Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process.METHODS A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay.RESULTS Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fcgroup.CONCLUSIONS In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.

Effects of Yerba Mate Consumption (Ilex paraguariensis) on Cardiac Remodeling in Rats

This study investigated the effects of yerba mate consumption, a South American beverage, on cardiac remodeling in rats. For this purpose, 24 male Wistar rats were divided into Control Group (CG) which received filtered water and a standard diet, and Yerba Mate Group (YM), 6 g of Ilex paraguariensis in 100 ml water and the same diet, for 30 days. The YM group showed a reduction in final body weight and food consumption without altering weight gain. Regarding cardiac remodeling, the YM group exhibited a decrease in the right ventricle weight/final body weight ratio, suggesting cardiac atrophy, without affecting the atria and left ventricle. There was no change in cardiomyocyte area or nuclear fractal dimension in both groups. However, animals that consumed yerba mate showed increased collagen deposition and a smaller fractal dimension in the left ventricle. The consumption of yerba mate at room temperature for 30 days induced changes in cardiac remodeling, as evidenced by increased collagen deposition and alterations in fractal dimension in the left ventricle.

Evidence-Based Complementary and Alternative Medicine Effects of Capybara Oil on Cardiac Remodeling of C57bl/6 Mice

Cardiovascular diseases are the main cause of morbidity and mortality in the world, and obesity and the metabolic syndrome are risk factors for its development. One of the therapies to reduce cardiovascular risk is the use of polyunsaturated fatty acids. In Brazil, a source of such acid is the oil extracted from the fat of the capybara. The objective of this work is to study the effects of the capybara oil on lipid and glucose metabolism, as well as its effects on the adipose tissue and cardiac remodeling. We assessed the effects of capybara oil treatment on body mass, lipid and carbohydrate metabolism, systolic blood pressure, adipose tissue and cardiac remodeling, and performed an ultrastructural evaluation of the myocardium in C57Bl/6 mice treated with high-fat diet. Treatment with capybara oil reduced total cholesterol and triglyceride levels, systolic blood pressure, visceral and subcutaneous adipose tissue, and adipocyte diameter. In addition, cardiac remodeling was attenuated, preserving cardiomyocytes, increasing vascularization, reducing cardiomyocyte hypertrophy and the extracellular matrix, and preserving the morphological integrity of mitochondria. Capybara oil has several beneficial effects on the cardiovascular and metabolic system, and further studies are needed to better understand its role in the prevention or treatment of cardiovascular diseases.

The impact of aging on cardiac remodeling in chronic mitral regurgitation

BACKGROUND Chronic mitral regurgitation(MR)is a volume overload state that causes dilatation of the left sided cardiac chambers.The presence of significant dilatation is considered an indication for mitral valve intervention,however,aging may affect left ventricular(LV)remodeling independently of valvular disease.The objective of this study was to examine age-related changes in cardiac remodeling in a broad population of patients with chronic MR.METHODS Consecutive subjects that underwent echocardiography examinations recorded in the echocardiography database of a university-affiliated laboratory were retrieved.Subjects were categorized into none/mild,moderate or severe MR.For purposes of analysis of differences with aging,the population was divided into groups above and below 70 years of age and standard echocardiographic measurements were compared between the groups.RESULTS A total of 3492 subjects with at least moderate MR(mean age:76 years,52%female)were included in the study and compared to 18,250 subjects with none or mild MR.Older patients had significantly smaller LV end-diastolic diameters and volumes and significantly larger left atrial(LA)volumes when compared to the younger group.LA volume index increased in both age groups as MR severity increased,while LV end-diastolic volume increased with increasing MR only in the younger population.CONCLUSIONS Cardiac remodeling in chronic MR is significantly influenced by age.Guideline based recommendations of timing of mitral valve interventions in asymptomatic MR patients,based on assessment of LA and LV remodeling,may need to take age into account.

Role of matricellular proteins in cardiac tissue remodeling after myocardial infarction

After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.

Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure

Objective We performed experiments using Neuregulin-1β （NRG-1β） treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions （GJs） during heart failure （HF）. Methods Rat models of I-IF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF （HF, n = 16）, NRG-1β trealanent （NRG, n = 16）, and sham operation （S, n = 16） group. The rats in the NRG group were administered NRG-1β （10 μg/kg per day） for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline, Twelve weeks after operation, Connexin 43 （Cx43） expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastmcture of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac fimction of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastmcture of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.

Effect of spironolactone on cardiac remodeling after acute myocardial infarction

BACKGROUND:Few studies have reported the effect of aldosterone receptor antagonist(ARA) on myocardial remodeling after acute myocardial infarction(AMI).This study was undertaken to investigate the preventive effect of ARA on myocardial remodeling after AMI.METHODS:A total of 616 patients who had been admitted into the CCU of the First Affiliated Hospital of Harbin Medical University from January 2008 to January 2010 were studied prospectively.Only 528 patients were observed completely,including 266 of the control group and 262 of the treatment group.There was no statistical difference in age,gender,medical history,admission situation,and treatment between the two groups(P>0.05).The preventive effects of spironolactone on cardiac remodeling,left ventricular function,renal function and blood levels of potassium were evaluated by echocardiography,serum potassium and serum creatinine at one-month and one-year follow-up.RESULTS:The echocardiography indicators such as LVESD,LVEDD,LVEF,LAD-ML and LADSI were significantly improved in the treatment group compared with the control group at one year(P<0.05).In the treatment group,LVESD,LVEDD,LVPWT,LVEF,LAD-ML and LAD-SI were more significantly improved at one year than one month(P<0.05,P=0.007 to LVEF),and in the control group LVEF was more significantly improved at one year than one month(P=0.0277).There were no significant differences in serum potassium and serum creatinine levels between the two groups.CONCLUSION:On the basis of conventional treatment,the early combination of low-dose spironolactone(20 mg/d) could inhibit cardiac remodeling at late stage and prevent heart fadure.

Pyroptosis is a drug target for prevention of adverse cardiac remodeling: The crosstalk between pyroptosis, apoptosis, and autophagy

Acute myocardial infarction(AMI)is one of the main reasons of cardiovascular disease-related death.The introduction of percutaneous coronary intervention to clinical practice dramatically decreased the mortality rate in AMI.Adverse cardiac remodeling is a serious problem in cardiology.An increase in the effectiveness of AMI treatment and prevention of adverse cardiac remodeling is difficult to achieve without understanding the mechanisms of reperfusion cardiac injury and cardiac remodeling.Inhibition of pyroptosis prevents the development of postinfarction and pressure overload-induced cardiac remodeling,and mitigates cardiomyopathy induced by diabetes and metabolic syndrome.Therefore,it is reasonable to hypothesize that the pyroptosis inhibitors may find a role in clinical practice for treatment of AMI and prevention of cardiac remodeling,diabetes and metabolic syndrome-triggered cardiomyopathy.It was demonstrated that pyroptosis interacts closely with apoptosis and autophagy.Pyroptosis could be inhibited by nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 inhibitors,caspase-1 inhibitors,microRNA,angiotensin-converting enzyme inhibitors,angiotensinⅡreceptor blockers,and traditional Chinese herbal medicines.

Increasing angiotensin-converting enzyme(ACE)2/ACE axes ratio alleviates early pulmonary vascular remodeling in a porcine model of acute pulmonary embolism with cardiac arrest

BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation.Pigs were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril.RESULTS:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells.Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control group.Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC.Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 expression.CONCLUSION:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.

Effect of trimetazidine combined with bisoprolol on the cardiac function, ventricular remodeling and neuroendocrine factors in patients with chronic heart failure

