Effects of allitridum on the transient outward potassium current in rats with heart failure

Objective To study the effect of allitridum on the transient outward potassium current (I_to) of ventricular myocytes in heart failure (HF). Methods The dual enzymatic method was used to separate single ventricular myocytes from Sprague Dawley rats. Patch-clamping was used to record I_to and analyze the effect of allitridum on the current. Results The I_to current had a significant decrease in the HF group, compared with the control group. The density of I_to in the HF group was increased after treatment of allitridum (30 μmol/L). The peak current densities of I_to were enhanced in the HF group from 6.01 ± 0.30 pA/pF to 8.41 ± 0.54 pA/pF (P < 0.01) at +50 mV after treatment with allitridum (30 μmol/L). We also determined the effect of allitridum on the gating mechanism of the I_to in the HF group. Conclusions We found that allitridum increased the I_to by accelerating the activation of channels and shortened the time constants of inactivation, and allitridum decreased the remodeling of I_to in ventricular myocytes of rats with HF.     

Role of TGF-β1/Smads pathway in carotid artery remodeling in renovascular hypertensive rats and prevention by Enalapril and Amlodipine

Objective To investigate the role of transforming growth factor-β1 (TGF-β1), Smad2/3 and Smad7 expressions in carotid artery remodeling in renovascular hypertensive rats, and also the therapeutic effect of Enalapril and Amlodipine. Methods The renovascular hypertensive rat (RHR) models with “two-kidney and one-clip” were established, including model group (n = 6), sham-operated group (n = 6), Enalapril group (10 mg/kg per day, n = 6), Amlodipine group (5 mg/kg per day, n = 6) and combination group (Amlodipine 2.5 mg/kg per day + Enalapril 5mg/kg per day, n = 6). The medication were continuous administrated for six weeks. Carotid artery morphological and structural changes in the media were observed by HE staining, Masson staining and immuno histochemical staining. Media thickness (MT), MT and lumen diameter ratio (MT/LD), and the expression levels of media α-smooth muscle actin (α-actin), proliferating cell nuclear antigen (PCNA), TGF-β1, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in carotid arteries were measured. Results The media of carotid arteries in RHR model group was significantly thickened, the volume of smooth muscle cell was increased, and the array was in disorder; MT, MT/LD, the proliferation index of smooth muscle cell and collagen fiber area percentage of carotid arteries in the model group were significantly higher than those in the sham-operated group (P < 0.01). Compared to sham-operated group, the model group had significantly higher expressions of TGF-β1 and p-Smad2/3 (P < 0.05) and lower Smad7 expression. Both Enalapril and Amlodipine improved smooth muscle hypertrophy and collagen deposition, reduced RHR carotid MT, MT/LD, proliferation index of smooth muscle cell, collagen fiber area percentage and the expressions of TGF-β1 and p-Smad2/3 (P < 0.05), increased Smad7 expression (P < 0.05). Moreover, the combination treatment of Enalapril and Amlodipine had significantly better effects than single Amlodipine group (P < 0.05), but not single Enalapril group. Conclusions TGF-β1/Smads pathway may participate in the mechanism of carotid artery remodeling in RHR; the role of Amlodipine and Enalapril in inversing carotid artery remodeling may be related to the change of TGF-β1/Smads pathway, the combination treatment of Amlodipine and Enalapril had better effects than single administration of Amlodipine.     

Cardioprotective effects of Guanxinshutong (GXST) against myocardial ischemia/ reperfusion injury in rats

