prepared Ag NPs/CS- Mentha piperita bio-composite were characterized by advanced physicochemical techniques like FE- SEM, TEM, EDX and XRD study. It has been established that Ag NPs/CS- Mentha piperita bio-composite have a spherical shape with a mean diameter from 5 to 15 nm. In heart failure model, the rats were subjected to coronary artery ligation, and orally administered with Ag NPs/CS- Mentha piperita 12.5, 25 and 50 µg kg(-1) daily, from the 7th day after surgery. Administration with Ag NPs/CS- Mentha piperita led to a significant reduction in infarct size and improvement in cardiac function as demonstrated by lower left ventricular end diastolic pressure (LVEDP) and elevated +/-dp/dt(max). We found that Ag NPs/CS- Mentha piperita significantly reduced left ventricular (LV)/body weight ratio, lung/body weight ratio and significantly inhibited neurohormonal activation. The antioxidant activity of Ag NPs/CS- Mentha piperita bio-composite was determined by DPPH method. The Ag NPs/CS- Mentha piperita bio-composite showed the high antioxidant activity according to the IC 50 value.

Naltrexone-Induced Cardiac Function Improvement is Associated With an Attenuated Inflammatory Response and Lipid Perioxidation in Volume Overloaded Rats.

In previous studies, upregulation of myocardial opioid receptors as well as the precursors of their endogenous ligands were detected in the failing heart due to chronic volume overload. Moreover, opioid receptor blockade by naltrexone improved left ventricular function. In parallel, inflammatory processes through cytokines have been confirmed to play an important role in the pathogenesis of different forms of heart failure. Thus, the present study examined the systemic and myocardial inflammatory response to chronic volume overload and its modulation by chronic naltrexone therapy. Chronic volume overload was induced in male Wistar rats by applying an infrarenal aortocaval fistula (ACF) for 28 days during which the selective opioid receptor antagonist naltrexone (n = 6) or vehicle (n = 6) were administered via a subcutaneously implanted Alzet minipump. The ultrastructural, morphometric and hemodynamic characterization of ACF animals were performed using an intraventricular conductance catheter in vivo and electron microscopy in vitro. Co-localization of mu-, delta- and kappa-opioid receptor subtypes (MOR, DOR, and KOR respectively) with the voltage gated L-type Ca2+ channel (Cav1.2), the ryanodine receptor (RyR), and mitochondria in cardiomyocytes as well as IL-6, IL-12, TNF-alpha, and Malondialdehyde (MDA) were determined using double immunofluorescence confocal microscopy, RT-PCR and ELISA, respectively. In rat left ventricular myocardium, three opioid receptor subtypes MOR, DOR, and KOR colocalized with Cav1.2, RyR and mitochondria suggesting a modulatory role of the excitation-contraction coupling. In rats with ACF-induced volume overload, signs of heart failure and myocardial ultrastructural damage, chronic naltrexone therapy improved cardiac function and reversed the systemic and myocardial inflammatory cytokine expression as well as lipid peroxidation. In conclusion, antagonism of the cardiodepressive effects of the myocardial opioid system does not only improve left ventricular function but also blunts the inflammatory response and lipid peroxidation.

Homoarginine treatment of rats improves cardiac function and remodeling in response to pressure overload

Low serum concentrations of the amino acid homoarginine (HA) are associated with increased cardiovascular mortality by incompletely understood mechanisms. This study sought to assess the influence of HA on cardiac remodeling in rats undergoing either transaortic banding or inhibition of nitric oxide synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Male Wistar rats (n= 136) underwent sham operation (SH) or aortic banding (AB). Both groups were equally divided into 14 subgroups, receiving different doses of HA alone or in combination with lisinopril, spironolactone, or L-NAME for 4weeks. HA treatment in AB animals resulted in a dose-dependent improvement of cardiac function up to a concentration of 800 mg·kg-1 ·day-1 . Combining 800 mg·kg-1 ·day-1 HA with spironolactone or lisinopril yielded additional effects, showing a positive correlation with LV ejection fraction (+33%, p= 0.0002) and fractional shortening (+41%, p= 0.0014). An inverse association was observed with collagen area fraction (-41%, p< 0.0001), myocyte cross-sectional area (-22%, p< 0.0001) and the molecular markers atrial natriuretic factor (-74%, p= 0.0091), brain natriuretic peptide (-42%, p =0.0298), beta-myosin heavy chain (-46%, p =0.0411), and collagen type V alpha 1 chain (-73%, p =0.0257) compared to placebo-treated AB animals. Co-administration of HA and L-NAME was found to attenuate cardiac remodeling and prevent NO-deficient hypertension following AB. HA treatment has led to a dose-dependent improvement of myocardial function and marked histological and molecular changes in cardiac remodeling following AB. Combining HA with standard heart failure medication resulted in additional beneficial effects boosting its direct impact on heart failure pathophysiology.

