Statins, fenofibrate, and quinapril increase clot permeability and enhance fibrinolysis in patients with coronary artery disease

BACKGROUND: Aspirin increases fibrin clot porosity and susceptibility to lysis. It is unknown whether other drugs, in combination with aspirin, used in the treatment of coronary artery disease (CAD) might affect clot structure and resistance to lysis. AIM: The aim of the study was to assess the effects of statins, fibrates, or angiotensin-converting enzyme inhibitors (ACEIs) on fibrin clot properties. PATIENTS AND METHODS: In a randomized double-blind study, men with advanced CAD taking low-dose aspirin were assigned to receive one of the four drugs: simvastatin 40 mg day(-1) (n = 13), atorvastatin 40 mg day(-1) (n = 12), fenofibrate 160 mg day(-1) (n = 12), and quinapril 10 mg day(-1) (n = 11) for 28 +/- 2 days. Moreover, CAD patients (n = 13) taking aspirin (75 mg day(-1)) for 8 weeks were studied after additional 4 weeks on an open-label basis. Thirty men served as healthy controls. Plasma clot permeability and tissue plasminogen activator-induced fibrinolysis were evaluated at baseline and after drug administration. RESULTS: Permeability increased following the administration of simvastatin (by 20%; P = 0.01), atorvastatin (by 22%; P = 0.001), fenofibrate (by 16%; P = 0.02), and quinapril (by 13%; P = 0.04) like for aspirin (P < 0.001). Turbidity analysis showed that administration of any of the drugs was associated with higher maximum absorbancy, suggesting thicker fibers, and shorter fibrinolysis time (P < 0.001). Post-treatment reduction in lysis time correlated with an increase in clot porosity in all the groups (r from 0.42 to 0.61; P from 0.01 to 0.001). CONCLUSIONS: Statins, fibrates, and ACEIs may increase plasma clot permeability and susceptibility to fibrinolysis in CAD patients receiving aspirin. This novel antithrombotic mechanism might contribute to clinical benefits of the drugs tested.     

Soma size and oxidative enzyme activity in normal and chronically stimulated motoneurones of the Cat''s spinal cord

In normal adult cats we measured the density of staining for the activity of succinate dehydrogenase (SDH staining) in ventral horn cells of different sizes. The measurements were restricted to that part of the lumbar ventral horn (L6-L7) which is known to contain motoneurones of the peroneal nerve. A statistically significant tendency was found for the SDH staining to be denser in smaller than in larger neurones within the size range of a motoneurones (soma diameter greater than 40 microns). These results are consistent with recently published evidence for ventral horn cells of rats and qualitatively similar relationships between size and SDH staining have also been observed among skeletal muscle fibres (confirmed for mixed muscle of cat in present study). In hindlimb muscles, size as well as SDH staining are known to be markedly activity-dependent. We tested whether this is the case for peroneal motoneurones as well by analyzing the effects of chronic nerve stimulation on the properties of neurones within the appropriate region of the ventral horn. Prior to the final acute experiment, these cats had been subjected to a left-side dorsal rhizotomy and hemispinalization. By aid of a portable mini-stimulator, the left-side common peroneal nerve was activated by repetitive pulses during 50% of total time per day (intra-activity rate: 10, 20 or 40 Hz). After 8 weeks of such treatment, cell sizes as well as the densities of SDH staining showed hardly any differences between peroneal ventral horn cells of the experimental and control sides of the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of the Platelet Glycoprotein Ⅰa C807T Gene Polymorphism With Risk of Myocardial Infarction in Chinese

Objectives To investigate the relationship of the GPIa C807T dimorphism to the risk of myocardial infarction (MI) in Chinese. Methods We did a case-control study including 100 patients and 110 controls with same race. An allele-specific polymerase chain reaction (PCR) was used for genotyping of C807T polymorphism. Results An apparent association was found between the T807 allele and MI among individuals younger than the mean age of 60 years (odds ratio,2.49; 95% confidence interval, 1.08 ～ 6.22 ). The T807 allele remained an independent risk factor for MI when age, sex, smoking, hypertension, diabetes, bodymass index, LDL-cholesterol and HDL-cholesterol were adjusted by logistic regression. Conclusions GPⅠa T807 appears to be an independent risk factor for MI.     