Background The protective effects against reperfusion injury of cardioprotective drugs have recently been evaluated and found to be inadequate. Guanxinshutong (GXST), a combination of the traditional herb and Mongolian medicine, is effective and safe in treating angina pectoris in clinical trials. We assess the cardioprotective effects of GXST against myocardial ischemia and reperfusion (MI/R) injury in rats and explore its possible mechanism. Methods Forty-five male Sprague Dawley rats were randomized into three groups: non-MI/R group (Sham, n = 15), MI/R group treated with vehicle (Control, n = 15) and MI/R group treated with GXST (Drug, n = 15). MI/R was induced by ligation of the left anterior descending coronary artery (LAD) for 30 minutes, followed by 2/24 hour reperfusion in the Control and Drug groups. In the Sham group, the LAD was exposed without occlusion. GXST powder (in the Drug group) or saline (in the Control and Sham groups) were administered via direct gastric gavage from 7 day prior to surgery. Blood samples were collected from the carotid artery (10 rats each group) after 2 hours of reperfusion, to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) using enzyme-linked immunosorbent assays. The animals were then sacrificed and the hearts were harvested for histopathology and western blot analysis. Infarct size was measured in the remaining five rats in each group after 24 hours reperfusion. Results GXST significantly decreased levels of TNF-α, IL-1β, IL-6, ICAM-1, apoptosis index (AI) and infarct size. GXST also obviously inhibited nuclear factor kappa B (NF-κB) activity when compared with the Control group (all P < 0.05). Conclusions GXST is effective in protecting the myocardium against MI/R injury in rats. Its possible cardioprotective mechanism involves inhibition of the inflammatory response and apoptosis following MI/R injury.     

Effect and mechanism of Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia through connexin43(cx43)

Objective: To explore the effect and mechanism of angiotensin Ⅱ receptor blockers-Irbesartan on occurrence of ventricular arrhythmias in rats with myocardial ischemia. Methods: Rats with embryonic cardiomyocytes-H9c2 were randomly divided into control group, ischemia group, Irbesartan group and Irbesartan+ischemia group. The cell viability of rats in each group was tested using MTT. Real-time PCR was employed to detect the expression of connexin43(Cx43) mR NA and western blot to detect the expression of Cx43 and phosphorylated Cx43. SD rats were randomly divided into the sham-operation group(SO), myocardial infarction group(MI), Irbesartan group and MI+ Irbesartan group, with 10 rats in each group. HE staining was employed to observe the change in the pathomorphology of left ventricular tissue and TUNEL method to analyze the cell apoptosis in the tissue. The immunofluorescence was adopted to observe the expression and distribution of Cx43 in the left ventricular myocardium and study the change in the expression of Cx43 in the cardiac muscular tissue at mR NA and protein level. Results: The intervention of Irbesartan in the condition of ischemia indicated the significant decrease in the number of necrotic cells. The expression of Cx43 was significantly decreased under the culture of ischemia(P0.05), but in the presence of Irbesartan, the expression of Cx43 was increased compared with the ischemia group(P0.01). The results of WB assay showed the similar trend of change at mRNA level. There was the significant difference in the score of ventricular arerythmia between MI group and SO group(P0.01). The incidence of ventricular tachycardia or ventricular fibrillation was significantly increased compared with the one in SO group(P0.05). There was the significant difference in the overall score between MI+Irbesartan group and MI group(P0.05). The expression of Cx43 in the cardiac muscular tissue in MI group was significantly decreased(P0.01 vs SO group). But the expression of Cx43 was increased after the treatment with Irbesartan. Conclusions: Irbesartan can inhibit the injury of H9c2 cardiomyocytes and the decreased expression of Cx43 that are induced by the ischemic myocardial infarction. Irbesartan can also improve the reconstruction of Cx43 in rats with ischemic myocardium to inhibit the myocardial infarction-induced arrhythmias.     

Effects of Angiotensin Ⅱ on Expression of the Gap Junction Channel Protein Connexin 43 in Neonatal Rat Ventricular Myocytes

To study the effects of angiotensin Ⅱ,as a mediator of cardiac hypertrophy,on expression of connexin 43 (Cx43) in cultured neonatal rat ventricular myocytes and correlation of expression of Cx43 and cardiomyocyte hypertrophy.Methods Cardiomyocytes were isolated from newborn SD rats.Angiotensin Ⅱ was added into the media to induce myocyte hypertrophy.Cultures were exposed to 10 ～6 mol/L angiotensin Ⅱ for 72 h,Cx43 expression was characterized by RT-PCR and Immunofluorescence methods.Results Immunofluorescence analysis revealed decreased Cx43 immunoreactivity in cells treated for 72 h with angiotensin Ⅱ.RT-PCR analysis demonstrated there was an obvious decrease of Cx43 mRNA level in cells exposed to angiotensin Ⅱ for 72 h.The changes of expression of connexin 43 were related to its entrance into S phase of the cell cycle.Cultured neonatal rat cardiomyocytes were exposed for 72 h to increase concentrations of angiotensin Ⅱ ( 1.0 × 10-9 ～ 1.0 × 10-6mol/L),resulting in significantly decreased Cx43 expression.Conclusions Angiotensin Ⅱ leads to a concentration-dependent decrease in Cx43 protein in cultured neonatal rat ventricular myocytes by decreasing Cx43 mRNA synthesis.Signal transduction pathways activated by angiotensin Ⅱ under pathophysiologic conditions of cardiac hypertrophy could initiate remodeling of gap junctions.     