Role of Echocardiography in the Management of Patients with Advanced (Stage D) Heart Failure Related to Nonischemic Cardiomyopathy.

Echocardiography (ECHO) is indispensable for evaluation of patients with terminal chronic heart failure (HF) who require transplantation or mechanical circulatory support by a left- or biventricular assist device (LVAD or BiVAD, respectively). In LVAD candidates, ECHO represents the first-line investigation necessary for a timely discovery of heart-related risk factors for potentially life-threatening post-operative adverse events, including identification of patients who necessitate a biventricular support. ECHO is also required for intra-operative guiding of VAD implantation and finding of the most appropriate setting of the device for an optimal ventricular unloading, postoperative surveillance of the VAD support, and monitoring of the RV changes in LVAD recipients. Thanks to the ECHO, which has decisively contributed to the proof that prolonged VAD support can facilitate cardiac reverse remodeling and functional improvement to levels which allow successful weaning of carefully selected patients from LVAD or BiVAD, the previous opinion that chronic non-ischemic cardiomyopathy (NICMP) is irreversible could be refuted. In patients with normalized and stable right heart catheter-derived hemodynamic parameters obtained at short-term interruptions of VAD support, ECHO has proved able to predict post-weaning long-term freedom from HF recurrence in patients with pre-implant terminal chronic NICMP. The purpose of this article is to offer an actualized theoretical and practical support for clinicians engaged in this particularly challenging and topical issue especially due to the new practical aspects which have emerged in conjunction with the growing use of long-term ventricular assist devices as bridge-to-transplantation or as destination therapy, as well as the increasing evidence that, in some patients, such VAD can become a bridge-to-recovery, allowing the removal of the device after a longer support time.

Sacubitril/valsartan in an experimental model of heart failure with preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Ministry for Education, University and Research Introduction The majority of elderly patients with heart failure has a preserved ejection fraction (HFpEF) that constitutes a syndrome characterized by frequent hospitalizations and high mortality. Despite the growing social burden of HFpEF, the comprehension of its pathophysiology is incomplete, and treatment remains largely undefined. Aging itself may contribute independently to deterioration of diastolic function. Methods 18-month old female Fischer 344 rats were treated with oral administration of either sacubitril/valsartan (60 mg/kg/die, 1:1 ratio) or valsartan alone (30 mg/kg/die) for 12 weeks. Tail-cuff method was used to monitor blood pressure weekly. Echocardiography and left ventricle catheterization were employed to assess systolic and diastolic function, at baseline, and before sacrifice. Cardiac tissue was used for molecular biology and histochemistry assays. Results Tail-cuff analysis indicated a comparable decrease in blood pressure between treatments. Hypertrophy also showed a significant reduction with both treatments. On the contrary, myocardial function analysis demonstrated that no treatment was efficacy on diastolic dysfunction. The lack of improvement of cardiac function could be attributed to the inability of the treatments to counteract the accumulation of fibrotic tissue in the left ventricle, which, in turn, is attributable to the failure to reduce the inflammatory process and oxidative stress, and to the inability to modulate angiotensin II pathway. Conclusion Our results evidenced that both sacubitril/valsartan or valsartan treatment was able to improve diastolic function and pro-fibrotic remodeling, partly due to a lack of effect on classical and non-classical pathways of angiotensin II.

Adrenomedullin Improves Cardiac Remodeling and Function in Obese Rats with Hypertension.

