钙调神经磷酸酶参与心衰患者心肌重构的信号转导

目的：探讨血管紧张素Ⅱ(Ang Ⅱ)介导的钙调神经磷酸酶（CaN）信号通路参与心力衰竭（CHF）患者心肌重塑的机制。方法:选择因瓣膜性心脏病接受二尖瓣置换术的CHF病人39例，正常对照38例(其中8例来自意外伤亡的器官捐献者)。彩色多普勒超声心动图仪检测心脏扩大和心功能参数。放免法检测血浆及心肌组织Ang Ⅱ浓度，免疫沉淀法测心肌组织CaN、活化T细胞核因子(NFAT₃）、锌指转录因子(GATA₄)磷酸化及蛋白表达，RT-PCR检测肌球蛋白重链（β-MHC）mRNA表达。结果:AngⅡ分别与心脏扩大参数呈显著正相关，而与心功能参数呈显著负相关。CHF患者心肌组织CaN蛋白表达、CaN磷酸化、GATA^₄蛋白表达及β-MHC mRNA表达明显高于对照组，随心功能恶化其表达逐渐增加；NFAT₃磷酸化随心功能恶化而减弱。结论：肾素血管紧张素系统（RAS）激活的CaN信号通路在CHF患者心肌重构机制中可能起重要作用。     

Recovery of hypertrophied rat hearts after global ischemia and reperfusion at different perfusion pressures

The ability to resist transient ischemia was studied in isolated hearts of 18 months old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Both types of hearts showed optimal performance during the preischemic period when perfused at a diastolic perfusion pressure of 8.0 (WKY) and 13.3 (SHR) kPa. Hemodynamic recovery of WKY hearts during reperfusion at 8.0 kPa, following 45 min global ischemia, was satisfactory. Coronary perfusion completely normalized, contractility (dP _lv/dt _max) was slightly depressed and cardiac output returned, on the average, to 40% of the preischemic values. In contrast, hemodynamic function of SHR hearts reperfused at 13.3 kPa was greatly depressed, as evidenced by almost complete abolition of cardiac output, severe reduction ofdP _lv/dt _max and persistent underperfusion of the endocardial layers. In addition, the postischemic release of lactate dehydrogenase was retarded and enhanced. The release patterns of degradation products of adenine nucleotides showed a shift to the endstage produets xanthine and uric acid. The enhanced vulnerability of the hypertrophied heart to ischemia was even more expressed when the SHR hearts were reperfused at 8.0 kPa. Postischemic function was characterized by electrical instability, loss of contractility and cardiac output, and noreflow in the endocardial layers. Persistent accumulation of lactate and degradation products of adenine nucleotides in the postischemic hearts are in line with the lack of reperfusion. The present results indicate that a detailed mechanistic explanation for the reduced ability to withstand ischemia of SHR cannot be based on differences in ATP content or an altered anaerobic glycolitic activity prior and during ischemia. It is suggested that a defect on the circulatory level, probably caused by enhanced reactivity of the coronary vessels towards ischemia-elicited factors, is responsible for the higher vulnerability of hypertrophied heart to an ischemia insult.Supported by Medigon/NWO (grant number 900516091)     

聪灵胶囊对小鼠软脑膜微循环障碍的改善作用

目的 观察聪灵胶囊对小鼠软脑膜微循环障碍的改善作用。方法 将60只小鼠随机分为聪灵胶囊大、中、小剂量组、阳性对照组和正常对照组，分别于灌胃给药10d后，开颅窗观察小鼠软脑膜微循环，然后在软脑膜局部滴加去甲肾上腺素复制微循环障碍模型，观察微循环障碍时小鼠软脑膜微循环。结果 聪灵胶囊各剂量组均可改善去甲肾上腺素所致的小鼠软脑膜局部微循环障碍．使微动脉扩张，血流增快，每视野交织网点数增多，对血流流态也有一定的改善作用，使血色变红。9min后聪灵胶囊各剂量组软脑膜局部微循环障碍基本恢复，而空白对照组恢复不明显。结论 聪灵胶囊能改善小鼠软脑膜微循环。     