Effects and mechanism of different doses of Xinfuli Granule on ventricular remodeling and myocardial fibrosis after acute myocardial infarction in rats

Background Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinese medicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG on ventricular reconstruction in rats with acute myocardial infarction (AMI). Methods Sprague-Dawley rats were subjected to left anterior descending branch ligation. The rats that survived 24 h were randomly assigned to 5 groups: medium-dose of XG group (MI+XGM), high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM). Fourteen rats underwent identical surgical procedures without artery ligation, serving as sham controls. At 28 days, left ventricular weight to body weight (LVW/BW) and heart weight to body weight (HW/BW) were calculated; left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS), left ventricular internal diameter at systole (LVIDS) were measured by ultrasound; HE staining, Masson staining, and Sirius red staining were used to assess the myocardial pathological and physiological changes as well as myocardial fibrosis area and non-infarct zone I/III collagen ratio. Expression of Smad3 were detected and analyzed by Western blot, immunohistochemistry and immunofluorescence. P-Smad3, Smad2 and Smad7 in the TGF-β/Smads signaling pathway were also analyzed by Western blot. Results The LVIDS (P < 0.01), HW/BW (P < 0.05), type I/III collagen ratio (P < 0.01) and myocardial collagen (P < 0.01) decreased significantly while the LVW/BW, LVFS (P < 0.05) increased significantly in MI+XGM group as compared with those in other groups. The expression of key signal molecules of the TGF-β/Smads signaling pathway, including Smad3, P-Smad3 and Smad2 protein were decreased while the expression of Smad7 increased in both XG and carvedilol treatment groups as compared to those of the MI group (all P < 0.01). Immunohistochemistry and immunofluorescence further confirmed the down-regulated Smad3 expression. Conclusion XG can improve ventricular reconstruction and inhibit myocardial fibrosis in rats with AMI by regulating TGF-β/Smads signaling pathway.     

Effects of Angiotensin II on Expression of the Gap Junction Channel Protein Connexin 43 in Neonatal Rat Ventricular Myocytes

Objectives To study the effects of angiotensin II, as a mediator of cardiac hypertrophy, on expression of connexin 43 (Cx43) in cultured neonatal rat ventricular myocytes and correlation of expression of Cx43 and cardiomyocyte hypertrophy. Methods Cardiomyocytes were isolated from newborn SD rats. Angiotensin II was added into the media to induce myocyte hypertrophy. Cultures were exposed to 10～6 mol/L angiotensin II for 72 h, Cx43 expression was characterized by RT-PCR and Immunofluorescence methods. Results Immunofluorescence analysis revealed decreased Cx43 immunoreactivity in cells treated for 72 h with angiotensin II. RT-PCR analysis demonstrated there was an obvious decrease of Cx43 mRNA level in cells exposed to angiotensin II for 72 h. The changes of expression of connexin 43 were related to its entrance into S phase of the cell cycle. Cultured neonatal rat cardiomyocytes were exposed for 72 h to increase concentrations of angiotensin II (1.0×10-9～1.0×10-6mol/L), resulting in significantly decreased Cx43 expression. Conclusions Angiotensin II leads to a concentration-dependent decrease in Cx43 protein in cultured neonatal rat ventricular myocytes by decreasing Cx43 mRNA synthesis. Signal transduction pathways activated by angiotensin II under pathophysiologic conditions of cardiac hypertrophy could initiate remodeling of gap junctions.     

