Objective To observe the therapeutic effects of Isosorbide Mononitrate on endothelial function in atherosclerosis in rabbits.Methods Thirty New Zealand white rabbits were randomly divided into three groups:control group,high cholesterol (1.5% Cholesterol+5% cocoa butter) group and Isosorbide Mononitrate (ISMN) group (high cholesterol diet + ISMN 0.5 g·kg-1·d-1,10 rabbits for each group.The extent of atherosclerotic plaque was evaluated by HE staining.The expression of LOX-1 and P-selectin was evaluated by immunohistochemistry staining.The serum total cholesterol (TC) and triglyceride (TG) were measured by a kit.Results The extent of atherosclerotic plaque was significantly lower in ISMN group than that of high cholesterol group.The expression of LOX-1 and P-selectin was lower in ISMN group than those of high cholesterol group.But there was no statistical difference of serum TC and TG level between ISMN group and high cholesterol group.Conclusion The results suggest that ISMN can alleviate the progress of AS by reducing the expression of adhesive molecule,inhibiting inflammatory response and improving endothelial function.

Objective To observe the relations of soluble intercellular adhesion molecules-1(sICAM-1),vascular cell adhesion molecules-1(sVCAM-1)to blood pressure,blood sugar,blood lipid and the influence of rosuvastatin on sICAM-1 and sVCAM-1 in serum of patients with acute coronary syndrome(ACS),to probe into the mechanism of rosuvastatin lowering inflammatory reaction in ACS patients.Methods 112 elderly patients were divided into two groups:36 patients with stable angina pectoris(SAP),76 patients with ACS.The latter group were randomly divided into rosuvastatin and non-rosuvastatin sub-groups.Serum concentrations of sICAM1 and sVCAM-1 in patients with ACS were measured by ELISA at 1,3,5,7,14 day after hospitalization.Moreover,the relations of sICAM-1 and sVCAM-1 to the history of hypertension,diabetes mellitus,dyslipidemia as well as blood pressure,blood sugar,blood lipid were analyzed.Results Serum concentrations of sICAM-1 and sVCAM-1 in elderly patients with ACS were higher than those of SAP group(P0.01).sICAM-1,sVCAM-1 levels in plasma were higher in hypertension,diabetes mellitus,dyslipidemia groups than normal pressure,non-diabetes,normal lipid respectively.Mutivariable analysis showed that sICAM-1,sVCAM-1 levels in plasma were correlated to LDL-C positively(P0.01)but not heart rate,systolic pressure,diastolic pressure,TC,HDL-C,TG,FBG,HbA1C(P0.05).In two sub-groups of ACS group,serum concentrations of sICAM-1 and sVCAM-1 in rosuvastatin group were decreased more significantly than those of the other.Conclusions Endothelium impairment induced by hypertension,diabetes mellitus,dyslipidemia is important factor of elevating sICAM-1,sVCAM-1 levels in plasma;Rosuvastatin may decrease inflammatory reaction and play a pivotal role in early therapy of ACS patients.

Objective To investigate the plasma levels of a disintegrin and metalloprotease(ADAMTS-1) and matrix metalloproteinase(MMPs) in patients with coronary heart disease(CHD)complicated with chronic heart failure(CHF).Methods A total of 89 patients with angiographical CHD were recruited,of which 68 patients complicated with CHF were selected as the CHF group,NYHA lassification was Ⅱ~Ⅳ,and another 21 patients without CHF were served as the control group.Plasma ADAMTs-1,MMP-2,MMP-9 and N-terminal fragment of the pro-peptide of brain natriuretic peptide(NT-proBNP) were determined by ELISA method.Left ventricular end-diastolic dimension(LVEDd) and left ventricular ejection fraction(LVEF) were measured with cardiac color ultrasonography.Severity of coronary artery lesion was evaluated by SYNTAX integral method.The correlations of ADAMTs-1,MMP-2,MMP-9,NT-proBNP,LVEDd,LVEF,SYNTAX score were analyzed.Results Plasma NT-proBNP,MMP-2 and MMP-9 levels in HF group were higher than those in the control group(all P0.05),and evidently increased with the increased severity of heart failure(P0.05).Plasma MMP-2 and MMP-9 levels were positively related with NT-proBNP and LVEDd,and negatively related with LVEF(P0.01).There was no significant difference in plasma ADAMTs-1 level between the CHF group and the control group,but plasma ADAMTs-1 level was positively related with the SYNTAX score(P0.01).Conclusions Plasma MMP-2 and MMP-9 may be involved in ventricular remolding of patients with CHD complicated with CHF.Measuring plasma MMP-2 and MMP-9 concentration of patients with CHD complicated with CHF may be helpful to diagnose and evaluate the severity of heart failure.ADAMTs-1 may be a indicator of coronary artery lesions.