高雌激素血症对雌性心肌梗塞大鼠心肌舒缩性能的影响

本文研究了高雌激素血症对雌性心肌梗塞(MI)大鼠心肌舒缩性能的影响。结果:(1)MI组血浆雌二醇(E_2)先略升高而后降低,雌二醇处理MI组(MIE_2)血浆雌二醇明显升高。(2)MIE_2组心肌纤维直径比对照假手术组(CS)及MI组显著增大(10.65±0.59 VS 7.65±0.40及10.15±0.54gm,P<0.001,<0.02)。(3)两MI组的LVSP、±dp/dt max均显著降低,T-值明显延长,尤以MIE_2组更为显著(10.5±4.1 VS 6.2±4.6ms,P<0.02)。(4)两MI组动脉压显著降低,HR减慢,LVET延长;在9天观测点,MIE_2组的HR仍较MI组显著减慢、LVET明显延长。提示高雌激素血症可使雌性心肌梗塞大鼠心肌舒缩性能降低。     

Myokardiale Aufnahme von Lidocain,Mexiletin und Amiodaron nach Akutapplikation

Summary To assess acute myocardial uptake of antiarrhythmic drugs, we measured drug concentrations simultaneously in the aorta and in the coronary sinus during diagnostic cardiac catheterization. Measurements were taken 1, 2, 3, 4, 5, 7, and 10 minutes after intravenous bolus application of lidocaine (n= 10, 25 mg), mexiletine (n= 5, 25 mg andn= 10, 100 mg), or amiodarone (n= 10, 25 mg). Drug levels were measured by high-pressure liquid chromatography. Maximal concentrations were observed after 2–5 min. After 3–5 min coronary sinus levels exceeded aorta levels, indicating the end of net myocardial drug uptake. In contrast to lidocaine and amiodarone, no mexiletine was found in the coronary sinus 15 s after the end of drug application, obviously indicating a high myocardial drug content. Furthermore, the data provide an explanation for the acute efficacy of amiodarone. The myocardial uptake may result in various pharmacodynamic effects of antiarrhythmic drugs.

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deAbkürzungen Art. Arteria - min Minuten - s Sekunden - i.v. intravenös Mit Unterstützung der Deutschen Forschungsgemeinschaft (Ni 241/1–2)     

Prognosis of patients with different peak serum creatine kinase levels after first myocardial infarction

The extent to which patients with low peak serum creatine kinase(CK) at their first myocardial infarction differ from patientswith high CK levels in terms of risk for subsequent ischaemicevents was investigated in 266 patients who survived the first48 h from the onset of infarction. All patients were followedup for one year. Four groups were formed based on peak CK200,201–400, 401–800 and >800 IU l^-1. During follow-upthe incidence of mortality was 15% (N=39), non-fatal re-infarction9% (N=23), and angina 53% (N=140). Hospital mortality was significantlyhigher (P<0.02) in the highest CK-group (16%), but the incidenceof non-fatal re-infarction, angina pectoris and late mortalitywas similar in the four groups. In hospital survivors, ischaemicST-changes during pre-discharge symptom limited bicycle stresstest and multiple vessel disease were equally distributed inall four groups. We conclude that while hospital mortality is directly relatedto peak CK, there is no relationship between peak CK and latemortality, non-fatal re-infarctions, or recurrent angina. Accordingly,diagnostic and therapeutic procedures in the individual patientsare notinfluenced by the amount of serum CK released duringacute infarction.     