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

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

Combination of thrombus aspiration, high-dose statin, adenosine and platelet membrane glycoprotein Ⅱb/Ⅲa receptor antagonist reduce the incidence of no-reflow after primary percutaneous coronary intervention in patients with ST-segment elevation acut

Background No-reflow is associated with an adverse outcome and higher mortality in patients with ST-segment elevation acute my-ocardial infarction (STEMI) who undergo percutaneous coronary intervention (PCI) and is considered a dynamic process characterized by multiple pathogenetic components. The aim of this study was to investigate the effectiveness of a combination therapy for the prevention of no-reflow in patient with acute myocardial infarction (AMI) undergoing primary PCI. Methods A total of 621 patients with STEMI who underwent emergency primary PCI were enrolled in this study. Patients with high risk of no-reflow (no-flow score ≥ 10, by using a no-flow risk prediction model, n = 216) were randomly divided into a controlled group (n = 108) and a combination therapy group (n = 108). Patients in the controlled group received conventional treatment, while patients in combination therapy group received high-dose (80 mg) atorvastatin pre-treatment, intracoronary administration of adenosine (140 μg/min per kilogram) during PCI procedure, platelet membrane glycoprotein Ⅱb/Ⅲa receptor antagonist (tirofiban, 10μg/kg bolus followed by 0.15 μg/kg per minute) and thrombus aspiration. Myocardial contrast echocardiography (MCE; SonoVue^?; Bracco) was performed to assess the myocardial perfusion 72 h after PCI. Major adverse cardiac events (MACE) were followed up for six months. Results Incidence of no-reflow in combination therapy group was 2.8%, which was similar to that in low risk group 2.7% and was significantly lower than that in control group (35.2%, P < 0.01). The myocardial perfusion (A × β) values were higher in combination therapy group than that in control group 72 h after PCI. After 6 months, there were six (6.3%) MACE events (one death, two non-fatal MIs and three revascularizations) in combination therapy group and 12 (13.2%) (four deaths, three non-fatal MIs and five revascularizations, P < 0.05) in control group. Conclusions Combination of thrombus aspiration, high-dose statin pre-treatment, intracoronary administration of adenosine during PCI procedure and platelet membrane glycoprotein Ⅱb/Ⅲa receptor antagonist reduce the incidence of no-reflow after primary PCI in patients with acute myocardial infarction who are at high risk of no-reflow.     

Effects of a nurse-led heart failure clinic on hospital readmission and mortality in Hong Kong

Background Heart failure (HF) is a physically and socially debilitating disease that carries the burden of hospital re-admission and mortality. As an aging society, Hong Kong urgently needs to find ways to reduce the hospital readmission of HF patients. This study evaluates the effects of a nurse-led HF clinic on the hospital readmission and mortality rates among older HF patients in Hong Kong. Methods This study is a retrospective data analysis that compares HF patient in a nurse-led HF clinic in Hong Kong compared with HF patients who did not attend the clinic. The nurses of this clinic provide education on lifestyle modification and symptom monitoring, as well as titrate the medications and measure biochemical markers by following established protocols. This analysis used the socio-demographic and clinical data of HF patients who were aged ≥ 65 years old and stayed in the clinic over a six-month period. Results The data of a total of 78 HF patients were included in this data analysis. The mean age of the patients was 77.38 ± 6.80 years. Approximately half of the HF patients were male (51.3%), almost half were smokers (46.2%), and the majority received ≤ six years of formal education. Most of the HF patients (87.2%) belonged to classes II and III of the New York Heart Association Functional Classification, with a mean ejection fraction of 47.15 ± 20.31 mL. The HF patients who attended the clinic (n = 38, 75.13 ± 5.89 yrs) were significantly younger than those who did not attend the clinic (n = 40, 79.53 ± 6.96 yrs) (P = 0.04), and had lower recorded blood pressure. No other statistically significant difference existed between the socio-demographic and clinical characteristics of the two groups. The HF patients who did not attend the nurse-led HF clinic demonstrated a significantly higher risk of hospital readmission [odd ratio (OR): 7.40; P < 0.01] than those who attended after adjusting for the effect of age and blood pressure. In addition, HF patients who attended the clinic had lower mortality (n = 4) than those who did not attend (n = 14). However, such a difference did not reach statistical significance when the effects of age and blood pressure were adjusted. A significant reduction in systolic blood pressure [F (2, 94) = 3.39, P = 0.04] and diastolic blood pressure [F (2, 94) = 8.48, P < 0.01] was observed among the HF patients who attended the clinic during the six-month period. Conclusions The finding of this study suggests the important role of nurse-led HF clinics in reducing healthcare burden and improving patient outcomes among HF patients in Hong Kong.     