目的 观察急性心肌梗死(AMI)患者急性期血白细胞计数与肌钙蛋白、心律失常的相互关系,探讨血白细胞计数对AMI心律失常发生的预测价值.方法 将未行再灌注治疗的157例AMI患者根据血白细胞计数分为四组:G1组(<8.0×109/L)35例、G2组(8.0×109/ L～12.0×109/L)43例、G3组(12.0×109/L～16.0×109/L)42例、G4组(＞16.0×109/L)37例,测定各组患者心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)水平,统计各组患者心律失常的发生率,且对其之间的相关性进行分析.结果 四组患者cTnI及CK-MB水平比较差异有统计学意义(P<0.01),G3、G4组显著高于G1、G2组(P<0.01).四组患者心律失常(窦速、房颤、室早、室速、室颤、AVB、BBB)的发生率比较差异有统计学意义(P<0.01),G3、G4组显著高于G1、G2组(P<0.01).血白细胞计数与心律失常发生率呈正相关(r=0.957,P<0.01).结论 AMI患者血白细胞计数越高,心肌梗死面积越大,心律失常特别是恶性心律失常的发生率越高.

OBJECTIVE:This study was designed to examine the impact of the antioxidant metallothionein (MT) on cardiac contractile, intracellular Ca(2+) function and oxidative stress in lipopolysaccharide (LPS)-treated mice.METHODS:Weight and age matched adult male FVB and cardiac-specific MT-overexpressing transgenic mice were injected intraperitoneally with 4 mg/kg Escherichia Coli LPS dissolved in sterile saline or an equivalent volume of pathogen-free saline (control groups). Six hours following LPS or saline injection, cardiac geometry and function were evaluated in anesthetized mice using the 2-D guided M-mode echocardiography. Mechanical and intracellular Ca(2+) properties were examined in hearts. Cell shortening and relengthening were assessed using the following indices: peak shortening (PS)-indicative of the amplitude a cell can shorten during contraction; maximal velocities of cell shortening and relengthening (± dl/dt)-indicative of peak ventricular contractility; time-to-PS (TPS)-indicative of systolic duration; time-to-90% relengthening (TR(90))-indicative of diastolic duration (90% rather 100% relengthening was used to avoid noisy signal at baseline concentration). The 360 nm excitation scan was repeated at the end of the protocol and qualitative changes in intracellular Ca(2+) concentration were inferred from the ratio of fura-2 fluorescence intensity (FFI) at two wavelengths (360/380). Fluorescence decay time was measured as an indicator of the intracellular Ca(2+) clearing rate. Glutathione/glutathione disulfide ratio and ROS generation were detected as the markers of oxidative stress.RESULTS:Heart rate was increased while EF was reduced in LPS-FVB mice and heart rate was reduced and EF increased in MT-LPS transgenic mice [(528 ± 72) beats/min vs (557 ± 69) beats/min, (66 ± 14)% vs (42 ± 10)%, P < 0.05]. Cardiomyocytes from the LPS treated FVB mice displayed significantly reduced peak shortening (PS) and maximal velocity of shortening/relengthening (±dl/dt) associated with prolonged time-to-90% relengthening (TR(90)), these effects were attenuated in cardiomyocytes from the MT-LPS mice [PS(5 ± 1.1)% vs (7.2 ± 0.8)%, dl/dt(160 ± 15) µm/s vs (212 ± 36) µm/s, -dl/dt (175 ± 32) µm/s vs (208 ± 29) µm/s, TR(90) (0.24 ± 0.03)s vs (0.19 ± 0.02)s, P < 0.05]. LPS treated mice showed significantly reduced peak intracellular Ca(2+) and electrically-stimulated rise in intracellular Ca(2+) as well as prolonged intracellular Ca(2+) decay rate without affecting the basal intracellular Ca(2+) levels, again, these effects were significantly attenuated in MT-LPS transgenic mice. Metallothionein overexpression also ablated oxidative stress [reduced ROS generation and increased glutathione/glutathione disulfide ratio, ROS (0.35 ± 0.08) A/µg protein vs (0.24 ± 0.03) A/µg protein]. GSH/GSSG 2.1 ± 0.2 vs 2.6 ± 0.4, P < 0.05.CONCLUSION:MT overexpression improved cardiac function and ablated oxidative stress in LPS treated mice.