Objective:To study the effect of trimetazidine combined with bisoprolol on the cardiac function, ventricular remodeling and neuroendocrine factors in patients with chronic heart failure.Methods: A total of 52 patients with chronic heart failure who were treated in our hospital between January 2012 and November 2015 were collected and divided into the control group (n=26) who received bisoprolol therapy and the observation group (n=26) who received trimetazidine combined with bisoprolol therapy according to the double-blind randomized control method, and both groups were treated for 3 months. Before treatment and after 3 months of treatment, cardiac color Doppler diasonograph was used to determine the levels of cardiac function parameters and ventricular remodeling parameters, and RIA method was used to determine the levels if peripheral blood neuroendocrine factors.Results: Before treatment, the differences in cardiac function, ventricular remodeling and neuroendocrine factor levels were not statistically significant between two groups of patients. After 3 months of treatment, cardiac function parameters LVEDd and LVESD levels of observation group were lower than those of control group while LVEF level was higher than that of control group, and ventricular remodeling parameters LVPWT, IVSS, PWD, PWS and LVMI levels were lower than those of control group;peripheral blood neuroendocrine factors NE, ALD, AngⅡ, ANP and ET contents of observation group were lower than those of control group.Conclusion:Trimetazidine combined with bisoprolol can optimize the cardiac function, suppress the ventricular remodeling process and regulate the neuroendocrine factor secretion in patients with chronic heart failure, and it contributes to the patients' overall optimization.

Renal denervation for amelioration of cardiac remodeling in a swine model of chronic heart failure

Objective Overactivation of sympathetic nerve system is one of the main mechanism in post-MI myocardial remodeling even after early reperfusion, it eventually leads to heart failure. And renal denervation which targets at renal sympathetic nerves may have beneficial effects on cardiac remodeling. So we perform an experiment aiming to investigate the effect of RDN on cardiac remodeling and function.

Targeting PPARαin low ambient temperature exposure-induced cardiac dysfunction and remodeling

The present study demonstrates that the down-regulation of peroxisome proliferator-activated receptor-α(PPARα)results in chronic low ambient temperature(LT)exposure-induced cardiac dysfunction and remodeling,emphasizing the therapeutic potential of PPARαactivation strategies(e.g.,fenofibrate treatment)in LT-associated cardiac injury.

Protective effects of rice bran hydrolysates on heart rate variability,cardiac oxidative stress,and cardiac remodeling in high fat and high fructose diet-fed rats

Objective:To examine the ameliorative effect of rice bran hydrolysates(RBH)on metabolic disorders,cardiac oxidative stress,heart rate variability(HRV),and cardiac structural changes in high fat and high fructose(HFHF)-fed rats.Methods:Male Sprague-Dawley rats were daily fed either standard chow diet with tap water or an HFHF diet with 10%fructose in drinking water over 16 weeks.RBH(500 and 1000 mg/kg/day)was orally administered to the HFHF-diet-fed rats during the last 6 weeks of the study period.At the end of the treatment,metabolic parameters,oxidative stress,HRV,and cardiac structural changes were examined.Results:RBH administration significantly ameliorated metabolic disorders by improving lipid profiles,insulin sensitivity,and hemodynamic parameters.Moreover,RBH restored HRV,as evidenced by decreasing the ratio of low-frequency to highfrequency power of HRV,a marker of autonomic imbalance.Cardiac oxidative stress was also mitigated after RBH supplementation by decreasing cardiac malondialdehyde and protein carbonyl,upregulating eNOS expression,and increasing catalase activity in the heart.Furthermore,RBH mitigated cardiac structural changes by reducing cardiac hypertrophy and myocardial fibrosis in HFHFdiet-fed rats.Conclusions:The present findings suggest that consumption of RBH may exert cardioprotective effects against autonomic imbalances,cardiac oxidative stress,and structural changes in metabolic syndrome.

Modification of Serum Galectin-3 and Reversal of Cardiac Remodeling Following Pediatric Transcatheter Atrial Septal Defect Closure