Rosuvastatin inhibits the smooth muscle cell proliferation by targeting TNFα mediated Rho kinase pathway

Objective To investigate whether Tumor Necrosis Factor-alpha (TNFα) is capable of activating Rho kinase pathway which leads to smooth muscle cell proliferation and the intervention function of Rosuvastatin, and clarify the mechanism and intervention manner of anti-atherosclerosis by Rosuvastatin. Methods Wistar neonate rat smooth muscle cells were cultured, and the activity of cell proliferation was determined by methyl thiazolyl tetrazolium (MTT). The expression of Rho kinase genes after the stimulation of TNFα was evaluated by RT-PCR. Western blot method was used to measure the protein expression of proliferating cell nuclear antigen (PCNA) after TNFα stimulation and Rosuvastatin intervention in smooth muscle cell. Results The TNFα stimulation significantly enhanced the expression of Rho kinase and increased the expression of PCNA protein in smooth muscle cells (P < 0.05). These effects were positively correlated with prolonged treatment whereas additional Rosuvastatin administration inhibited the above-mentioned effects (P < 0.05). Conclusions The activation of TNFα mediated Rho kinase signaling pathway can significantly promote smooth muscle cell proliferation, and Rosuvastatin can not only inhibit this pathway but also the induced proliferation.     

Effects of Ang Ⅱ perfusion on transmural heterogeneous of Cx43 in acute myocardial ischemia reperfusion

Objective:To observe the effects of angiotensin Ⅱ(Ang Ⅱ) pefusion on transmural heterogeneity of Cx43 expression in the rabbit model with acute myocardial ischemia reperfusion(MIR),and investigate the role of rennin-angiotensin system in malignant ventricular arrhythmia induced by MIR.Methods:Twenty rabbits were randomly divided into MIR group(n=10) and Ang Ⅱ group(n=10).MIR model was produced with traditional ligation and opening of the anterior descending coronary artery in all animal.The hearts in vitro in the MIR group and the Ang Ⅱ group were perfused with simply improved Tyrode's solution and containing Ang Ⅱ Tyrode's solution respectively.90%monophasic action potential repolarization duration,transmural dispersion of repolarization.Cx43 protein(Cx43-pro) and mRNA(Cx43-Cq) expression in subepicardial,midmyocardial and subendocardial myocardium were measured in both groups.The greatest differences of Cx43-pro and Cx43-Cq among three myocardial layers were calculated and shown with △Cx43-pro and △Cx43-Cq respectively.Results:After Ang Ⅱ perfusion,90%monophasic action potential repolarization duration among three myocardial layer were significantly prolonged(P 0.05 and P 0.01),and transmural dispersion of repolarization also significantly increased compared with the MIR group(P 0.05).Compare with the MIR group,three myocardial Cx43-pro and Cx43-Cq expression in the Ang Ⅱ group were significantly decreased(P 0.05 and P 0.01).but△Cx43-pro and △Cx43-Cq were significant increased.Conclusions:Renin-angiotensin system increases transmural heterogeneity of Cx43 expression in the rabbit model with MIR by Ang Ⅱ,and enlarge transmural dispersion of repolarization among three myocardial layers of left ventricular which induces malignant ventricular arrhythmia.     

Effect of β blockers on β_3-adrenoceptor mRNA Expression in the Rats with Chronic Heart Failure