用99Tcm-HL91评价鼠心肌缺血模型

目的 探讨乏氧心肌显像剂99Tcm-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)用于诊断实验性缺血心肌的价值.方法 建立大鼠心肌在体缺血再灌注模型,采用体外放射自显影法检测正常对照组(6只)、缺血再灌注组(8只)及无再灌注组(8只)鼠心肌对99Tcm-HL91的摄取.结果 对照组和无再灌注组心肌未见局灶性放射性浓聚,再灌注组心肌非坏死区有较高放射性浓聚,与正常心肌组织的摄取比值为1.634±0.354.结论 99Tcm-HL91表现出较强的亲乏氧组织特性,能较好区分存活和梗死心肌.     

Comparison of 180° and 360° acquisition for myocardial perfusion SPECT with compensation for attenuation, detector response, and scatter: Monte Carlo and mathematical observer results

BACKGROUND: The optimal projection data acquisition strategy for myocardial perfusion (MP) single photon emission computed tomography (SPECT) remains controversial. METHODS: We compared MP SPECT using 180 degrees and 360 degrees projection data obtained with the same acquisition time, reconstructed either with filtered back projection (FBP) or the iterative ordered-subsets expectation maximization (OS-EM) algorithm with various combinations of attenuation, detector response, and scatter compensation using mathematical observers and a myocardial defect detection task. We used Monte Carlo-simulated projection data from a population of 3-dimensional nurbs-based cardiac-torso (NCAT) phantoms with ranges of variability in patient anatomy, organ uptake, defect location, defect size, and noise level based on clinical data. Projection data from 180 degrees and 360 degrees acquisitions were generated by assuming the same acquisition time. After iterative or FBP reconstruction, standard postprocessing methods were applied. For each acquisition and reconstruction method, we optimized the number of iterations and cut-off frequency of the Butterworth filter using the Channelized Hotelling Observer methodology. The optimum set of parameters was that which gave the maximum area under the curve. RESULTS: For both acquisition protocols, OS-EM with compensations provided better performance than FBP or OS-EM without compensation. For FBP, the optimized 180 degrees acquisition provided a statistically significant increase in AUC as compared with optimized 360 degrees acquisition. For OS-EM, the AUCs for 180 degrees were slightly larger than for 360 degrees acquisitions when comparing images reconstructed with the same compensations. However, the differences were smaller and not statistically significant. CONCLUSION: With optimized reconstruction and filtering parameters, 180 degrees acquisition provided a statistically significant improvement over 360 degrees acquisition for FBP reconstruction. However, for OS-EM the differences were small and not statistically significant.     

IMA在急性冠状动脉综合征中的诊断意义

目的：探讨ACB法检测急性冠脉综合征患者血清中IMA水平及联合检测IMA、CK、CK-MB、cTnI、LDH水平的诊断价值。方法：将80例急性冠脉综合征患者分为3组，不稳定性心绞痛组27例，ST段抬高型心肌梗死组25例，非ST段抬高型心肌梗死组28例，另选150例健康体检者为正常对照组，抽血检测其缺血修饰白蛋白（IMA）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、肌钙蛋白I（cTnI）、乳酸脱氢酶（LDH），对检测结果进行分析讨论。结果：急性冠状动脉综合征3组患者中IMA水平均明显高于正常对照组（P〈0．01），IMA水平以不稳定性心绞痛组最高。各种心肌酶对诊断急性冠状动脉综合征的敏感性分别为：IMA88％、CK22％、CK-MB20％、cTnI32％、LDH28％；CK、CK-MB、cTnI、LDH，四者联合检测敏感性为52％；五者联合检测敏感性可达92％。结论：IMA在早期诊断急性冠脉综合征中具有临床应用价值。ACB法检测IMA对急性冠脉综合征的诊断明显优于其他传统酶类，联合检测则大大提高了急性冠脉综合征的确诊率，减少漏诊和误诊的发生。     