急性冠脉综合征(ACS)是指冠脉粥样硬化斑块破裂或侵蚀,继发完全或不完全性血栓形成为病理基础的临床综合征,包括不稳定型心绞痛(UA)、非ST段抬高的心肌梗死(NSTEMI)和ST段抬高的心肌梗死(STEMI).ACS 是复杂的急性心肌缺血综合征,其病理生理学变化以冠脉斑块裂隙、糜烂和(或)破裂为基础,使斑块内高度致血栓形成物质暴露于血流中, 引起血小板在受损斑块表面黏附、活化和聚集,形成不同类型的血栓.

Inflammation, vascular proliferation. and apoptosis contribute to the process of atherosclerosis. Clopidogrel has been used to treat atherosclerosis; however, the mechanism is not entirely known. Compared with those of atorvastatin, we determined effects of clopidogrel on inflammatory factors, vascular proliferation, and apoptosis in an atherosclerosis rabbit model. New Zealand white rabbits were fed a normal diet or a high cholesterol diet for 7 weeks. The right iliac artery of animals except those in the negative control group were balloon-injured 1 week after initiation of the diet, and groups of animals were treated with clopidogrel (4 mg/kg per day), atorvastatin (2.5 mg/kg per day), or placebo (positive control group) for 6 weeks. We found that the placebo group had significant progression of atherosclerosis compared with the negative control group. In contrast, clopidogrel- or atorvastatin-treated rabbits showed a significant reduction in progression of atherosclerosis, including a low expression of high sensitivity C-reactive protein and platelet-derived growth factor, a reduced intima thickness, and reduced ratio of bcl-2/bax in the vascular wall. These results suggest that clopidogrel can retard the progression of established lesions that is related to inhibiting inflammation, cell proliferation, and promotion of cell apoptosis.

目的探讨阿托伐他汀、氯吡格雷合用对兔髂腹动脉内膜剥脱术后内膜增生的影响及其作用机制。方法将30只新西兰兔随机均分为对照组、阿托伐他汀组(他汀组)和阿托伐他汀联合氯吡格雷组(联合组)。通过髂腹动脉内膜剥脱术联合高脂喂养法建立动脉粥样硬化(AS)模型,检测各组血小板源性生长因子(PDGF)和凋亡蛋白bcl-2、bax在髂动脉内膜的表达,以及血脂、高敏C反应蛋白(hs-CRP)变化;观察动脉内膜、中膜的病理学改变,测量其厚度和面积。结果与对照组比较,他汀组和联合组PDGF mRNA表达、bcl-2/bax比值、血脂、血清hs-CRP及内膜增生均明显降低(P<0.05或<0.01)。结论阿托伐他汀、氯吡格雷合用可协同抑制兔AS模型的动脉内膜增生,其对减轻临床AS患者的内膜增生可能有益。