Effect of 3-methyl-branching on the metabolism in rat hearts of radioiodinated iodovinyl long chain fatty acids

The metabolism of two new 3-methyl-branched iodovinyl fatty acids in rat hearts was evaluated by determining the subcellular and lipid pool distribution of these radiolabeled analogues after intravenous injection. Methyl branching had been introduced into the straight chain analogue, 19-iodo-18-nonadecenoic acid (IVN), to produce the monomethyl analogue, 19-iodo-3-(R,S)-methyl-18-nonadecenoic acid (BMIVN) and the dimethyl derivative, 19-iodo-3,3-dimethyl-18-nonadecenoic acid (DMIVN) in the hope of inhibiting oxidation. Since the presence of 3-methyl branching results in delayed myocardial clearance in rats, differences were sought in the lipid and subcellular distribution of these branched analogues that might correlate with the prolonged retention and reflect differences in metabolism. Hearts of rats injected intravenously with the radiolabeled fatty acids were removed and homogenized and the homogenates partitioned between the chloroform-methanol (organic) fraction and the aqueous fraction. Comparison of the distribution of radioactivity between the organic and aqueous fractions showed that most of the DMIVN and BMIVN activity was in the organic fraction with IVN activity initially divided equally between the two fractions. Identification of the lipid components of these organic fractions showed that there was slow incorporation of DMIVN into the triglyceride and polar lipid fractions with a slow loss from the free fatty acid fraction. With the straight chain IVN analogue which shows rapid washout from rat hearts, there was loss of activity from all 3 lipid components during the 60 min. The monomethyl branched BMIVN analogue demonstrated predominant storage in the polar lipid fraction with some incorporation into triglycerides. Subcellular distribution studies of the three analogues also showed differences that correlated with the observed differences in heart retention properties. With the unbranched IVN analogue, radioactivity was found primarily in the cytoplasmic fraction 30 min after injection, whereas the branched analogues demonstrated a much higher association with the microsomal and mitochondrial fractions of the heart. In rats fed prior to injection, these differences in the subcellular distribution profiles were minimized. The lipid and subcellular distribution patterns reported here for the methyl branched analogues as compared to those of the straight chain iodovinyl fatty acid may provide some understanding as to the mechanisms of retention in rat myocardium.Research supported by the Office of Health and Environmental Research, U.S. Department of Energy, under contract DE-AC0 5-840 R21400 with Martin Marietta Energy Systems, Inc.     

Infection of cardiac mural thrombus associated with left ventricular aneurysm

Infection is a rare complication of cardiac mural thrombus andmay prove difficult to diagnose and treat. We describe a patientwith infected thrombus associated with a left ventricular aneurysm,involving Salmonella typhimurium. Cross-sectional echocardiographyproved helpful in establishing the diagnosis.     

超声彩色室壁动力学对心肌梗死范围定量的实验研究

目的验证超声彩色室壁动力学(CK)分析技术判断心肌梗死的准确性.方法结扎犬冠状动脉(冠脉)造成实验性急性心肌梗死模型,应用超声CK分析技术与病理解剖的结果进行对比性研究.结果结扎犬冠脉前超声CK图像由红-黄-绿-蓝色组成,色彩分布均匀,心内膜彩色移位(SEM)值为7.98～14.53mm结扎犬冠脉后造成实验性急性心肌梗死时超声CK图像绿-蓝色完全消失,仅遗留红-黄色,SEM值为1.27～6.45mm,与结扎前对比明显减少(P<0.05).超声CK图像检测的心肌梗死范围为(26.2±4.8)mm2,病理解剖测量为(22.5±4.7)mm2,两者对比显著相关(r=0.9264,P<0.01).结论超声CK图像有助于急性心肌梗死定性、定量诊断.     

磷酸肌酸停搏液对缺血心肌的保护作用

目的 探讨外源性磷酸肌酸（creatine phosphate,CP）在心脏直视手术中作为添加剂加入心脏停搏液中对缺血心肌的保护作用。方法 66例接受心内直视手术的患者分为对照组（I组）及试验组（Ⅱ组）,各33例。I组使用冷晶体停搏液,Ⅱ组在I组停搏液中加入CP。于不同时段取血样检测5种心肌酶的含量。结果 两组心肌酶含量,术前差异无显著性;术后Ⅱ组心肌酶谱上升幅度低于I组,而下降速度则快于I组。结论 外源性CP加入心脏停搏液中对心肌具有良好的保护作用。