This study aimed to determine whether adrenomedullin (ADM, 7.2 μg/kg/day, ip), an important endogenous active peptide, has a protective role in cardiac remodeling and function in obesity-related hypertension (OH) rats. A high-fat diet (HFD) was used to induce OH for 20 weeks. H9c2 cells incubated with palmitate (PA, 200 μM) to mimic high free fatty acid in obesity were used as an in vitro model. In OH rats, ADM not only decreased body weight (BW) and blood pressure (BP) but also improved systemic inflammation and oxidative stress. Moreover, ADM still had a greater inhibitory effect on local inflammation and oxidative stress in the hearts of OH rats, and the same anti-inflammatory and antioxidant effects were also confirmed in PA-treated H9c2 cells. The ADM receptor antagonist or Akt inhibitor effectively attenuated the inhibitory effects of ADM on inflammation and oxidative stress in PA-stimulated H9c2 cells. Furthermore, ADM application effectively normalized heart function, and hematoxylin-eosin and Masson staining and collagen volume fraction results showed that ADM improved cardiac remodeling in hearts of OH rats. ADM attenuated cardiac inflammation and oxidative stress via the receptor-Akt pathway, which involves the improvement of cardiac remodeling and function in OH rats.

Response to triheptanoin therapy in critically ill patients with LC-FAOD: Report of patients treated through an expanded access program.

Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of inborn errors of metabolism wherein patients are unable to process long-chain fatty acids into useable energy in the mitochondria. LC-FAOD commonly affects organ systems with high energy demand, manifesting as hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy, rhabdomyolysis, and skeletal myopathy, as well as peripheral neuropathy and retinopathy in some subtypes. Collectively, LC-FAOD have a high mortality rate, especially in cases of early onset disease, and in the presence of cardiomyopathy. Triheptanoin is a synthetic medium-odd chain triglyceride, produced using a GMP-compliant process, which was designed to replenish mitochondrial metabolic deficits and restore energy homeostasis. Prior to its approval, triheptanoin was only available through clinical trials or to seriously ill patients as part of an expanded access program (EAP) following physician request. This retrospective study examined the impact of triheptanoin on cardiovascular parameters, in critically ill patients who participated in the EAP from February 2013 to January 2018. These patients persisted in critical condition despite receiving standard treatment in highly qualified centers by expert metabolic physicians and dietitians. Physician-completed questionnaires and narrative summaries were used to evaluate the disease presentation and management prior to the trigger event leading to triheptanoin request and use, and the response to triheptanoin treatment. Following triheptanoin initiation, most patients survived the initial trigger event (e.g., severe urinary tract infection, pneumonia) and demonstrated improvements in both short-term and long-term LC-FAOD manifestations. In patients with cardiomyopathy, stabilization or improvement from pretreatment levels was reported in left ventricular ejection fraction and left ventricular mass, in particular, all infants with cardiomyopathy showed improvement in cardiac function during triheptanoin therapy. Triheptanoin therapy was generally well tolerated. The study results are consistent with the existing positive benefit/risk profile of triheptanoin and reflect the effect of triheptanoin improving cardiac function in patients experiencing severe episodes of metabolic decompensation despite standard therapy.

Complete Revascularization Showed A Better Cardiac Function Improvement In Patients With Low Ejection Fraction.

This study aimed to compare postoperative ejection fraction (EF) in response to coronary artery bypass grafting (CABG) among patients with preoperative EF <35% and >35%. A retrospective study was conducted in a single institution using clinical data of 660 patients undergoing elective on-pump CABG in 2018-2019. Patients were classified into two groups based on preoperative left ventricle ejection fraction (<35% and >35%). The primary endpoint was the change of postoperative ejection fraction. In this study, 72 patients had preoperative left ventricle ejection fraction <35% (group A) while the other 588 patients had ejection fraction >35% (group B). Among both groups, the duration of cardiopulmonary bypass (CPB) and aortic clamp (AxC) were not significantly different (P > 0.05). The transformation of pre- and postoperative EF in groups A and B was significantly different (2.91+10.31 vs. -0.14+4.57, P < 0.001). There was a significant difference in the duration of ICU stay (73.42+112.55 vs. 34.43+64.99, P < 0.001) and postoperative ventilatory support (25.54+43.92 vs. 16.42+45.87, P < 0.008) between group A and B. Low preoperative EF showed better improvement in cardiac function after surgery. We concluded that the result could be affected by revascularization of hibernating myocardium.

