A dynamic Brugada sign due to left anterior descending coronary artery occlusion

Brugada phenocopies (BrP) include several conditions with a common electrocardiographic (ECG) pattern that are indistinguishable from classical Brugada syndrome (BrS). In this report, we describe two cases of acute myocardial infarction (AMI) presenting as BrP. The majority of cases of BrP in AMI have been reported due to right coronary artery (RCA) occlusion. Rarely, the left anterior descending artery (LAD) is incriminated as the cause. In both our cases of BrP, LAD was the culprit vessel.     

KATP通道对缺血性心肌电平衡的维护作用及机制

目的：利用异丙肾上腺素（ISO）诱导大鼠心肌缺血性损伤模型和心肌细胞损伤模型,并对其进行药物干预,探讨心肌ATP敏感性钾 通道（KATP通道）维持缺血性心肌电平衡的作用与机制。方法：在动物实验中,将雄性SD大鼠,随机分为5组,正常对照组大鼠皮下注射0.9% 氯化钠溶液,其余各组大鼠均皮下注射等量1 g ? L -1 ISO（qd）,连续9 d,其间,在第7~9 d,除了正常对照组和模型组外,其他3组大鼠还 分别灌胃给予1.75 g ? L -1 普萘洛尔（PRO）2 mL ? kg -1 ? d -1 、5 g ? L -1 曲美他嗪（VAS）2 mL ? kg -1 ? d -1 或腹腔注射给予5 g ? L -1 二苯基碘（DPI） 1 mL ? kg -1 ? d -1 。在造模期间不同时间点,对各组大鼠进行心电图检查,并制备心肌标本,检测其中KATP通道亚基KIR6.2蛋白表达水平。 在细胞实验中,将H9C2心肌细胞分成对照组（不给药）、ISO组、ISO+ PRO组、ISO+DPI组和ISO+VAS组,后3组细胞均在1 μmol ? L -1 ISO加入前30 min,分别给予2 μmol ? L -1 PRO、10 μmol ? L -1 DPI和10 μmol ? L -1 VAS,且在加入ISO后,与ISO组细胞一样,再孵育1 和24 h,采用实时荧光定量 PCR法测定各组细胞中KATP通道亚基KIR6.2和SUR2A基因表达水平。结果：大鼠实验显示,与正常对照组相比, 模型组大鼠在造模的第3、7 d,心电图参数QTc明显缩短,心率加快（P ＜0.05）,且心肌中KIR6.2蛋白表达明显增多（P ＜0.01）,而造 模9 d后,其QTc明显延长（P ＜0.01）,心率减慢（P ＜0.05）,心肌中KIR6.2蛋白表达显著降低（P ＜0.01）;ISO+ PRO、ISO+DPI 和ISO+VAS各组大鼠在持续3 d分别接受3种药物治疗后,其QTc较模型组明显缩短,心率升高,均趋于恢复正常水平。细胞实验显示, 与对照组相比,ISO组H9C2细胞经ISO孵育1 h后,KIR6.2和SUR2A的mRNA表达显著上调（P ＜0.05）,而在ISO孵育24 h后, KIR6.2和SUR2A的mRNA表达显著下调（ P ＜0.01）;与ISO组相比,各给药组细胞经ISO孵育1 h后,KIR6.2和SUR2A的mRNA表 达均有不同程度下调,而在ISO孵育24 h后,KIR6.2和SUR2A的mRNA表达均显著上调（P ＜0.05或P ＜0.01）。结论：KATP通道对 维护缺血性心肌电平衡起重要作用。持续性激动β受体、氧化应激或能量供应不足等体内多条途径都会影响KATP通道的表达和功能,而保护 KATP通道功能,对于维持心电平衡,抑制心律失常基质形成,意义重大。     

Exosomes in Mesenchymal Stem Cells,a New Therapeutic Strategy for Cardiovascular Diseases?

Cardiovascular diseases (CVDs) are still a major cause of people deaths worldwide, and mesenchymal stem cells (MSCs) transplantation holds great promise due to its capacity to differentiate into cardiovascular cells and secrete protective cytokines, which presents an important mechanism of MSCs therapy for CVDs. Although the capability of MSCs to differentiate into cardiomyocytes (CMCs), endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) has been well recognized in massive previous experiments both in vitro and in vivo, low survival rate of transplanted MSCs in recipient hearts suggests that therapeutic effects of MSCs transplantation might be also correlated with other underlying mechanisms. Notably, recent studies uncovered that MSCs were able to secret cholesterol-rich, phospholipid exosomes which were enriched with microRNAs (miRNAs). The released exosomes from MSCs acted on hearts and vessels, and then exerted anti-apoptosis, cardiac regeneration, anti-cardiac remodeling, anti-inflammatory effects, neovascularization and anti-vascular remodeling, which are considered as novel molecular mechanisms of therapeutic potential of MSCs transplantation. Here we summarized recent advances about the role of exosomes in MSCs therapy for CVDs, and discussed exosomes as a novel approach in the treatment of CVDs in the future.     

