利心丸联合伊伐布雷定治疗老年稳定性心力衰竭的临床研究

目的探讨利心丸联合盐酸伊伐布雷定片治疗老年稳定性心力衰竭的临床疗效。方法选取2016年5月—2018年5月在黑龙江省森工总医院治疗的老年稳定性心力衰竭患者152例,根据用药的差别分为对照组(76例)和治疗组(76例)。对照组口服盐酸伊伐布雷定片,5 mg/次,2次/d,经两周治疗后,若静息心率持续大于60次/min,可增至7.5 mg/次,2次/d;若静息心率持续低于50次/min,可下调至2.5mg/次,2次/d;若心率为50～60次/min,则维持5mg/次,2次/d。治疗组在对照组基础上口服利心丸,9g/次,3次/d。两组患者均经2周治疗。观察两组患者临床疗效,同时比较治疗前后两组患者左心室射血分数(LVEF)、左心室收缩末期内径(LVESD)、左心室收缩末期容积(LVESV)、左室舒张末期内经(LVEDD)、6分钟步行距离(6WMT)、西雅图心绞痛量表(SAQ)积分、GQOLI-74及血清N末端B型钠尿肽原(NT-proBNP)、胱抑素C(Cys-C)、心肌肌钙蛋白T(cTnT)、可溶性晚期糖基化终末产物受体(sRAGE)、内皮素-1(ET-1)、可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(s VCAM-1)水平和miR-423-5p。结果治疗后,对照组和治疗组临床有效率分别为81.58%和97.37%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者LVEE均明显升高(P0.05),LVESV、LVEDD和LVESD均明显下降(P0.05),且治疗组患者心功能指标水平明显好于对照组(P0.05)。治疗后,两组患者6WMT、SAQ积分和GQOLI-74评分均显著升高(P0.05),且治疗组患者这些评分明显高于对照组(P0.05)。治疗后,两组患者血清NT-proBNP、Cys-C、cTnT、miR-423-5p、sRAGE、ET-1、sVCAM-1、sICAM-1水平均明显下降(P0.05),而NO水平明显升高(P0.05),且治疗组患者这些血清学指标明显好于对照组(P0.05)。结论利心丸联合盐酸伊伐布雷定片治疗老年稳定性心力衰竭可有效改善患者心功能,促进血管内皮功能改善,提高患者运动耐量。     

甲状腺素对胸部火器伤后心功能不全治疗作用的实验研究

目的　观察胸部火器伤后甲状腺激素 (FT3)变化及其对伤后心功能不全的治疗作用。方法 :　家兔 18只 ,随机分为 3组。A组 :正常对照组 6只 ;B组 :火器伤组 6只 ;C组 :FT3治疗组 6只。监测平均动脉压、左室舒张末压、中心静脉压、FT3及心肌肌钙蛋白T(cTnT) ,观察心肌病理及超微结构。结果　B组伤后6小时平均动脉压 (6 1.1± 15 .4)mmHg,明显低于A组 (10 1.3± 17.5 )mmHg ,左室舒张末压 (39.6± 7.7)mmHg及中心静脉压 (2 0 .93± 1.97)cmH2 O ,显著高于A组 [(16 .3± 11.0 )mmHg ,(6 .5 4± 0 .5 2 )cmH2 O],cTnT漏出较A组增加明显 ,血FT3(1.32± 0 .37)ng/ml浓度明显低于A组 (5 .16± 1.45 )ng/ml,心肌间质大量红细胞浸润。治疗组平均动脉压明显高于B组 ,中心静脉压及左室舒张末压明显低于B组 ,FT3浓度接近正常水平 ,明显高于B组。心肌肿胀减轻 ,间质出血、肌丝断裂和溶解减轻现象明显。结论　胸壁心前区切线位火器伤后造成心肌病理损害及心功能不全 ;甲状腺激素明显减低 ,与心功能减退有一致性关系 ;纠正伤后低T3状态 ,有显著的治疗效果。     

A combination of increased Rho kinase activity and N-terminal pro-B-type natriuretic peptide predicts worse cardiovascular outcome in patients with acute coronary syndrome

Background

Recent experimental evidence suggests that the Rho/Rho-kinase (ROCK) system may play an important role in the pathogenesis of acute coronary syndrome (ACS) but there are little clinical data. This study examined if ROCK activity is increased in patients with acute coronary syndrome and if ROCK activity predicts long‐term cardiovascular event.