Responders to Sodium-Glucose Cotransporter 2 Inhibitors in Improving Left Ventricular Function

Sodium-glucose cotransporter 2 inhibitor (SGLT2i)-incorporated medical therapy is associated with cardiac function improvement in patients with heart failure. However, the factors associated with such an improvement remain unknown.This study included patients with heart failure and type 2 diabetes mellitus who received SGLT2i-incorporated medical therapy in our institute. Transthoracic echocardiography was performed at baseline and 3-18 months later. The factors associated with cardiac function improvement were investigated.A total of 47 patients (median age, 69 years old; 35 men) were included in this study. SGLT2i was administered for median 284 days (range: 86-730 days). The left ventricular ejection fraction increased from 39.0% to 54.0% (P < 0.001), and the E/e' ratio decreased from 14.0 to 10.4 (P = 0.002). Younger age, higher serum albumin level, and lower serum sodium level were independently associated with an improvement in systolic function, defined as an increase in the ejection fraction of ≥ 35% among patients with systolic heart failure (P = 0.018). Male sex and impaired renal function tended to be associated with an improvement in diastolic function, defined as a decrease in the E/e' ratio of ≥ 20% among the overall cohort.Several factors were associated with improvements in systolic and diastolic functions during the SGLT2i-incorporated medical therapy.

L-Carnitine Alleviates the Myocardial Infarction and Left Ventricular Remodeling through Bax/Bcl-2 Signal Pathway

Purpose L-carnitine (LC) is considered to have good therapeutic potential for myocardial infarction (MI), but its mechanism has not been clarified. The aim of the study is to elucidate the cardioprotective effects of LC in mice following MI and related mechanisms. Methods ICR mice were treated with LC for 2 weeks after induction of MI with ligation of left anterior descending artery. Electrocardiographic (ECG) recording and echocardiography were used to evaluate cardiac function. H&E staining, TTC staining, and Masson staining were performed for morphological analysis and cardiac fibrosis. ELISA and immunofluorescence were utilized to detect biomarkers and inflammatory mediators. The key proteins in the Bax/Bcl-2 signaling pathway were also examined by Western blot. Results Both echocardiography and histological measurement showed an improvement in cardiac function and morphology. Biomarkers such as LDH, NT-proBNP, cTnT, and AST, as well as the inflammatory cytokines IL-1β, IL-6, and TNF-α, were decreased in plasma of mice receiving LC treatment after myocardial injury. In addition, the expression of α-SMA as well as the key proteins in the Bax/Bcl-2 signaling pathway in cardiac myocardium were much lower in mice with LC treatment compared to those without after MI. Conclusions Our data suggest that LC can effectively ameliorate left ventricular (LV) remodeling after MI, and its beneficial effects on myocardial function and remodeling may be attributable at least in part to anti-inflammatory and inhibition of the Bax/Bcl-2 apoptotic signaling pathway.

The effects of chronic, dose-dependent administration of dronedarone and amiodarone on cardiodynamics and oxidative stress parameters of isolated rat heart with hypertension