Decrease in Plasma Cyclophilin A Concentration at 1 Month after Myocardial Infarction Predicts Better Left Ventricular Performance and Synchronicity at 6 Months: A Pilot Study in Patients with ST Elevation Myocardial Infarction

Background: Cyclophilin A (CyPA) concentration increases in acute coronary syndrome. In an animal model of acute myocardial infarction, administration of angiotensin-converting-enzyme inhibitor was associated with lower left ventricular (LV) CyPA concentration and improved LV performance. This study investigated the relationships between changes in plasma CyPA concentrations and LV remodeling in patients with ST-elevation myocardial infarction (STEMI).Methods and Results: We enrolled 55 patients who underwent percutaneous coronary intervention for acute STEMI. Plasma CyPA, matrix metalloproteinase (MMP), interleukin-6 and high-sensitivity C-reactive protein concentrations were measured at baseline and at one-month follow-up. Echocardiography was performed at baseline and at one-, three-, and six-month follow-up. Patients with a decrease in baseline CyPA concentration at one-month follow-up (n = 28) had a significant increase in LV ejection fraction (LVEF) (from 60.2 ± 11.5% to 64.6 ± 9.9%, p < 0. 001) and preserved LV synchrony at six months. Patients without a decrease in CyPA concentration at one month (n = 27) did not show improvement in LVEF and had a significantly increased systolic dyssynchrony index (SDI) (from 1.170 ± 0.510% to 1.637 ± 1.299%, p = 0.042) at six months. Multiple linear regression analysis showed a significant association between one-month CyPA concentration and six-month LVEF. The one-month MMP-2 concentration was positively correlated with one-month CyPA concentration and LV SDI.Conclusions: Decreased CyPA concentration at one-month follow-up after STEMI was associated with better LVEF and SDI at six months. Changes in CyPA, therefore, may be a prognosticator of patient outcome.     

Repair mechanisms of bone marrow mesenchymal stem cells in myocardial infarction

The prognosis of patients with myocardial infarction (MI) and resultant chronic heart failure remains extremely poor despite advances in optimal medical therapy and interventional procedures. Animal experiments and clinical trials using adult stem cell therapy following MI have shown a global improvement of myocardial function. Bone marrow-derived mesenchymal stem cells (MSCs) hold promise for cardiac repair following MI, due to their multilineage, self-renewal and proliferation potential. In addition, MSCs can be easily isolated, expanded in culture, and have immunoprivileged properties to the host tissue. Experimental studies and clinical trials have revealed that MSCs not only differentiate into cardiomyocytes and vascular cells, but also secrete amounts of growth factors and cytokines which may mediate endogenous regeneration via activation of resident cardiac stem cells and other stem cells, as well as induce neovascularization, anti-inflammation, anti-apoptosis, anti-remodelling and cardiac contractility in a paracrine manner. It has also been postulated that the anti-arrhythmic and cardiac nerve sprouting potential of MSCs may contribute to their beneficial effects in cardiac repair. Most molecular and cellular mechanisms involved in the MSC-based therapy after MI are still unclear at present. This article reviews the potential repair mechanisms of MSCs in the setting of MI.     

血清CREG蛋白在急性心肌梗死早期的表达研究

目的：探讨血清中CREG蛋白在急性心肌梗死发作早期的表达情况,尝试为临床心肌缺血的极早期诊断提供一种新的血清标志分子。方法：在2010年6月至2010年11月期间,入选在沈阳军区总医院心内科住院治疗的急性ST段抬高型心肌梗死患者50例及非AMI对照50例,于AMI组胸痛发作后的不同时间点采血测定CK、CK—MB、LDH和cTnT,同时应用Westem blot技术测定血清中CREG蛋白的含量,并与对照组比较。结果：AMI组发病72小时内的血清中CREG蛋白表达均较对照组有不同程度的增高（P〈0．05）。胸痛开始2h内,AMI组血清中CREG的含量即明显增高,其在2h、4h及6h的含量显著高于对照组（P〈0．001）。在胸痛已经发作2小时内,两组间血清cTnT、CK、CK-MB及LDH水平比较无统计学意义（P〉0．05）。结论：CREG在AMI患者血清中的表达增高．其在血清中表达时间早于cTNT及CK-MB。     