从肝论治急性心肌梗死后心功能障碍的临床研究

目的探讨从肝论治急性心肌梗死（AMI）后心功能障碍的临床疗效。方法68例AMI患者随机分为2组，对照组33例给予单纯西医常规治疗，治疗组35例在对照组治疗基础上，予中药方剂代替血管紧张素转换酶抑制剂（ACEI）和β-受体阻滞剂，每日1剂，水煎服。2组均以2个月为1疗程。应用超声心动图检测2组AMI后15d和1个疗程后的各项心功自岂指标。结果2组AMI后15d的各项心功能指标比较差异无统计学意义（P〉0．05）；1个疗程后，2组二尖瓣前叶振幅（DE）、左室每搏量（SV）、每分钟排血量（CO）、左室射血分数（LVEF）、左室短轴缩短率（FS）、二尖瓣前叶斜率（MVEF）和二尖瓣口多普勒舒张早期最大流速与舒张末期最大流速比率（E／A）均明显改善，平均左室周径缩短率（MVCF）速度加快，左室舒张期及收缩期内径、二尖瓣前叶E峰与室间隔左室面的距离（EPSS）缩小，2组心功能改善情况比较差异有统计学意义（P〈0．05），治疗组优于对照组。结论ACEI和β-受体阻滞剂与中药方剂均能改善AMI后心功能，中药从肝论治优于ACEI和β-受体阻滞剂。     

Evaluation of left ventricular mechanical dyssynchrony as determined by phase analysis of ECG-gated SPECT myocardial perfusion imaging in patients with left ventricular dysfunction and conduction disturbances

Background  Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced systolic heart failure and evidence of dyssynchrony on electrocardiograms. However, a significant percentage of patients do not demonstrate improvement with CRT. Echocardiographic techniques have been used for more accurate determination of dyssynchrony. Single photon emission computed tomography (SPECT) myocardial perfusion imaging has not previously been used to evaluate cardiac dyssynchrony. The objective of this study is to evaluate mechanical dyssynchrony as described by phase analysis of gated SPECT images in patients with left ventricular dysfunction, conduction delays, and ventricular paced rhythms. Methods and Results  A novel count-based method is used to extract regional systolic wall thickening amplitude and phase from gated SPECT images. Five indices describing the phase dispersion of the onset of mechanical contraction are determined: peak phase, phase SD, bandwidth, skewness, and kurtosis. These indices were determined in consecutive patients with left ventricular dysfunction (n=120), left bundle branch block (n=33), right bundle branch block (n=19), and ventricular paced rhythms (n=23) and were compared with normal control subjects (n=157). Phase SD, bandwidth, skewness, and kurtosis were significantly different between patients with left ventricular dysfunction, left bundle branch block, right bundle branch block, and ventricular paced rhythms and normal control subjects (all P<.001) Peak phase was significantly different between patients with right ventricular paced rhythms and normal control subjects (P=.001). Conclusions  A novel SPECT technique for describing left ventricular mechanical dyssyn-chrony has been developed and may prove useful in the evaluation of patients for CRT. This study was funded in part by a research grant from the Medtronic-Duke Strategic Alliance, of which Dr Borges-Neto is the primary investigator.     

上海地区汉族优秀游泳运动员ACE基因I/D多态性研究

目的:探讨上海地区汉族不同水平优秀游泳运动员ACE(血管紧张素转化酶)基因I/D多态性的分布特点。方法:采用PCR方法,对上海地区85名汉族优秀游泳运动员和90名汉族普通人的ACE基因I/D多态性进行检测。结果显示,上海地区汉族优秀游泳运动员的ACE基因的基因型和等位基因频率与上海和成都地区汉族普通人无明显差异(P>0.05);上海地区汉族游泳运动员和普通人以及成都地区汉族普通人的基因型和等位基因频率均与高加索人群存在高度显著性差异(P<0.0001),表现出明显的种族差异性。7名上海地区汉族国际健将ACE基因均为II型,运动水平越高的组别,II基因型和I等位基因频率越高,提示具有II基因型或I等位基因频率高的运动员经过多年运动训练,具有成为优秀运动员的可能,特别是II基因型的运动员可能性更大。     

血管紧张素转换酶2与糖尿病肾病

The identification of angiotensin-converting enzyme (ACE)2 opened new recognition of renin-angiotensin system (RAS). ACE2 degrades Ang Ⅱ to Ang (1-7), maintains homeostasis of RAS with ACE. Studies have revealed that ACE2 has important functions in diabetic nephropathy. It may be a target for drug and is used as gene therapy for diabetic nephropathy. Amplifying ACE2 activity may have a potential therapeutic role for diabetic nephropathy.