Mass fragmentographic determination of myocardial free fatty acids

In contrast to plasma free fatty acids (FFA) remarkably little work has been carried out on myocardial FFA content directly. Reported values of normal FFA content vary so widely (29.0 to 25 000 nmol/g wet wt) that clearly the usual methods for the determination of FFA are difficult or not at all applicable to myocardial tissue. A method has been developed for the mass fragmentographic determination of myocardial FFA content and distribution and has been validated for sensitivity, reproducibility, specificity, recovery, cross-reaction with other lipids and reliability.The FFA content of normoxic canine myocardium was found to be 55.6 ± 20.2 nmol/g wet wt. This value is considerably below most of the previously reported values and much of the reported work on myocardial FFA content and changes must be re-examined.     

Effects of the Na+ antagonist cibenzoline on left ventricular function of postischemic hearts

Summary The negative inotropic effect of antiarrhythmic drugs is a major drawback in antiarrhythmic drug therapy, especially in patients with reduced contractile function of the left ventricle. The circulatory and myocardial effects of the new class I antiarrhythmic drug (a Na⁺ antagonist), cibenzoline (2 mg/kg i.v.), were investigated in 47 open-chest rats with normal and postischemic myocardium (3×4 minutes of global ischemia). Hemodynamic measurements in the intact circulation and isovolumic registrations (peak isovolumic left ventricular systolic pressure and peak isovolumic dP/dt_max) were compared to saline controls. In rats with postischemic myocardium, cibenzoline caused a significant (p<0.001) decrease in the cardiac output for 38%, in the dP/dt_max for 30%, and in the peak isovolumic dP/dt_max for 19% at the end of infusion (compared to the control). The heart rate was reduced by 22% (p<0.001), the mean aortic pressure by 22% (p<0.001), and the calculated systemic resistance by 20% (p<0.001). In contrast to the results with postischemic myocardium, no important changes in the hemodynamics were detectable after an identical dose in normal animals without left ventricular dysfunction. The results indicate that standard doses of the Na⁺ antagonist cibenzoline may induce significant cardiodepressant effects on postischemic left ventricles with reduced function.     

急性心肌梗死后存活心肌对梗死相关血管晚期血运重建术后左室功能的影响

目的探讨存活心肌对急性心肌梗死(AMI)后梗死相关血管(IRA)晚期血运重建术后远期左室功能以及左室重构的影响.方法69例AMI未接受早期再灌注治疗者,于发病10～21 d行IRA经皮冠状动脉血运重建(PCI)术,术前于AMI发病后5～10 d应用小剂量多巴酚丁胺(5和10μg·min-1·kg-1)超声心动图负荷试验检测存活心肌,并分别测定和计算给药前后左室腔大小、左室射血分数(LVEF)以及室壁运动积分(WMS).按有无存活心肌分为存活心肌组和无存活心肌组,超声心动图随访术后6个月时两组左室腔大小、LVEF和WMS的变化.结果157个运动异常节段中89个节段(57%)有存活心肌,有存活心肌组26例(占38%),无存活心肌组43例(占62%).存活心肌组术后6个月LVEF较术前明显提高(P＜0.05),收缩末期容积指数(LVESVI)和WMS明显降低(P＜0.05和P＜0.01);而无存活心肌组LVEF较术前明显降低(P＜0.01),LVESVI和左室舒张末期容积指数(LVEDVI)较术前明显增加(P＜0.05),WMS无明显变化.存活心肌组多巴酚丁胺负荷时的LVEF和WMS明显改善,且与6个月时的测定值相近;而无存活心肌组PCI前应用多巴酚丁胺LVEF和WMS均无明显变化.结论AMI后有存活心肌者晚期血运重建有利于改善远期左室功能和减少左室重构.心肌梗死后早期小剂量多巴酚丁胺负荷状态下左室收缩功能的提高预示晚期血运重建术后心功能改善.     

Effects of selenium deficiency on the rat myocardial protein pattern – investigation by two-dimensional gel electrophoresis