Acute and chronic administration of disodium disuccinate astaxanthin (CardaxTM) produces marked cardioprotection in dog hearts

Previous results from our laboratory have shown that a novel carotenoid derivative (disodium disuccinate astaxanthin; Cardax^TM) produced dose-related reductions in myocardial infarct size (IS) in Sprague–Dawley rats when it was administered at any of three doses (25, 50 and 75 mg/kg, iv) on four consecutive days, followed by the acute infarct size study on day 5. Maximum salvage occurred at the highest dose (75 mg/kg) tested, and was shown as a 56% reduction in IS. In the present follow-up study, we used a more relevant large animal model, the dog, and looked at the effect of administering Cardax^TM iv either acutely 2 h prior to occlusion (N = 8) or for 4 days at 50 mg/kg iv as previously done in the rat model (N = 6). The results were compared to a saline vehicle-treated group (N = 10). In all groups, dogs were subjected to 60 min of left anterior descending (LAD) coronary artery occlusion and 3 h of reperfusion. IS was determined using a triphenyltetrazolium chloride (TTZ) histochemical stain and was expressed as a percent of the area at risk (IS/AAR). IS/AAR was 20.9 ± 1.6 % (mean ± S.E.M.) in controls and was reduced to 11.0± 1.7% (47.3% salvage; p < 0.01) in dogs treated only once iv at 2 h prior to occlusion, and 6.6± 2.8% (68.4% salvage; p < 0.001) in dogs treated for 4 days. In the chronic treatment group, two of the three dogs with plasma concentrations of non-esterified astaxanthin above 1 M had 0% IS/AAR (100% cardioprotection). These results suggest that Cardax^TM has marked cardioprotective properties in both rodents and canines. Thus, Cardax^TM may be a novel and powerful new means to prevent myocardial injury and/or necrosis associated with elective and/or urgent cardiac surgical interventions such as coronary angioplasty and stenting, as well as coronary artery bypass surgery (CABG).     

Virtual reality of stem cell transplantation to repair injured myocardium

The search for the fountain of youth continues into the 21st century with hopes that embryonic or hematopoietic stem cells (SC) will repair injured tissues in the heart, lungs, pancreas, muscles, nerves, liver, or skin. This commentary focuses on the potential of SC for inducing cardiac regeneration after myocardial injury, the barriers to SC treatment that need to be overcome for ensuring successful cardiac repair, and the experimental approaches that can be applied to the problem.     

Role of Reactive Oxygen Species in the Sensitivity of Rat Hypertrophied Myocardium to Ischemia

The relationship between hydroxyl radical (OH*) generation in the zone of ischemia/reperfusion and the size of infarction formed was investigated in 18-22-week-old anaesthetized male SHRSP and Wistar rats using a myocardial microdialysis technique. The marker of OH* generation, 2,3-dihydroxybenzoic acid (2,3-DHBA), was analyzed in dialyzates by high performance liquid chromatography with electrochemical detection. Myocardial ischemia was induced by ligation of the descending branch of the left main coronary artery for 30 min. The mean value of basal 2,3-DHBA level in the dialyzate samples from SHRSP (243 +/- 21 pg for 30 min) was significantly higher than that from Wistar rats (91 +/- 4 pg for 30 min, p < 0.0002); it positively correlated with left ventricular hypertrophy (r = 0.806; p < 0.05). During reperfusion total 2,3-DHBA output was 1.8-fold higher in SHRSP than in Wistar rats (659 +/- 60 pg versus 364 +/- 66 pg for 60 min, respectively, p < 0.0002). At the same time, 2,3-DHBA increase above the basal level was the same in Wistar and SHRSP rats (181 +/- 25 and 172 +/- 36 pg for 60 min, respectively). The infarct size in SHRSP (45.4 +/- 4.3%) was significantly higher (p < 0.05) than in Wistar rats (32.8 +/- 3.3%). There was a significant positive correlation between basal level of 2,3-DHBA and total reperfusion 2,3-DHBA content in SHRSP (r = 0.752; p < 0.05). Thus, data obtained clearly indicate that the hypertrophied myocardium of SHRSP was less tolerant to ischemia/reperfusion than that of Wistar rats due to chronically increased OH* production and enhanced total OH* output during reperfusion. Greater myocardial damage in SHRSP than in Wistar rats following the equal increase in OH* production above the basal level suggests the existence of deficit of the antioxidant defense in the hypertrophied myocardium.