Objectives To investigate the changes of β3-adrenoceptor (β3-AR) mRNA expression in the rats with chronic heart failure (CHF), and to explore the effect of β blockers (βBs) on β3 mRNA expression. Methods Thirty-four rats were randomly divided into Sham group (n = 10) and heart failure group (n = 24). Rat model was established by aortic constriction. The survival rats in heart failure group were divided into heart failure control group (HF group, n = 6), metoprolol group (MET group, n = 8) and carvedilol group (CAR group, n = 8) three months after operation. Metoprolol tartarte was started orally with 12 mg·kg-1·d-1, carvedilol with 6 mg·kg-1·d-1, isometric saline was started in HF group. After three months of drug therapy, measurement of hemodynamics, index of ventricular mass, the level of β3-AR mRNA expression were performed. Results Compared with Sham group, left ventricular end systolic pressure (LVESP), and the absolute values of maximal rate of rise and fall ( ± dp/dtmax) of left ventricular pressure were all significantly decreased (P < 0.01), left ventricular end diastolic pressure (LVEDP) was significantly increased in HF group (P < 0.01). The hemodynamic parameters were improved by βBs, and carvedilol was more effective than metoprolol (P < 0.01). The index of ventricular mass was higher in HF group than MET group, CAR group and Sham group (P < 0.01). βBs significantly decreased the index of left ventricular mass (LVMI), and Carvedilol was more effective than metoprolol (P < 0.01). The index of right ventricular mass (RVMI) did not change in MET group (P > 0.05), but significant decrease could be seen in CAR group (P < 0.01). The level of β3-AR expression in left ventricle was greater than that in right ventricle whether in the failing heart or in the non-failing heart. Compared with Sham group, the level of β3-AR mRNA expression was significantly increased in HF group (P < 0.01). The levels of β3-AR mRNA expression showed a remarkable decrease in CAR group(P < 0.01), but was not seen in MET group. Conclusions The β3-AR expression level remarkably increases in the rat's left and right failing ventricles. Carvedilol is more effective on improving hemodynamics and attenuating ventricular remodeling than metoprolol in the rats with CHF. Carvedilol rather than metoprolol downregulates β3-AR expression in the rat's failing ventricles. The beneficial effect of carvedilol in CHF maybe partly due to the downregulation of β3-AR expression in the failing heart.     

缝隙连接蛋白43在老年大鼠缺血性室性心律失常中的作用

Objective To investigate the expression of connexin43 ( Cx43 ) and effect of vagal nerve stimulation (VNS) on ventricular tachyarrhythmias during acute myocardial ischemia( MI )in aged rats. Methods Male Sprague-Dawley rats[Adult group ( ≤ 4 months) and Aged group ( ≥24 months)]:MI (n = 15 ):ligated left anterior descending coronary for 30 minutes; MI-vagal nerve stimulation(VNS) ( n = 15 ); MI-VNS-atropine (0. 5 mg/kg, n = 13 ); MI-VNS-carbenoxolone ( 10 mg/kg, n = 11 ); sham operation (SO, n = 10):without coronary ligation. Ventricular arrhythmias were monitored by an electrocardiogram. Cx43 protein expression was analyzed by Western blot. Results During the 30 minutes ligation,incidences of ventricular tachycardia (VT) and ventricular fibrillation(VF) in aged rats increased significantly compared to those of adult rats ( P ＜ 0. 05 ). VNS did not affect the occurrence of VT and VF ( both P ＞ 0.05 ); however, VNS suppressed the occurrence of irreversible VF ( P ＜ 0. 05 ); both atropine and carbenoxolone ( a gap junction inhibitor) could abolish the effect of VNS on ischemia-induced irreversible VF ( both P ＜0. 05). Ischemia did not result in changes of total Cx43 amount in adult and aged rats compared to that of SO group,respectively. The amount of nonphosphorylated Cx43 was increased markedly in adult and aged rats compared to that of SO group,respectively.Cx43 dephosphorylation induced by ischemia was significantly suppressed by VNS in adult and aged rats( P ＜0. 05 ). However,the amount of total Cx43 of SO group in aged rats was significantly decreased by 50% compared to that of SO group in adult rats ( P ＜ 0. 05 ). Conclusion The present study suggested that the incidence of ischemia-induced ventricular tachyarrhythmias increased markedly and the anti-arrhythmic effect of VNS was decreased significantly in aged rats, which may be associated with reduction of Cx43 protein of ventricle in aged rats.     