Dietary selenium deficiency represents an etiological factor in “Keshan disease”, a distinct form of an endemic cardiomyopathy. The biochemical effects of selenium depletion in the myocardium are, however, not yet known. Therefore, we investigated the changes in the myocardial protein pattern in rats after long-term selenium deficiency. The myocardial proteins were analyzed in samples from five selenium-depleted rats (Se-deficient group) and five rats supplied with adequate amounts of the element (Se-adequate group). Isoelectric focusing (IEF) with carrier ampholytes on large 2-DE gels was used for the separation of proteins in the first dimension and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) for the second dimension. The protein patterns were evaluated by means of a computer-assisted gel analysis system. The biochemical identification of the proteins of interest was achieved by matrix-assisted laser desorption/ionization mass spectrometry (MALDI) or immunoblotting. On average, 588 ± 68 protein spots were found on the gels. No significant difference in spot numbers existed between the groups. A pattern of 270 spots with identical positions was found on every gel; 247 of these spots were not saturated and used for quantitative comparison. Thirty-five, i. e., 14%, differed significantly in their relative intensity in the two groups. Twenty-eight protein spots were decreased in the Se-deficient group and seven were increased. Sarcomeric creatine kinase M chain, α-myosin heavy chain (α-MHC) and myosin light chain 1 and 2 (MLC 1 and 2) were largely decreased in Se-deficiency. Three protein spots were increased by more than twofold or appeared only in the Se-deficient group. A mitochondrial creatine kinase was identified in this group. The results suggest that selenium deficiency affects myocardial energy metabolism and contractile proteins. These changes probably reflect non-specific alterations in heart failure. Received: 19 February 1997, Returned for 1. revision: 7 April 1997, 1. Revision received: 29 January 1999, Returned for 2. revision: 18 February 1999, 2. Revision received: 21 December 1999, Accepted: 6 January 2000     

丹参酮Ⅱ A对左心室肥厚的逆转作用及其机制

目的 研究丹参酮Ⅱ A对大鼠腹主动脉缩窄术后左室肥厚心肌的作用及一氧化氮的影响.方法 SD大鼠行腹主动脉缩窄术建立高血压左室心肌肥厚模型,术后4周将手术大鼠随机分为假手术组、未治疗左室肥厚(LVH)组、丹参酮低剂量组[10 mg/(kg·d),腹腔注射]、丹参酮高剂量组[20 mg/(kg·d),腹腔注射]及缬沙坦组[10 mg/(kg·d),灌胃],每组各8只.用药8周后通过超声心动图测定左室后壁、室间隔的厚度;取左心室组织检测左心室质量指数(LVMI)、病理切片HE染色测量心肌纤维直径(MFD);硝酸还原法测定心肌组织NO的含量、免疫印迹法(Western blot)检测蛋白激酶C(PKC)蛋白的表达.结果 腹主动脉缩窄术后,SD大鼠血压明显升高,出现左心室肥厚.缬沙坦可降低大鼠的血压[(136±15)mm Hg]并减轻左心室肥厚.低剂量、高剂量丹参酮组与LVH组相比虽不能降低血压[(188±11)、(187±14)mm Hg vs(186±13)mm Hg,P＞0.05],但能明显减低左室后壁、室间隔厚度、LVMI、MFD值(P＜0.01),同时可使心肌的NO明显增加[(12.8±1.7)、(12.0±1.4)vs(5.8±1.1)μmol/g,P＜0.01],心肌PKC蛋白的表达明显下调[(0.605±0.051)、(0.519±0.062)vs(1.291±0.117),P＜0.01].结论 丹参酮对心肌肥厚的逆转作用是非血压依从性的,丹参酮Ⅱ A可能通过促进心肌局部NO的产生、抑制PKC蛋白的表达起到阻止、逆转高血压心肌肥厚的发展.     

Altered hypoxia‐inducible factor‐1 alpha expression levels correlate with coronary vessel anomalies

The outflow tract myocardium and other regions corresponding to the location of the major coronary vessels of the developing chicken heart, display a high level of hypoxia as assessed by the hypoxia indicator EF5. The EF5‐positive tissues were also specifically positive for nuclear‐localized hypoxia inducible factor‐1 alpha (HIF‐1α), the oxygen‐sensitive component of the hypoxia inducible factor‐1 (HIF‐1) heterodimer. This led to our hypothesis that there is a “template” of hypoxic tissue that determines the stereotyped pattern of the major coronary vessels. In this study, we disturbed this template by altering ambient oxygen levels (hypoxia 15%; hyperoxia 75–40%) during the early phases of avian coronary vessel development, in order to alter tissue hypoxia, HIF‐1α protein expression, and its downstream target genes without high mortality. We also altered HIF‐1α gene expression in the embryonic outflow tract cardiomyocytes by injecting an adenovirus containing a constitutively active form of HIF‐1α (AdCA5). We assayed for coronary anomalies using anti‐alpha‐smooth muscle actin immunohistology. When incubated under abnormal oxygen levels or injected with a low titer of the AdCA5, coronary arteries displayed deviations from their normal proximal connections to the aorta. These deviations were similar to known clinical anomalies of coronary arteries. These findings indicated that developing coronary vessels may be subject to a level of regulation that is dependent on differential oxygen levels within cardiac tissues and subsequent HIF‐1 regulation of gene expression. Developmental Dynamics 238:2688–2700, 2009. © 2009 Wiley‐Liss, Inc.     