Objectives:We aimed to evaluate the effect of percutaneous atrial septal defect(ASD)closure in children using right heart indices and serum galectin-3(Gal-3),as potential biomarkers of right heart remodeling.Methods:This case–control prospective study included 40 children with ASD and 25 control subjects.An echocardiographic evaluation was performed before the procedure,as well as 24 h,1 month,and 6 months after intervention.Serum Gal-3 was measured before,and 1 month after the procedure.Results:Serum Gal-3 concentration,right atrial(RA)dimensions,right ventricular(RV)dimensions,indexed RA area,and right index of myocardial performance(RIMP)were significantly increased in children with ASD compared with control subjects while tricuspid annular plane systolic excursion(TAPSE)was significantly decreased.Six months after closure,RA,and RV dimensions significantly decreased and RVfunction improved(RIMP decreased and TAPSE increased).Gal-3 oncentration significantly decreased 1 month after ASD closure,but it did not reach normal range compared with control subjects.A positive correlation between Gal-3 and age at closure,RA area,RV dimensions,and RIMP was observed.A positive correlation was observed between the decrease in Gal-3 concentration and the decrease in RA area and RV dimensions 1 month after ASD closure.A significant negative correlation was observed between TAPSE and Gal-3 concentration before and after intervention.Conclusions:Percutaneous ASD closure can improve right-sided indices and decrease serum Gal-3 concentration.Gal-3 can be used as a sensitive biomarker of right heart remodeling,with a decrease in Gal-3 concentration suggesting reversal of maladaptive remodeling.

Cardiac remodeling in postischemic end-stage human hearts: Involvement of extracellular matrix and angiogenesis-related molecules

Background: Extracellular matrix (ECM) participates in heart growth and influences cardiac stem-cell differentiation and migration. The modification of ECM associated with cardiomyopathies is a complex process involving a cohort of proteins. ECM proteins are involved in the regulation of neoangiogenesis in physiological and pathological conditions through their interaction with some angiogenic factors. Our aim was to investigate the role of some angiogenesis-related ECM proteins in the remodeling heart. Methods: We examined cardiac tissue samples from 21 explanted human hearts and 10 non-failing hearts before transplantation. Each specimen was submitted to morphological and biomolecular analysis. Results: We demonstrated a reduced expression of α2-chain laminin mRNA in pathological samples that could play an important role in the progression of cardiac failure by contributing to sarcolemma modifications. Reduced expression of tenascin cytotactin (TN-C) and TN-X in explanted hearts indicated chronic cardiac damage and an impaired capacity to stimulate new vessel development. The observed type IV collagen increase was not related to neoangiogenesis, as reflected by the decreased expression of vascular endothelial growth factor (VEGF)-A and VEGF receptor-2. The inverse correlation between heart dimension and VEGF-A immunopositivity seems particularly interesting. Conclusions: Our findings suggest that ECM reacts strongly to ischemic damage in failing hearts through some important modifications of its protein composition. Nevertheless, this reaction cannot completely restore myocardium structure if it is not supported by adequate neoangiogenesis. The decrease in some ECM proteins related to vessel development has a negative effect on postischemic neoangiogenesis and clinical outcome.

Sphingosine-1-Phosphate Protects Against the Development of Cardiac Remodeling via Sphingosine Kinase 2 and the S1PR2/ERK Pathway

Objective:Cardiac remodeling is a common pathological change in various cardiovascular diseases and can ultimately result in heart failure.Thus,there is an urgent need for more effective strategies to aid in cardiac protection.Our previous work found that sphingosine-1-phosphate(S1P)could ameliorate cardiac hypertrophy.In this study,we aimed to investigate whether S1P could prevent cardiac fibrosis and the associated mechanisms in cardiac remodeling.Methods:Eight-week-old male C57BL/6 mice were randomly divided into a sham,transverse aortic constriction(TAC)or a TAC+S1P treatment group.Results:We found that S1P treatment improved cardiac function in TAC mice and that the cardiac fibrosis ratio in the TAC+S1P group was significantly lower and was accompanied by a decrease inα-smooth muscle actin(α-SMA)and collagen type I(COL I)expression compared with the TAC group.We also found that one of the key S1P enzymes,sphingosine kinase 2(SphK2),which was mainly distributed in cytoblasts,was downregulated in the cardiac remodeling case and recovered after S1P treatment in vivo and in vitro.In addition,our in vitro results showed that S1P treatment activated extracellular regulated protein kinases(ERK)phosphorylation mainly through the S1P receptor 2(S1PR2)and spurred p-ERK transposition from the cytoplasm to cytoblast in H9c2 cells exposed to phenylephrine.Conclusion:These findings suggest that SphK2 and the S1PR2/ERK pathway may participate in the anti-remodeling effect of S1P on the heart.This work therefore uncovers a novel potential therapy for the prevention of cardiac remodeling.