Protective effect of heme oxygenase-1 on Wistar rats with heart failure through the inhibition of inflammation and amelioration of intestinal microcirculation

Background Myocardial infarction (MI) has likely contributed to the increased prevalence of heart failure (HF). As a result of reduced cardiac function, splanchnic blood flow decreases, causing ischemia in villi and damage to the intestinal barrier. The induction of heme oxygenase-1 (HO-1) could prevent, or lessen the effects of stress and inflammation. Thus, the effect and mechanism thereof of HO-1 on the intestines of rats with HF was investigated. Methods Male Wistar rats with heart failure through ligation of the left coronary artery were identified with an left ventricular ejection fraction (LvEF) of < 45% through echocardiography and then divided into various experimental groups based on the type of peritoneal injection they received [MI: saline; MI + Cobalt protoporphyrin (CoPP): CoPP solution; and MI + Tin mesoporphyrin IX dichloride (SnMP): SnMP solution]. The control group was comprised of rats without coronary ligation. Echocardiography was performed before ligation for a baseline and eight weeks after ligation in order to evaluate the cardiac function of the rats. The bacterial translocation (BT) incidence, mesenteric microcirculation, amount of endotoxins (ET) in the vein serum, ileum levels of HO-1, carbon oxide (CO), nitric oxide (NO), interleukin (IL)-10, tumour necrosis factor-α (TNF-α), and the ileum morphology were determined eight weeks after the operation. Results The rats receiving MI + CoPP injections exhibited a recovery in cardiac function, an amelioration of mesenteric microcirculation and change in morphology, a lower BT incidence, a reduction in serum and ileac NO and TNF-α levels, and an elevation in ileac HO-1, CO, and interleukin-10 (IL-10) levels compared to the MI (P < 0.05) group. The rats that received the MI + SnMP injections exhibited results inverse to the MI (P < 0.05) group. Conclusions HO-1 exerted a protective effect on the intestines of rats with HF by inhibiting the inflammation and amelioration of microcirculation through the CO pathway. This protective effect could be independent from the recovery of cardiac function.     

缝隙连接蛋白43在老年大鼠缺血性室性心律失常中的作用

Objective To investigate the expression of connexin43 ( Cx43 ) and effect of vagal nerve stimulation (VNS) on ventricular tachyarrhythmias during acute myocardial ischemia( MI )in aged rats. Methods Male Sprague-Dawley rats[Adult group ( ≤ 4 months) and Aged group ( ≥24 months)]:MI (n = 15 ):ligated left anterior descending coronary for 30 minutes; MI-vagal nerve stimulation(VNS) ( n = 15 ); MI-VNS-atropine (0. 5 mg/kg, n = 13 ); MI-VNS-carbenoxolone ( 10 mg/kg, n = 11 ); sham operation (SO, n = 10):without coronary ligation. Ventricular arrhythmias were monitored by an electrocardiogram. Cx43 protein expression was analyzed by Western blot. Results During the 30 minutes ligation,incidences of ventricular tachycardia (VT) and ventricular fibrillation(VF) in aged rats increased significantly compared to those of adult rats ( P ＜ 0. 05 ). VNS did not affect the occurrence of VT and VF ( both P ＞ 0.05 ); however, VNS suppressed the occurrence of irreversible VF ( P ＜ 0. 05 ); both atropine and carbenoxolone ( a gap junction inhibitor) could abolish the effect of VNS on ischemia-induced irreversible VF ( both P ＜0. 05). Ischemia did not result in changes of total Cx43 amount in adult and aged rats compared to that of SO group,respectively. The amount of nonphosphorylated Cx43 was increased markedly in adult and aged rats compared to that of SO group,respectively.Cx43 dephosphorylation induced by ischemia was significantly suppressed by VNS in adult and aged rats( P ＜0. 05 ). However,the amount of total Cx43 of SO group in aged rats was significantly decreased by 50% compared to that of SO group in adult rats ( P ＜ 0. 05 ). Conclusion The present study suggested that the incidence of ischemia-induced ventricular tachyarrhythmias increased markedly and the anti-arrhythmic effect of VNS was decreased significantly in aged rats, which may be associated with reduction of Cx43 protein of ventricle in aged rats.     