Abstract Funding Acknowledgements Type of funding sources: None. Background Amiodarone represents the most widely used antiarrhythmic drug with an indication for administration in heart failure (HF) with many of its side effects. Dronedarone reduces the risk of recurrent atrial fibrillation, with increased mortality due to worsening HF, but necessary experimental data is missing. Purpose Investigate chronic, dose-dependent effects of Dronedarone and Amiodarone on cardiodynamic and oxidative stress of spontaneusly hypertensive rat (SHR) heart. Methods The present study was carried out on 42 SHR Wistar Kyoto male rats: Control (n=6), and 6 experimental groups treated by oral lavage for 4 weeks: rats treated with 100 mg/kg of Amiodarone (n=6), rats treated with 50 mg/kg of Amiodarone (n=6), rats treated with 10 mg/kg of Amiodarone (n=6), rats treated with 50 mg/kg of Dronedarone (n=6), rats treated with 10 mg/kg of Dronedarone (n=6) and rats treated with 5 mg/kg of Dronedarone (n=6). Isolated rat hearts were perfused by Langendorff perfusion apparatus and following cardiodynamic parameters were continuously registered: dp/dt max, dp/dt min, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate and coronary flow on each of predetermined values of coronary perfused pressure. Parameters of oxidative stress were determined spectrophotometrically. Results Amiodarone in the low dose significantly improved dp/dt max and dt/dt min, this effect was less pronounced in the middle dose of Amiodarone, while Amiodarone in the high dose significantly decreased all parameters of cardiac function. Amiodarone in low dose significantly increased levels of parameters of oxidative stress including levels of O2- and nitrites, when compared to other doses of Amiodarone. Significant changes in cardiac function were also observed in Dronedarone treated rats, however function was significantly decreased in all Dronedarone groups. Dronedarone severely depressed cardiac function with dose-dependent effect. Comparison between Amiodarone and Dronedarone groups revealed that Amiodarone was better in improvement of cardiac function in all dose-regimes (Figure 1). Dronedarone significantly lowered levels of H2O2 and TBARS without dose-dependent effect, concentrations of O2-, NO2- remained unchanged. Amiodarone increased O2-, NO2- and TBARS with a dose-dependent effect. When compared to Amiodarone, Dronedarone lowered all oxidative stress parameters in high, middle and low-dose (Figure 2.) Conclusion Dose-dependent, chronic administration of Dronedarone severely depressed SHR cardiac function. Amiodarone shows less pronaunced effects in high and middle dose, while low dose increased cardiac function. By comparing the effects of Amiodarone and Dronedarone, Amiodarone showed better effects on SHR cardiac function in all doses, while Dronedarone significantly reduced parameters of oxidative stress in all doses, when compared to their parallel doses of Amiodarone.

Efficacy and Dosage Pattern of Sacubitril/Valsartan in Chinese Heart Failure with Reduced Ejection Fraction Patients

This study aims to investigate the dosage pattern, efficacy, and safety of sacubitril/valsartan (Sac/Val) in Chinese heart failure with reduced ejection fraction (HFrEF) patients regarding real-world settings. Patients from 27 centers with a confirmed diagnosis of HFrEF and initiated Sac/Val treatment were enrolled. The primary objective was to evaluate the dosage pattern and change of heart failure status. In a final cohort of 983 patients, outpatient Sac/Val treatment demonstrated a similar beneficial effect in NT-proBNP and cardiac function. After initiating the treatment, overall and sub-population showed similar safety and efficacy. Patients who received a higher dose of Sac/Val (> 200 mg/d) demonstrated better improvement in LV function and reduction of NT-proBNP regardless of adjustment. Among Chinese HFrEF patients, Sac/Val showed a comparable reduction in NT-proBNP and improvement in cardiac function. Data further support guideline recommendations of Sac/Val in Chinese population. Optimal up-titration might provide further benefits. Further long-term and prognostic studies are needed.Graphical abstract

Anti‐depressant lithium compounds reliefs cardiorespiratory disturbances and improves cardiac function in experimental non‐ischemic heart failure