Effect of Different Styles of Coronary Heart Disease and Its Risk Factors on Cardiac Remodeling and Dysfunction

Objectives To evaluate the effect of different styles of coronary heart disease （CHD）, different regions of acute myocardial infarction （AMI）, its risk factors and branches of coronary stenosis on left ventricular remodeling and dysfunction by applying echocardiography. Methods 251 patients with CHD and 96 patients without CHD （NoCHD） were verified by selective coronary angiography. CHD patients were divided into stable angina pectoris （SAP） 26, unstable angina pectoris（UAP） 53, acute myocardial infarction （AMI） 140 and old myocardial infarction （OMI） 30 based on clinical situation, cTnT, cardiac enzyme and ECG. AMI patients were further divided into subgroups including acute anterior myocardial infarct （Aa,n = 53）, acute inferior myocardial infarction （Ai, n=54） and Aa＋Ai （n=33） based on ECG. Cardiac parameters： end-diastolic interventricular septum thickness（IVSd）, end-diastolic left ventricular internal diameter （LVd）, left ventricular mass （LM）, end-diastolic left ventricular volume （EDV）, end-systolic left ventricular volume （ESV） and left ventricular ejection fraction（LVEF） were measured by ACUSON 128XP/10 echocardiography. Multiples linear regression analyses were performed to test statistical associations between LVEF and the involved branches of coronary stenosis, blood pressure, lipids, glucose and etc after onset of myocardial infarction. Results EDV and ESV were increased and LVEF decreased on patients with AMI,OMI and UAP （P〈0.05-0.0001）. LM was mainly increased in patients with OMI （P〈0.01） and LVd was mainly enlarged in patients with AMI. EF was significantly decreased and EDV, ESV, LM and LVd were remarkably increased in AMI patients with Aa and Aa＋Ai. With the multiple linear regression analyses by SPSS software, we found that LVEF was negatively correlated to the involved branches of coronary stenosis as well as to systolic blood pressure after onset of myocardial infarction while there was no significant correlation between LVEF and other factors. LVEF was significantly decreased, and LVd and LM increased in AMI patients with antecedent hypertension, compared to patients without hypertension （P〈0.001）. Conclusions Effects of different styles of CHD and different regions of AMI on left ventricular remodeling and cardiac function are different. Myocardial infarction, especially Aa and Aa＋Ai, is one of the most important causes of left ventricular remodeling and cardiac dysfunction. Multiple vessel stenosis and systolic blood pressure at the onset of myocardial infarction reduce LVEF in AMI patients. Antecedent hypertension may accelerate the effect of AMI on cardiac remodeling and dysfunction. Therefore primary and secondary preventions of CHD are critical for protecting heart from remodeling and dysfunction.

Effect of the adjuvant milrinone therapy on cardiac function, myocardial remodeling and RAAS system activity in patients with chronic heart failure

Objective:To explore the effect of the adjuvant milrinone therapy on cardiac function, myocardial remodeling and RAAS system activity in patients with chronic heart failure. Methods: A total of 110 patients with chronic heart failure who were treated in the hospital between January 2015 and January 2017 were divided into control group (n=55) and observation group (n=55) by random number table method. Control group received conventional therapy for chronic heart failure, and the observation group received milrinone on the basis of conventional therapy. The differences in ultrasound cardiac function and myocardial remodeling index levels as well as serum RAAS index contents were compared between the two groups before and after treatment.Results: Before treatment, the differences in ultrasound cardiac function and myocardial remodeling index levels as well as serum RAAS index contents were not statistically significant between the two groups. After treatment, CO and SV levels of both groups of patients were significantly higher than those before treatment while LADd, LVEDd, LVPWT, IVST and LVMI levels as well as serum PRA, AngⅡ and ALD contents were significantly lower than those before treatment, and CO and SV levels of observation group were significantly higher than those of control group while LADd, LVEDd, LVPWT, IVST and LVMI levels as well as serum PRA, AngⅡ and ALD contents were significantly lower than those of control group.Conclusion: Adjuvant milrinone therapy can effectively enhance the cardiac function, inhibit the myocardial remodeling and decrease the RAAS system activity in patients with chronic heart failure.

