卡维地洛与美托洛尔治疗心力衰竭的疗效对比观察

目的:比较卡维地洛与美托洛尔治疗充血性心力衰竭(CHF)的疗效及对神经激素、细胞因子的影响。方法:选择CHF患者120例,随机分3组。A组为对照组:予以血管扩张剂、利尿剂、地高辛等常规心力衰竭治疗。B、C组在上述治疗基础上分别予以美托洛尔50mg,bid、卡维地洛25mg,bid口服,维持该剂量至6个月。用药前后分别观察左室射血分数(LVEF)、每搏输血量(SV)、短轴缩短率(FS)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、相对室壁厚度(RWT)及醛固酮(ALD)、肿瘤坏死因子-α(TNF-α)、内皮素(ET)、心钠素(ANP)等指标变化情况。结果:6个月后B组及C组LVEDD、LVESD缩小,RWT增厚,LVEF、FS、SV明显提高,而ALD、ET、TNFα、ANP水平明显降低,与治疗前及A组比较均差异有统计学意义。B、C组再入院率及病死率均明显低于A组,同时C组LVEF改善优于B组。结论:美托洛尔、卡维地洛均可明显降低CHF患者神经激素、细胞因子的水平,逆转心室重塑,改善心脏功能。卡维地洛疗效及耐受性略优于美托洛尔。     

Coordinate Regulation of Metabolic Enzyme Encoding Genes During Cardiac Development and Following Carvedilol Therapy in Spontaneously Hypertensive Rats

Fuel substrate utilization is highly regulated during cardiac development and with the onset of cardiac hypertrophy. Glucose and lactate are the predominant fuel substrates utilized during cardiac development. Postnatally, a switch occurs so that fatty acids become the chief energy substrate in the nonfed adult mammalian heart. A reversion back towards fetal energy metabolism occurs with the development of cardiac hypertrophy. To evaluate the role of this substrate preference switch in the development of cardiac hypertrophy, the molecular regulation directing these switches is being explored. Thus, we have begun by defining the temporal expression patterns of genes encoding key rate-controlling enzymes directing major fuel substrate metabolism during cardiac development, with pressure-overload-induced cardiac hypertrophy, and following antihypertensive therapy in spontaneously hypertensive rats. The genes encoding the fatty acid and adult enriched rate-controlling glycolytic enzymes are expressed at low levels in the fetal and neonatal rat heart. The genes encoding these enzymes are significantly and coordinately upregulated ( 70%) in adult rat hearts compared to the fetal expression patterns. A reciprocal and coordinate downregulation ( 40% reduction) of the fatty acid and adult enriched glycolytic enzyme encoding genes are observed with the induction of pressure-overload-induced hypertrophy in spontaneously hypertensive rats compared to Wistar–Furth normotensive control rats. Antihypertensive therapy with carvedilol, a vasodilating -and -adrenoreceptor antagonist, attenuates this reversion of the metabolic gene expression pattern towards fetal levels compared to placebo-treated littermate controls. This coordinate developmental and hypertrophy-induced regulation of genes that encode enzymes controlling both fatty acid and glycolytic catabolic pathways in the heart implicates potential mutual/overlapping regulatory signaling proteins within their gene regulatory programs. These gene regulatory pathways need to be identified and modulated in order to characterize the functional role of fuel substrate metabolism in cardiac development and with the induction of cardiac hypertrophy.     

卡维地洛治疗心力衰竭的疗效观察

目的 观察卡维地洛对充血性心力衰竭(CHF)的临床疗效。方法 将52例CHF患者随机分为卡维地洛组和常规治疗组，卡维地洛组在常规抗心衰治疗的基础上给予卡维地洛；常规治疗组采用安慰剂加常规抗心衰治疗。结果 卡维地洛治疗5个月后心功能及超声指标与常规治疗组相比均明显改善。结论 卡维地洛对充血性心力衰竭的治疗有显著效果。     

卡维地洛对冠心病心力衰竭患者心室重构和心功能的影响

目的　探讨卡维地洛对冠心病心力衰竭患者心室重构及心功能的影响。方法　冠心病心力衰竭患者 80例 ,左室射血分数≤ 45 % ,心功能Ⅱ～Ⅲ级 ,常规治疗基础上随机分为治疗组和对照组 ,治疗 6个月 ,观察卡维地洛对心室重构、心功能的影响。结果　经过 6个月治疗 ,与对照组相比 ,卡维地洛组左室射血分数明显升高 (P <0 .0 1) ,左室收缩末容量指数、左室舒张末容量指数、左室重量指数均显著降低 (P <0 .0 1)。结论　在常规治疗的基础上 ,应用卡维地洛能显著改善冠心病心力衰竭患者的心功能 ,改善心室重构     