Objective:To explore the electrophysiological mechanisms and ablation strategy of superventricular tachycardia with R-R interval alternation.Methods:Ten patients with superventricular tachycardia and simultaneous R-R interval alternation received electrophysiological study and then ablation according to the different type of tachycardia.At first,the accessory pathway or induced tachycardia was treated.However,if atrioventricular nodal renntry tachycardia(AVNRT) was induced,the slow pathway should be ablated at the same time.Results:Of 10 patients,9 patients were with left free wall accessory pathways and AVN double pathways.The accessory pathways were first ablated,and 3 slow pathways inducing AVNRT were also modified,while the rest not inducing AVNRT remained intact.One patient had triple AVN pathways,and the slow pathways were successfully blocked.During the follow-up of 6 months to 8.4 years,there was no recurrence of tachycardia.Conclusion:Tachycardia with R-R interval alternation has a characteristic in common:coexistence of AVN double pathways.After the basic tachycardia is ablated,the slow pathway may not be intervened if it does not induce AVNRT.

Objective To investigate the concentration changes of matrix metalloproteinase-2(MMP-2),interleukin-18(IL-18) and fibrinogen in patients with acute coronary syndrome(ACS) and their significance.Methods Levels of MMP-2 and IL-18 were measured by ELISA in 32 patients with unstable angina pectoris(UAP),24 patients with acute myocardial infarction(AMI),36 patients with SAP(stable angina pectoris) and 40 healthy subjects.The level of fibrinogen was measured with the Clauss method.Results Levels of MMP-2 and IL-18 were higher in the UA and AMI groups than in the SAP group and control group(P 0.05 ﹚,while there was no significant difference in the level of fibrinogen among the four groups ﹙ P 0.05 ﹚.In patients with ACS,the peak value of MMP-2 appeared on day 1,followed by a gradual decrease up to day 10,whereas IL-18 on day 3.Conclusion MMP-2 and IL-18 play an important role in the pathogenesis of ACS.

Background: The effects of angiotensin-II type 1 receptor blockers (ARBs) on the treatment of hypertension, heart failure, and other cardiovascular diseases have been confirmed extensively. However, recent studies have emphasized the nonhemodynamic effects of these drugs. The purpose of this study was to investigate the effects of ARBs on the development of experimental autoimmune myocarditis (EAM), and to clarify the mechanisms involved.Methods: EAM model was induced in Lewis rats by injection of porcine cardiac myosin subcutaneously. We administered valsartan (a new ARB) to rats with EAM and measured blood pressure regularly. Echocardiography was performed to examine the cardiac function and heart structure of the rats. The severity of myocarditis was detected by histopathological evaluation. We evaluated antigen-specific T-cell proliferation responses to cardiac myosin by the lymphocyte proliferation assay and measured serum levels of Th1 and Th2 cytokines by enzyme-linked immunosorbent assay.Results: There was no significant difference in the blood pressure (BP) level between the groups and cardiac function of valsartan-treated rats was significantly improved compared with untreated rats. Valsartan markedly reduced the severity of myocardial lesions and suppressed lymphocyte proliferation in rats immunized with myosin. After drug administration, Th1 cytokines (IFN-gamma and IL-2) were significantly down-regulated, while Th2 cytokines (IL-4 and IL-10) were detected to undergo up-regulation.Conclusions: The results suggest that valsartan can ameliorate EAM independent of BP-lowering effects. Some of the beneficial effects of ARBs may be due to their immunomodulatory reactions in the modification of helper T-cell balance. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Toll-like receptor 4 (TLR4), a proximal signalling receptor in innate immune responses to lipopolysaccharide of gram-negative pathogens, is expressed in the heart. Accumulating evidence have consolidated the notion that TLR4 plays an essential role in the pathogenesis of cardiac dysfunction. However, the molecular mechanisms of TLR4 responsible for ischemia-induced cardiac dysfunction remain unclear. To address the signalling mechanisms of TLR4-deficiency cardioprotection against ischemic injury, in vivo regional ischemia was induced by occlusion of the left anterior descending coronary artery in wild-type (WT) C3H/HeN and TLR4-mutated C3H/HeJ mice. The results demonstrated that blunted ischemic activation of p38 mitogen-activated protein kinase and JNK signalling occurred in C3H/HeJ hearts versus C3H/HeN hearts, while ERK and AMP-activated protein kinase (AMPK) signalling pathways were augmented during ischemia in C3H/HeJ hearts versus C3H/HeN hearts. Intriguingly, ischemia-stimulated endoplasmic reticulum stress was higher in C3H/HeN hearts than that in C3H/HeJ as demonstrated by up-regulation of Grp78/BiP, Gadd153/CHOP and IRE-1 alpha. Myocardial infarct, caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining demonstrated that C3H/HeN hearts suffered more damage than those of C3H/HeJ hearts during ischemia. Moreover, isolated cardiomyocytes from C3H/HeJ hearts showed resistance to hypoxia-induced contractile dysfunction compared to those from C3H/HeN hearts, which are associated with greater hypoxic activation of AMPK and ERK signalling, better intracellular Ca2+ handling in C3H/HeJ versus C3H/HeN cardiomyocytes. These findings suggest that the cardioprotective effects against ischemic injury of hearts with deficiency in TLR4 signalling may be mediated through modulating AMPK and ERK signalling pathway during ischemia.