Effects of Long-term Right Ventricular Apical Pacing on Left Ventricular Remodeling and Cardiac Function

Objective: To investigate the impacts of long-term right ventricular apical pacing on the ventricular remodeling and cardiac functions of patients with high-grade and third-degree atrioventricular blockage with normal heart structures and cardiac functions. In addition, we provide many evidences for choosing an optimal electrode implantation site.Methods: Study participants included patients who were admitted for pacemaker replacements and revisited for examinations of implanted pacemakers at outpatient. Pacemakers were implanted to treat high-grade and third-degree atrioventricular blockage. At the time of pacemaker implantation, patients had normal cardiac functions and showed no serious heart diseases or cardiac dilatation. The durations from the implantation to follow-up were more than 5 years. The pacing rate was higher than 80%. Patients with a left ventricular ejection fraction (LVEF) < 50% and a left ventricular end-diastolic diameter (LVEDD) > 55 mm were excluded. Ventricular remodeling was defined as follows:increase of LVEDD by 10% and a reduction of LVEF by 25% for five years after implantation. Cardiac functions were evaluated according to New York Heart Association (NYHA) classification.Results:A total of 82 patients with a mean age of (66.97±13.19) years (range, 12 to 91 years old),among which 39 male and 43 female were enrolled in this study. The average duration between two assessments was 8.7 years (104.4 months). Before pacemaker implantation, the average left atrial diameter (LA), LVEDD and LVEF were 37.0 mm, 50.23 mm and 64.87%, respectively. After the implantation, these values were 39.39 mm (P=0.000163), 50.82 mm (P=0.177842) and 60.50% (P=0.000104), respectively. Four patients (4.87%) had ventricular remodeling with deteriorations of cardiac function, three of which had anterior wall myocardial infarction after implantation and one had type II diabetes. Clinical symptoms of heart failure were not found among the patients who did not exhibit ventricular remodeling. Conclusion: Through a long-period follow-up study, we found that long-term right ventricular apical pacing in patients with normal heart structure and cardiac function would not generally cause ventricular remodeling and clinical deteriorations of cardiac function. Right ventricular apical is a safe and effective site for pacing electrode wire implantation.

Transient induction of actin cytoskeletal remodeling associated with dedifferentiation,proliferation,and redifferentiation stimulates cardiac regeneration

The formation of new and functional cardiomyocytes requires a 3-step process:dedifferentiation,proliferation,and redifferentiation,but the critical genes required for efficient dedifferentiation,proliferation,and redifferentiation remain unknown.In our study,a circular trajectory using single-nucleus RNA sequencing of the pericentriolar material 1 positive(PCM1^(+))cardiomyocyte nuclei from hearts 1 and 3 days after surgery-induced myocardial infarction(MI)on postnatal Day 1 was reconstructed and demonstrated that actin remodeling contributed to the dedifferentiation,proliferation,and redifferentiation of cardiomyocytes after injury.We identified four top actin-remodeling regulators,namely Tmsb4x,Tmsb10,Dmd,and Ctnna3,which we collectively referred to as 2D2P.Transiently expressed changes of 2D2P,using a polycistronic non-integrating lentivirus driven by Tnnt2(cardiac-specific troponin T)promoters(Tnnt2-2D2P-NIL),efficiently induced transiently proliferative activation and actin remodeling in postnatal Day 7 cardiomyocytes and adult hearts.Furthermore,the intramyocardial delivery of Tnnt2-2D2P-NIL resulted in a sustained improvement in cardiac function without ventricular dilatation,thickened septum,or fatal arrhythmia for at least 4 months.In conclusion,this study highlights the importance of actin remodeling in cardiac regeneration and provides a foundation for new gene-cocktail-therapy approaches to improve cardiac repair and treat heart failure using a novel transient and cardiomyocyte-specific viral construct.