Non‐ischemic heart failure (HF) is a complex medical problem with a high incidence among the older population. While several efforts have been made to improve HF outcomes there is an urgent need for new strategies to reduce mortality rates. Sympathoexcitation and disordered breathing are both considered hallmarks of HF and are closely related to disease progression. Lithium salts has been largely used as anti‐depressants; however, lithium compounds also showed several pleiotropic effects some of them linked to the origin of cardiorespiratory disorders in HF (i.e. oxidative stress). Accordingly, using drug repurposing strategy we aimed to define whether lithium treatment improve cardiorespiratory function in experimental HF. Male Sprague‐Dawley rats underwent volume overload to induce non‐ischemic HF. Four weeks after HF induction, an osmotic minipump containing lithium chloride (Li+, 2 meq/Kg/day) was subcutaneously implanted for drug delivery. Cardiac autonomic and baroreflex function, ventilatory chemoreflex drive and disordered breathing were evaluated after 4 weeks of Li+ treatment in freely moving rats. In addition, cardiac function was determine using PV‐loops. Compared to Sham rats, HF animals displayed autonomic imbalance, reduced baroreflex sensitivity, higher incidence of cardiac arrhythmias, enhanced central chemoreflex and breathing disorders. Cardiac diastolic dysfunction was evident in HF animals compared to Sham animals. HF rats that underwent Li+ treatment showed significant (p&lt;0.05) improvements in cardiac autonomic function as evidenced by reduced low‐to‐high frequency ratio of heart rate variability (LF/HF: 2.8 ± 0.3 vs. 0.9 ± 0.4; HF+Veh vs. HF+Li+), baroreflex sensitivity (BRS: 2.0 ± 0.5 vs. 5.8 ± 1.0 ms/mmHg; HF+Veh vs. HF+Li+) and reduced cardiac arrhythmogenesis (PVC: 220 ± 50 vs. 30 ± 10 events/h; HF+Veh vs. HF+Li+). Furthermore, Li+ treatment in HF completely normalized central chemoreflex drive. Indeed, hypercapnic ventilatory responses obtained in HF+Li+ rats were undistinguishable from the ones obtained in Sham rats (HCVR: 1.7 ± 0.4 vs. 2.0 ± 0.4 DVe/FiCO2; HF+Veh vs. HF+Li+). Also, breathing disorders (i.e. apneas/hypopneas) were markedly reduced by Li+ treatment in HF (AHI: 8.5 ± 1.0 vs. 3.7 ± 0.8; HF+Veh vs. HF+Li+). Lastly, HF+Li+ treated rats displayed marked improvements in cardiac diastolic function (~2.5‐fold reduction in EDPVR) compared to HF+Veh treated rats. We found that the beneficial effects of Li+were partially associated with upregulation of the Nrf2 pathway and related antioxidant genes (i.e. SOD2), reductions in tissue oxidative stress and decreases in the expression of pro‐inflammatory cytokines (i.e. TNF‐a) in HF rats. Our results support the notion that lithium compounds may offer new avenues for the treatment of cardiorespiratory disorders and cardiac diastolic dysfunction in non‐ischemic HF.

Abstract 330: Kinin B1r Inhibitor Prevents Sepsis-induced Cardiac Dysfunction And Promotes Survival In Mice

Introduction: Hyperpermeability of the microvascular barrier and the resulting capillary leakage are hallmarks of sepsis. B1R has been proposed to be a therapeutic target for sepsis-induced microvascular hyperpermeability and multiorgan failure. However, its direct role in regulating of cardiac function during severe sepsis remains poorly characterized. Hypothesis: We hypothesized that B1R inhibition can protect against sepsis-induced cardiac dysfunction and improve survival. Methods and Results: To address the hypothesis, we pre-treated mice with either vehicle (control) or a specific B1R antagonist B6929via subcutaneous injection then subjected them to 40% cecal ligation and puncture (CLP) to induce polymicrobial sepsis. Serum levels of IL-6 and TNFα increased significantly within 4 hours post-CLP in the controls. However, B1R antagonist treatment abolished CLP-induced expressions of IL-6 and TNFα by 70% and 30%, respectively. B1R antagonist also protected mice from sepsis-induced organ failure—as highlighted by the lowered increase in MSS score over the 24-h post-CLP—resulting in significant improvement in survival rate (P&lt;0.05). In-vivo cardiac vascular permeability assessed using the Miles assay further demonstrated that B1R inhibition prevented sepsis-induced cardiac microvascular leakage and edema. Similar improvements were also observed in the liver and kidney. Further study revealed an early cardioprotective effect of B1R inhibitor, as evidenced by the improvement of EF%, FS%, and cardiac output in mice treated with B1R antagonist + CLP vs. CLP alone (p&lt;0.01) from the echocardiogram analyses at 4-6 hours following CLP. Furthermore, mitochondrial H 2 O 2 measurement of the freshly isolated cardiac mitochondria from septic mice also showed that B1R inhibition partially abolished the production of H 2 O 2 . The opening of mPTP was also reduced with B1Ri treatment. Taken together, these findings indicated improvement in cardiac mitochondrial function following B1R inhibitor treatment. Conclusions: Our findings provide novel insights into the pathogenesis of sepsis-induced cardiac mitochondrial dysfunction and heart failure. Inhibition of B1R may be a novel therapeutic strategy for sepsis-associated cardiovascular disease.