Objective To evaluate the efficacy and safety of olmesartan medoxomil compared with valsartan in patients with mild to moderate essential hypertension. Methods A total 240 eligible subjects were randomized at 1∶1 ratio to receive olmesartan medoxomil 20-40 mg or valsartan 80-160 mg,once daily for 8 weeks. Results The mean trough reduction in SeDBP from baseline was no difference between olmesartan medoxomil and valsartan groups after 4 weeks \[(10.58±6.82) mmHg vs (9.38±7.16) mmHg,P0.05\] and 8 weeks treatment \[(15.72±6.03) mmHg vs (14.12±6.79) mmHg,P0.05\]. After 4 weeks treatment,the patients with double dose in olmesartan and valsartan group were 60% and 61.74%,the double dose efficiency were 52.22% and 51.85% respectively(P0.05). The incidence of study drug-related adverse event (AE) in olmesartan group (3.33%) was similar to that in valsartan group (7.5%,P0.05). No SAE was occurred. Conclusion Olmesartan medoxomil at oral dase of 20~40 mg once daily was effective and safe for hypertension treatment and effect was similar to valsartan 80~160 mg once daily.

目的 探讨充血性心力衰竭(CHF)患者应用血管紧张素转换酶抑制剂 (ACEI)/血管紧张素受体抑制剂(ARB)和(或)β受体阻滞剂等药物治疗后,血清Ⅰ型前胶原羧基端肽(PⅠCP)和Ⅲ型前胶原氨基端肽(PⅢNP)的变化及其临床意义.方法 86例CHF患者根据治疗药物的不同分三组:ACEI/ARB组,29例,倍他乐克组,24例;ACEI/ARB+倍它乐克组,33例;47例体检健康者为对照组.采用放射免疫法测定对照组、CHF患者入院时及规范治疗6 w后血清PⅠCP和PⅢNP浓度.应用多普勒超声测算:左室射血分数(LVEF)、E峰和A峰及两者比值(VE/VA)、左室内径(LVID).结果 各组CHF患者及对照组之间基本临床资料(性别、年龄等)差异不显著.各组CHF患者NYHA分级和LVEF也无显著差异.CHF患者血清PⅠCP和 PⅢNP均明显高于对照组(P＜0.01).3组CHF患者治疗6 w后,NYHA分级和LVEF较治疗前均明显改善(P＜0.01,P＜0.05),血清PⅠCP 和PⅢNP较治疗前也均明显降低(P＜0.01).相关分析显示,PⅠCP和 PⅢNP水平与LVID呈正相关,与LVEF、VE/VA呈负相关.结论 血清PⅠCP 和PⅢNP水平可预测CHF患者药物治疗反应效果.