Method

Blood samples were collected from 188 patients within 12 h after admission for ACS (53% men; aged 70 ± 13) and from 61 control subject. The main outcome measures were all cause mortality, readmission with ACS or congestive heart failure (CHF) from presentation within around 2 years (mean:14.4 ± 7.2 months; range: 0.5 to 26 months).

Results

ROCK activity increased in ST elevation myocardial infarction (STEMI, n = 90) (3.33 ± 0.93), non-STEMI (NSTEMI, n = 68) (3.37 ± 1.04) and unstable angina (UA, n = 30) (2.53 ± 0.59) groups when compared with disease controls (n = 31) (2.06 ± 0.38, all p < 0.001) and healthy controls (n = 30) (1.54 ± 0.43, all p < 0.001). There were 24 deaths, 34 readmissions with ACS and 15 admissions with CHF within 2 years. Patients with a high N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high ROCK activity on admission had a five-fold risk of a cardiovascular event (RR: 5.156; 95% CI: 2.180–12.191) when compared to those with low NT-proBNP and low ROCK activity.

Conclusion

ROCK activity was increased in patients with ACS, particularly in those with myocardial infarction. The combined usage of both ROCK activity and NT-proBNP might identify a subset of ACS patients at particularly high risk.     

心肌肌钙蛋白T在急性心肌梗死诊断中的意义

目的探讨心肌肌钙蛋白T(cTnT)在急性心肌梗死(AMI)诊断中的意义。方法同时测定患者血清中的cTnT,肌酸激酶同工酶(CK-MB),统计出住院被确诊为AMI患者在早期这两项指标的阳性率,然后比较其敏感性、特异性。结果在AMI患者就诊时cTnT的阳性率是89%而CK-MB的阳性率是45%,cTnT和CK-MB两组数据差异有统计学意义(P0.01)。观察AMI患者cTnT阳性持续时间可达14d左右。结论在诊断AMI时,cTnT具有检测方便、快速,出现时间早,敏感性、特异性高,对AMI患者的早期诊断具有很好的价值。     

microRNA21对急性心肌梗死早期诊断及短期预后判断的价值

【摘要】 目的 探讨血浆微小RNA 21（miR 21）对急性心肌梗死(AMI)早期诊断及短期预后判断的价值。方法 纳入AMI患者62例(AMI组),另选取同期在本院体检中心健康体检者30例（对照组）。AMI组于急性胸痛发作6h以内、12h、24h、7d、14d采集静脉血,通过定量逆转录聚合酶链反应（qRT PCR）检测血浆miR 21相对表达水平;采用电化学免疫荧光法检测心肌肌钙蛋白T（cTnT）水平。并随访6个月观察主要心血管不良事件（MACE）的发生情况。结果 ①AMI组患者入院6h以内cTnT水平及血浆miR 21相对表达水平明显高于对照组（P＜001）。②血浆miR 21水平在入院6h内开始增高,12h达到高峰,24h、7d、14d逐渐下降至接近正常。cTnT在入院6h内开始增高,24h达到高峰,7d、14d逐渐下降至接近正常。③入院6h以内和入院12h血浆miR 21的ROC曲线下面积（AUC）分别为0939（95%CI：0893～0984,P=0000）和0956（95%CI：0918～0994,P=0000）;入院6h以内和入院12h血浆cTnT的AUC分别为0964（95%CI：0932～0996,P=0000）和0979（95%CI：0956～1000,P=0000）。④随访6个月后,发生MACE的患者在入院6h、12h、24h、7d、14d血浆miR 21相对表达水平与未发生MACE的患者比较,差异均有统计学意义（均P＜001）。结论 检测miR 21水平对AMI的早期诊断和预后评估具有一定的临床参考价值,但并不优于cTnT的检测价值。     

Calcium binding kinetics of troponin C strongly modulate cooperative activation and tension kinetics in cardiac muscle