心肌酶谱及其比值与肌钙蛋白定量测定对儿童病毒性心肌炎的诊断价值

目的初步了解重庆市主城区儿童心肌酶的正常范围,探讨其比值及肌钙蛋白Ⅰ(cTnI)测定对儿童病毒性心肌炎的诊断价值。方法采用OLYMPUS 400全自动生化分析仪测定肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、α-羟丁酸(αHBDH)并计算出CK-MB/CK、αHBDH/LDH比值;CK采用酶耦联测定法,αHBDH、LDH采用连续监测法,CK-MB采用免疫抑制法,cTnI采用胶乳增强免疫比浊法测定。结果 200名健康儿童心肌酶水平均高于健康成人(P<0.01),但不同组别CK-MB/CK<0.03者占80%以上,αHBDH/LDH在0.7～0.9之间占85%以上。80名健康儿童运动后的心肌酶普遍高出儿童正常范围,但其比值并未升高。已确诊的132例儿童病毒性心肌炎患者中心肌酶异常者107例(占80%),CK-MB/CK>0.07者80例,αHBDH/LDH>0.9者78例,cTnI结果阳性90例。其比值和cTnI结果经配对检验存在一致性关联。结论不能用成人的标准来判断儿童心肌酶异常,儿童心肌酶单项升高不能作为病毒性心肌炎的诊断依据;CK-MB/CK>0.07、αHBDH/LDH>0.9以及cTnI结果阳性对诊断病毒性心肌炎有极大的临床价值。     

氨甲酰化促红细胞生成素逆转慢性心力衰竭大鼠心肌重塑的作用

目的:观察血清基质金属蛋白酶-2(Matrix metalloproteinase-2, MMP-2)及其组织抑制因子(Tissue inhibitor of metalloproteinase-1, TIMP-1)水平与心肌胶原容积指数(CVF)的变化,探讨氨甲酰化促红细胞生成素(CEPO)对慢性心力衰竭(CHF)心肌重塑的作用及其机制.方法:从80只Wistar雄性大鼠中随机选取10只作为对照组,其余腹腔注射异丙肾上腺素建立CHF模型.5周后将造模成功的大鼠再随机分为2组:CHF组(n=18);CEPO组(n=18),腹腔注射CEPO 50 μg/kg,2次/周,连续4周.CHF组和对照组同期腹腔注射等量0.9%氯化钠溶液.4周后检测3组大鼠血流动力学指标、左心室重量指数(LVMI)和血清MMP-2及TIMP-1水平与CVF的变化.结果:与对照组相比,CHF组左室收缩压(LVSP)、左室内压上升/下降最大速率(±dp/dtmax)绝对值均显著降低(P<0.01),左室舒张压(LVDP)、左室舒张末压(LVEDP)升高(P<0.01),血清MMP-2升高(P<0.01)而TIMP-1降低(P<0.01),LVMI及CVF升高(P<0.01);与CHF组相比,CEPO组大鼠血流动力学各指标变化均有显著差异(P<0.01),血清MMP-2水平降低(P<0.01)、TIMP-1水平升高(P<0.01),LVMI及CVF降低(P<0.01).结论:CEPO有明确的抗心力衰竭作用,通过调节MMP-2和TIMP-1的表达,降解细胞外基质胶原含量,逆转心肌重塑,从而改善心脏功能.     

冠脉内注射替罗非班对急性心肌梗死急诊介入治疗ST段回落的影响

目的:应用ST段回落指数观察冠脉内负荷替罗非班对急性心肌梗死直接经皮冠状动脉介入治疗的有效性和安全性。方法:选择因急性ST段抬高心肌梗死入院,并接受直接急诊经皮冠状动脉介入治疗患者92名,分为试验组(冠脉内负荷替罗非班+PCI)42例和对照组(静脉负荷替罗非班+PCI)50例。观察两组术后心电图ST段回落指数,PCI术前、术后TI-MI血流情况,术后30天射血分数(EF),30天主要心血管事件(心绞痛,再次心肌梗死和死亡)。结果:试验组术后2h、4h、8h心电图ST段回落指数均高于对照组(P<0.05),两组PCI术前梗死相关血管各级TIMI血流与对照组无显著性差异。试验组PCI术后即刻达TIMI 3级血流比例高于对照组(P<0.05),PCI术后30分钟达到TIMI 3级血流比例也显著高于对照组(P<0.05),试验组30天心脏射血分数高于对照组(P<0.05),试验组30天内主要心血管事件(心绞痛+再次心肌梗死+死亡)的发生率较对照组降低66.00%(P<0.05)。两组间所有出血相关并发症无显著性差异(P>0.05)。结论:ST段回落指数能有效评价急性心肌梗死急诊经皮冠状动脉介入治疗后心肌损伤程度,是最简单易行的评估方法;冠脉内负荷替罗非班在急性心肌梗死直接经皮冠状动脉介入治疗中改善术后心肌灌注,降低心血管事件,并不增加出血的风险。