Lipopolysaccharide (LIPS), a component of the outer membrane of Gram-negative bacteria, plays a key role in cardiac dysfunction in sepsis. Low circulating levels of insulin-like growth factor 1 (IGF-1) are found in sepsis, although the influence of IGF-1 on septic cardiac defect is unknown. This study was designed to examine the impact of IGF-1 on LPS-induced cardiac contractile and intracellular Ca2+ dysfunction, activation of stress signal and endoplasmic reticulum (ER) stress. Mechanical and intracellular Ca2+ properties were examined in cardiomyocytes from Fast Violet B and cardiac-specific IGF-1 overexpression mice treated with or without LPS (4 mg kg(-1), 6 h). Reactive oxygen species (ROS), protein carbonyl formation and apoptosis were measured. Activation of mitogen-activated protein kinase pathways (p38, c-jun N-terminal kinase [JNK] and extracellular signal-related kinase [ERK]), ER stress and apoptotic markers were evaluated using Western blot analysis. Our results revealed decreased peak shortening and maximal velocity of shortening/relengthening and prolonged duration of relengthening in LPS-treated Fast Violet B cardiomyocytes associated with reduced intracellular Ca2+ decay. Accumulation of ROS protein carbonyl and apoptosis were elevated after LPS treatment. Western blot analysis revealed activated p38 and JNK, up-regulated Bax, and the ER stress markers GRP78 and Gadd153 in LPS-treated mouse hearts without any change in ERK and Bcl-2. Total protein expression of p38, JNK, and ERK was unaffected by either LPS or IGF-1. Interestingly, these LPS-induced changes in mechanical and intracellular Ca2+ properties, ROS, protein carbonyl, apoptosis, stress signal activation, and ER stress markers were effectively ablated by IGF-1. In vitro LPS exposure (1 mu g mL(-1)) produced cardiomyocyte mechanical dysfunction reminiscent of the in vivo setting, which was alleviated by exogenous IGF-1 (50 nM). These data collectively suggested a beneficial of IGF-1 in the management of cardiac dysfunction under sepsis.

Objective:To study the relationship between the levels of serum homocysteine(Hcy) and results of coronary angiography in coronary patients with or without essential hypertension(EH).Methods:Seventy-two patients and 24 control were examined the levels of serum homocysteine and hospitalized to receive percutaneous transluminal coronary angioplasty and stent.Thirty-nine patients only with coronary heart diseases(group a),33 coronary patients with essential hypertension(group b) and 24 control(group c) were studied,according to the results of coronary angiography.Then,to analyze the relationship between the levels of serum homocysteine and results of coronary angiography in these three groups.Results:There is a statistical significance between the levels of serum homocysteine and the crucial amount of branches of coronary.The higher the levels of serum homocysteine,the more crucial amount of branches of coronary(P0.01).Moreover,the levels of serum homocysteine were highest in group b compared with group a and group c.Conclusion:There is a good relationship between the levels of serum homocysteine and results of coronary angiography.To prevents and diagnosis of coronary heart disease and hypertension,it has a high clinical value to measure the levels of serum homocysteine.