曲美他嗪辅助卡维地洛治疗高血压性心脏病的疗效及对p38MAPK水平的影响

目的 探究曲美他嗪辅助卡维地洛治疗高血压性心脏病的疗效及对p38MAPK水平的影响。方法 选择开封市祥符区中医院2016年10月-2018年10月收治的高血压性心脏病患者106例为研究对象,根据其入院顺序经随机数字表法分为两组,每组53例。其中,对照组给予卡维地洛进行治疗,观察组在对照组基础上联合曲美他嗪进行治疗,对比两组患者的超声心动图测定各指标、血压变化和血清TNF-α、IL-6、p38MAPK水平。结果 治疗前,两组患者的左室射血分数（LVEF）、左室舒张末期内径（LVDD）、左室收缩末期内径（LVSD）、左房内径（LAD）、室间隔厚度（IVST）水平对比无显著性差异;治疗后,两组患者的LVDD、LVSD、LAD、IVST水平均比治疗前显著降低（P<0.05）,且观察组显著低于对照组（P<0.05）;治疗后,两组患者的LVEF水平均比治疗前显著升高（P<0.05）,且观察组显著高于对照组（P<0.05）。治疗前,两组患者的收缩压（SBP）、舒张压（DBP）水平对比无显著性差异;治疗后,两组患者的SBP、DBP水平均比治疗前显著降低（P<0.05）,且观察组显著低于对照组（P<0.05）。治疗前,两组患者的血清肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）、P38丝裂原活化蛋白激酶（p38MAPK）水平对比无显著性差异;治疗后,两组患者的血清TNF-α、IL-6、p38MAPK水平均比治疗前显著降低（P<0.05）,且观察组显著低于对照组（P<0.05）。结论 曲美他嗪辅助卡维地洛治疗高血压性心脏病的效果显著,该方法可有效降低患者的血压水平和炎症因子水平,并抑制p38MAPK活化,临床应用效果显著。     

Carvedilol,A Novel Cardiovascular Agent,Inhibits Development of Vascular and Ventricular Hypertrophy in Spontaneously Hypertensive Rats

The effects of carvedilol, a novel cardiovascular agent, were evaluated in developing spontaneously hypertensive rats (SHR) for effects on hemodynamics, and the ability to effect the development of left ventricular, and vascular hypertrophy associated with chronic hypertension. Chronic oral administration of low dose carvedilol (20 mg/kg/day) was initiated when rats were 5 weeks of age, and experiments progressed until 14 weeks of age. Carvedilol-treated SHR had significantly reduced systolic blood pressures and heart rates throughout the duration of the experiment, and had significantly reduced ventricle/body weights by approximately 9.0%. Morphologic analysis of tertiary branches of the mesenteric artery revealed that carvedilol-treated     

心衰大鼠心肌细胞凋亡的变化及卡维地洛对其干预的作用

目的　了解心肌细胞凋亡在充血性心力衰竭 (Congestiveheartfailure ,CHF)发生、发展中的作用 ,探讨卡维地洛(Carvedilol ,CAR)治疗CHF的作用机制。方法　观察雄性Wistar大鼠心肌梗塞 (Myocardialinfarction ,MI)后的血流动力学参数、心室重塑指标、心肌细胞凋亡、心肌总抗氧化能力和丙二醛的改变 ,并于MI后 1周对大鼠进行 7周的CAR和美托洛尔 (MET)干预 ,观察CAR和MET对上述指标的影响。结果　MI后 4周大鼠动脉压、±dp/dtmax和心肌总抗氧化能力下降 ,左室舒张末压、右室 /体重比及丙二醛增高 ,MI后 8周上述改变更为明显 ;MI后心肌细胞凋亡指数逐渐升高 ;CAR和MET可不同程度地改善心功能指标 ,CAR降低心肌细胞凋亡指数、丙二醛及升高总抗氧化能力的效果优于MET。结论　心肌细胞凋亡在MI后CHF发生、发展过程中起着重要的作用 ,氧化应激是介导心肌细胞凋亡的主要刺激因素。CAR可有效地减少MI后心肌细胞凋亡、防治CHF ,这与其强大的抗氧化作用有关     

卡维地洛对兔颈动脉易损斑块与血管平滑肌细胞凋亡及基因表达的影响

目的探讨动脉易损斑块(VP)与血管平滑肌细胞(VSMC)凋亡的关系及卡维地洛稳定斑块的作用机制。方法将45只雄性日本大耳白兔随机分成5组,分别为正常对照组、卡维地洛组、美托洛尔组、单纯转染组和单纯拉伤组,每组9只。正常对照组给予普通饲料,其他组给予球囊损伤颈总动脉加高脂喂养,8周后,除单纯拉伤组,其他3组给予野生型p53基因转染颈总动脉,卡维地洛组和美托洛尔组分别加喂卡维地洛和美托洛尔,继续高脂饲料喂养4周;实验前、实验后8、12周分别测定血脂;实验结束后检测斑块VSMC凋亡率及bcl-2、bax、α平滑肌肌动蛋白(-αactin)的局部表达情况,并分析血管病理形态学。结果球囊损伤组均出现典型动脉粥样硬化斑块,与单纯转染组比较,美托洛尔组及卡维地洛组纤维帽厚度均明显增加,卡维地洛组更显著(P<0.01);卡维地洛和美托洛尔对血脂均无明显影响;卡维地洛组斑块中VSMC凋亡率、bax及bax/bcl-2比值下降,上调-αactin、bcl-2阳性表达(P<0.01)。结论卡维地洛稳定斑块作用优于美托洛尔,其机制可能在于卡维地洛除β受体阻断作用外还具有抑制VSMC凋亡的作用。