Effect of coronary artery revascularization on in-hospital outcomes and long-term prognoses in acute myocardial infarction patients with prior is-chemic stroke

Objective To investigate whether coronary artery revascularization therapies (CART), including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), can improve the in-hospital and long-term outcomes for acute myocardial infarction (AMI) patients with prior ischemic stroke (IS). Methods A total of 387 AMI patients with prior IS were enrolled consecutively from January 15, 2005 to December 24, 2011 in this cohort study. All patients were categorized into the CART group (n = 204) or the conservative medications (CM) group (n = 183). In-hospital cardiocerebral events and long-term mortality of the two groups after an average follow-up of 36 months were recorded by Kaplan-Meier survival curves and compared by Logistic regression and the Cox regression model. Results The CART patients were younger (66.5 ± 9.7 years vs. 71.7 ± 9.7 years, P < 0.01), had less non-ST segment elevation myocardial infarction (11.8% vs. 20.8%, P = 0.016) and more multiple-vascular coronary lesions (50% vs. 69.4%, P = 0.031). The hospitalization incidence of cardiocerebral events in the CART group was 9.3% while 26.2% in the CM group (P < 0.01). CART significantly reduced the risk of in-hospital cardiocerebral events by 65% [adjusted odds ratio (OR) = 0.35, 95% CI: 0.13–0.92]. By the end of follow-up, 57 cases (41.6%) died in CM group (n = 137) and 24 cases (12.2%) died in CART group (n = 197). Cox regression indicated that CART decreased the long-term mortality by 72% [adjusted hazard ratio (HR) = 0.28, 95% CI: 0.06–0.46], while categorical analysis indicated no significant difference between PCI and CABG. Conclusions CART has a significant effect on improving the in-hospital and long-term prognoses for AMI patients with prior IS.     

Improvement of increased cQTd is associated with heart function in patients with ischemic heart failure

Background Chronic heart failure (CHF) is life-threatening without timely or effective intervention. In this study, we investigated the association between QT dispersion corrected for heart rate (cQTd) and heart function in patients with CHF. Methods From January 2013 to December 2015, we continuously enrolled 240 patients categorized as New York Heart Association functional class (NYHA) III?IV with a left ventricular ejection fraction (LVEF) < 40%. Based on the etiology, the patients were divided into a dilated cardiomyopathy (DCM) group (n = 120) and an ischemic cardiomyopathy (ICM) group (n = 120). Then, based on the cQTd width, the ICM group was divided into two subgroups: a QS group (cQTd ≤ 60 ms, n = 70) and a QL group (cQTd > 60 ms, n = 50). All patients were examined by echocardiography and 12-lead electrocardiography (ECG) at 1, 3, 6, and 12 months after enrollment. Results After one year of optimized medical treatment, patients in both groups showed significant improvement in LVEF and NYHA classification from baseline. However, the cQTd in the ICM group, especially the QL, was significantly shorter than that in the DCM group at each time point. In addition, the cQTd was negatively correlated with LVEF and 6-min walking test and positively correlated with NYHA class in the ICM group. Conclusions The present findings clearly demonstrate that cQTd is a meaningful parameter for assessing heart function in the follow-up of ICM patients.     

Lexipafant fails to improve survival in severe necrotizing pancreatitis in rats

Summary Conclusions. Lexipafant administration fails to improve survival or lessen the disease severity in two experimental models of severe acute pancreatitis. Background. The potent platelet activating factor antagonist Lexipafant has been shown to attenuate the biochemical and histologic changes associated with some animal models of acute pancreatitis, suggesting an important role for this cytokine in its pathogenesis. However, a survival advantage following Lexipafant administration has not been demonstrated. This study evaluates the effect of this platelet activating antagonist on survival in rat models of necrotizing and fulminant hemorrhagic pancreatitis. Methods. Sprague-Dawley rats underwent induction of either acute necrotizing (n=40) or hemorrhagic pancreatitis (n=36) with a time- and pressure-controlled bile duct infusion of 10 mM glycodeoxycholic acid (GDOC) or enterokinase 15 U/mL, in combination with supramaximal cerulein stimulation (5 μg/kg/h). Immediately after pancreatitis induction, rats were randomly divided into three groups and received Lexipafant (1 mg or 10 mg) or saline as a continuous intravenous infusion over 9 h. Twenty-four-hour survival rates were determined and severity of pancreatitis was assessed by pancreatic histology scores. Results. The survival rates for GDOC treated rats were 55% (saline), 50% (1 mg Lexipafant) and 50% (10 mg Lexipafant). As expected, all rats induced with enterokinase and treated with saline died with hemorrhagic pancreatitis within 24 h. The same was true of those treated with high- and low-dose Lexipafant, and there was no difference in survival time. Histology scores did not differ between Lexipafant-treated and control rats in either GDOC or enterokinase rats.