Radix Astragali, a Chinese medicinal herb, consists of polysaccharides and flavonoids as its main active ingredients. It has been widely used for treatment of cardiovascular diseases such as heart failure, angina pectoris, myocardial infarction and stroke in Asian countries. This study was designed to evaluate the effect of Radix Astragali on myocardial dysfunction, cardiac remodeling and morphological alteration in an experimental model of autoimmune myocarditis, a clinical condition often resulting in dilated cardiomyopathy. Experimental autoimmune myocarditis was established with a subcutaneous injection of porcine cardiac myosin into rear footpad in Lewis rats. Radix Astragali treatment was delivered via an intravenous injection (0.2 ml/100 g body weight, daily) for 3 weeks. Results from transthoracic echocardiography indicated that experimental autoimmune myocarditis led to impaired myocardial contractile function which was reconciled by Radix Astragali. The experimental autoimmune myocarditis triggered profound inflammation and fibrosis in myocardium as assessed by hematoxylin and eosin (H and E) and Masson’s trichrome staining. Interestingly, Radix Astragali significantly attenuated autoimmune myocarditis-induced myocardial inflammation and fibrosis. Similarly, Radix Astragali treatment alleviated autoimmune myocarditis-triggered overt lymphocyte proliferation. Furthermore, Radix Astragali significantly attenuated elevated levels of the Th1 cytokines (IFN-γ and IL-2), and increased the Th2 cytokines (IL-4 and IL-10) in autoimmune myocarditis. Collectively, our data revealed that Radix Astragali effectively protected against cardiac functional and morphological aberrations in experimental autoimmune myocarditis.

Myocardial ischemia/reperfusion injury involves a robust inflammatory response especially activation of toll-like receptor 4 (TLR4), a proximal signaling receptor in innate immune responses to lipopolysaccharide of Gram-negative pathogens. TLR4 is expressed in the heart and vasculature, the deficiency of which was shown to protect the heart against ischemia/reperfusion injury. However, the molecular mechanisms behind TLR4 deficiency-induced cardioprotection against ischemic damage remain unclear. The AMP-activated protein kinase (AMPK), an intracellular energy gauge, plays an important role in limiting cardiac damage following by ischemia, thus we hypothesized that AMPK maybe a mediator of TLR4-deficiency cardioprotection against ischemic injury. To test this hypothesis, In vivo regional ischemia was induced by occlusion of the left anterior descending (LAD) coronary artery in wild type (WT) C3H/HeN and TLR4-deficient C3H/HeJ mice, which carry a natural mutation of TLR4. Immunoblotting analysis was performed to assess the activation of AMPK and TLR4 downstream signal, the mitogen-activated protein kinase (MAPK). The endoplasmic reticulum (ER) chaperons, Grp78/BiP and Gadd153/CHOP, and ER integral membrane protein IRE1α were also monitored. The results demonstrated that C3H/HeJ hearts had impaired ischemic MAPK and AMPK activation compared to WT C3H/HeN hearts, i.e. activation of p38 MAPK and JNK was blunted, while ERK and AMPK signaling pathways were augmented during ischemia in C3H/HeJ hearts. Intriguingly, ischemia-stimulated ER stress was higher in WT C3H/HeN hearts than that in C3H/HeJ as demonstrated by up-regulation of Grp78/BiP, Gadd153/CHOP and IRE1α. Caspase-3 activity and TUNEL staining results showed that WT C3H/HeN hearts have more damages than those of C3H/HeJ hearts. Moreover, isolated cardiomyocytes from C3H/HeJ hearts showed resistance to ischemia-induced contractile dysfunction compared to WT C3H/HeN hearts. These findings suggest that the cardioprotective effects against ischemic injury of TLR4-deficient hearts may mediated through augmentation of AMPK and ERK while alleviation of p38 MAPK and JNK inflammatory signaling pathways. This research has received full or partial funding support from the American Heart Association, AHA National Center.

睡眠呼吸障碍(SDB)是指由于上气道阻力增加或呼吸中枢驱动障碍,导致的低通气或呼吸暂停(SA),并由此引起一系列病理生理改变和症状的临床征候群.主要包括:鼾症、阻塞性呼吸暂停低通气综合征(OSAHS)、中枢性呼吸暂停综合征(CSAS)、肥胖低通气综合征(OHS)、上气道阻力综合征(UARS)等.本文主要就OSAHS、CSAS与心血管疾病的关系进行讨论.

<正>患者男性,31岁,因反复心悸5年余入院。既往心悸时记录的心电图(图略)示窄QRS波群心动过速。临床诊断为阵发性室上性心动过速,拟行射频导管消融(下称消融)。