Tension development and relaxation in cardiac muscle are regulated at the thin filament via Ca²⁺ binding to cardiac troponin C (cTnC) and strong cross-bridge binding. However, the influence of cTnC Ca²⁺-binding properties on these processes in the organized structure of cardiac sarcomeres is not well-understood and likely differs from skeletal muscle. To study this we generated single amino acid variants of cTnC with altered Ca²⁺ dissociation rates (k_off), as measured in whole troponin (cTn) complex by stopped-flow spectroscopy (I61Q cTn > WT cTn > L48Q cTn), and exchanged them into cardiac myofibrils and demembranated trabeculae. In myofibrils at saturating Ca²⁺, L48Q cTnC did not affect maximum tension (T_max), thin filament activation (k_ACT) and tension development (k_TR) rates, or the rates of relaxation, but increased duration of slow phase relaxation. In contrast, I61Q cTnC reduced T_max, k_ACT and k_TR by 40-65% with little change in relaxation. Interestingly, k_ACT was less than k_TR with I61Q cTnC, and this difference increased with addition of inorganic phosphate, suggesting that reduced cTnC Ca²⁺-affinity can limit thin filament activation kinetics. Trabeculae exchanged with I61Q cTn had reduced T_max, Ca²⁺ sensitivity of tension (pCa₅₀), and slope (n_H) of tension-pCa, while L48Q cTn increased pCa₅₀ and reduced n_H. Increased cross-bridge cycling with 2-deoxy-ATP increased pCa₅₀ with WT or L48Q cTn, but not I61Q cTn. We discuss the implications of these results for understanding the role of cTn Ca²⁺-binding properties on the magnitude and rate of tension development and relaxation in cardiac muscle.     

Cardioprotective and antiarrhythmic effect of U50,488H in ischemia/reperfusion rat heart

The objective of this study was to investigate the protective effect of U50,488H, a selective κ-opioid receptor agonist, in the ischemia/reperfusion (I/R) rat and to delineate the underlying mechanism. Rat heart I/R injury was induced by occluding the left anterior descending coronary artery for 45 min and restoring perfusion for 120 min. U50,488H or vehicle was intravenously injected before ischemia. Electrocardiogram, heart rate (HR), arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (+dp/dt _max), and diastolic function (−dp/dt _max) were monitored in the course of the experiment. Myocardial infarction size was evaluated. Plasma concentrations of cardiac troponin T (cTnT), creatine kinase (CK), and lactate dehydrogenase (LDH) were measured. Single rat ventricular myocyte was obtained by enzymatic dissociation method. The potassium currents (I _K) of isolated ventricular myocytes were recorded with the whole-cell configuration of the patch-clamp technique. Compared with the sham control group, no significant change was found in HR, while ABP, LVP and ±dp/dt _max were significantly reduced in the I/R group. Administration of U50,488H significantly lowered HR in both control and I/R groups. Compared with the vehicle-treated I/R group, administration of U50,488H had no significant effect on I/R-induced reduction in ABP, LVP, and ±dp/dt _max. However, this treatment significantly reduced the myocardial infarction size, and markedly decreased the contents of plasma cTnT, CK and LDH. During ischemia and reperfusion, the incidence of ventricular arrhythmia in U50,488H-treated rats was significantly reduced. These effects were independent of the bradycardia induced by U50,488H, as the reducing infarct size and antiarrhythmic effect of U50,488H were still observed in animals in which heart rate was kept constant by electrical pacing. U50,488H and BRL-52537 still produced an antiarrhythmic effect when the rat heart was subjected to a shorter ischemic period of 10 min occlusion of coronary artery, which produced no infarction. I _K of the myocytes were inhibited by U50,488H in a dose-dependent manner in normal and hypoxic rat ventricular myocytes. However, the effects of U50,488H on I _K did not show any significant difference in normal and hypoxic myocytes. The above-described effects of U50,488H were totally blocked by nor-Binaltorphimine, a selective κ-opioid receptor antagonist. The results suggest that κ-opioid agonist U50,488H exerts its direct cardioprotective and antiarrhythmic effects against I/R via κ-opioid receptor, which participates in the regulation of potassium channels in normal and hypoxic ventricular myocytes. The first two authors contributed equally to this project.     

Elevated Cardiac Troponin T in Patients With Skeletal Myopathies

Background

Cardiac troponins are often elevated in patients with skeletal muscle disease who have no evidence of cardiac disease.