伊贝沙坦与雷米普利对充血性心力衰竭疗效比较

目的比较伊贝沙坦与雷米普利对充血性心力衰竭(CHF)的临床疗效及安全性。方法72例CHF患者在常规治疗基础上随机分为2组。伊贝沙坦组(36例)口服伊贝沙坦150 mg.d-1;雷米普利组(36例)口服雷米普利2.5 mg.d-1。治疗前与治疗6 mo后分别用超声心动图测量左室射血分数(LVEF)、左室短轴缩短分数(LVFS)、每搏输出量(SV)、心排量(CO)、心脏指数(CI)评估心功能。结果治疗6 mo后,2组心功能较治疗前非常明显改善(P<0.01),2组之间比较差异无统计学意义(P>0.05)。结论伊贝沙坦与雷米普利治疗CHF均有效,且疗效相当。     

曲美他嗪与雷米普利对心力衰竭大鼠心肌细胞凋亡及半胱氨酸天冬氨酸蛋白酶3的影响

目的探讨曲美他嗪与雷米普利单用及联合应用对慢性心力衰竭大鼠左心室心肌细胞凋亡情况以及半胱氨酸天冬氨酸蛋白酶3(Caspase-3)表达水平的影响。方法雄性Wistar大鼠50只随机分为假手术组、模型组、曲美他嗪组、雷米普利组和联合用药组(曲美他嗪+雷米普利),每组10只。采用肾上腹主动脉缩窄法制作慢性心力衰竭模型,观察各组左心室舒张末压、左心室压力最大上升及下降速率(±dp/dtmax);TUNEL法检测心肌细胞凋亡指数;SP免疫组织化学法检测各组大鼠左心室心肌Caspase-3水平的表达,RT-PCR测定Caspase-3mRNA水平。结果与模型组比较,曲美他嗪组、雷米普利组和联合用药组左心室舒张末压、心肌凋亡指数明显降低,±dp/dtmax明显升高,差异有统计学意义(P<0.01),Caspase-3蛋白及mRNA表达水平明显降低,差异有统计学意义[(0.14±0.01、0.14±0.02和0.08±0.02)vs(0.22±0.02),(0.54±0.02、0.54±0.02和0.32±0.02)vs(0.91±0.02),P<0.01]。结论曲美他嗪与雷米普利单用及联合应用均可有效改善心功能、抑制心肌细胞凋亡,联合用药的疗效优于单独用药。     

雷米普利抑制心肌梗死大鼠非梗死区心室重构机制探讨

心肌细胞凋亡及间质纤维侣与心肌梗死（MI）后重构密切相关。本实验重点研究梗死后不同阶段非梗死区（NLZ）心肌间质胶原及细胞凋亡的变化情况及应用雷米普利干预的结果。     

Cardiac protection of new compounds from scientific Chinese medicine (SCM)

Objective Purification and Standardization of Chinese herbal extracts became a hot topic since last decade.Though traditional Chinese medicine(TCM)has been used as a mixture from several herbs for centuries,it has been drawn much attention for studying the standardized Chinese herbs using modern technology.Methods Recently,we compared purified Salvia miltiorrhiza extract(PSME)with angiotensin-converting enzyme inhibitor,Ramipril,in in vitro experiments and also in vivo using animal model of myocardial infarction.Results PSME was found to have a significantly higher trolox equivalent antioxidant capacity which indicated a great capacity for scavenging free radicals.PSME could also prevent pyrogallo red bleaching and DNA damage.After 2 weeks treatment with PSME or Ramipril,survival rates of rats with experimental myocardial infarction were marginally increased(68.2% and 71.4%)compared with saline(61.5%).In another recent study,we evaluated the cardioprotective effects of PSME on myocardial ischemia/reperfusion injury in isolated rat hearts and in hypoxic vascular smooth muscle cells.We found that PSME treated hearts showed significant postischemic contractile function recovery(develop pressure recovered to 44.2±4.9% versus 17.1±5.7%,P<0.05;maximum contraction recovered to 57.2±5.9% versus 15.1±6.3%,P<0.001;maximum relaxation restored to 69.3±7.3% versus 15.4±6.3%,P<0.001 in PSME and control group respectively).Conclusions Significant elevated in end-diastolic pressure,which indicated LV stiffening in PSME hearts might be resulted by exceed dose of PSME used.Purified and standardized Chinese herb could provide an alternative regimen for the prevention of ischemic heart disease.     

Cost-effectiveness of the treatment of heart failure with ramipril: a Spanish analysis of the AIRE study

AIMS: To estimate the cost-effectiveness of adding ramipril to conventional treatment in patients with heart failure after myocardial infarction from the perspective of the Spanish National Health System. METHODS AND RESULTS: A retrospective analysis of the AIRE study was made, using previously published data from the clinical trial combined with local Spanish resource and cost data. A typical rehospitalisation for a heart failure episode would last an average of 11.6 days with an average cost of 350.80 per day. The incremental cost of ramipril per life-year gained in the baseline case was 1550.10 after 3.8 years of follow-up. Sensitivity analysis showed that the basic conclusions were robust in spite of extreme variations in the values of the key parameters of the model. CONCLUSION: The use of ramipril in addition to conventional treatment in heart failure patients after myocardial infarction is cost-effective both according to currently accepted international standards of what constitutes a cost-effective intervention and also indirectly by comparing the results with similar pharmaceutical products financed under the Spanish National Health System.     

雷米普利预适应对大鼠心脏延迟性的保护作用

目的探讨雷米普利预适应对大鼠离体心脏缺血-再灌注损伤的延迟性保护作用及机制。方法离体大鼠心脏采用Langendoff灌流法建立心肌缺血再灌注损伤模型。35只大鼠随机分为5组：（1）对照组；（2）缺血-再灌组（I／R组）；（3）雷米普利预处理组（Ramipril 0．05mg／kg）；（4）雷米普利预处理组（Ramipril 0．1mg／kg）：（5）HOE140＋雷米普利预处理组（HOE1400．1mg／kg＋Ramipril 0．1mg／kg）。每组7只。记录左室内压（LVP）、左室内压最大上升速率（＋dp／dtmax）、左室舒张末压（LVEDP）、心率（HR），定时收集冠脉流出液测量冠脉流量（CF）和肌酸激酶（CK）活性。再灌注结束后采用分光光度法测定心肌组织中丙二醛（MDA）含量。结果（1）与对照组比较，I／R组缺血-再灌注后10、20、30min可显著降低LVP和＋dp／dt max（P〈0.01），升高LVEDP（P〈0．01），降低CF（P〈0．01），缺血-再灌注后10、20min显著降低HR（P〈0．01）；（2）与I／R组比较，Ramipril 0．05mg／kg组缺血-再灌注后20、30min可显著升高LVP（P〈0．01）及增加CF（P〈0．05）；缺血-再灌注后10、20、30min可显著升高＋dp／dtmax（P〈0.01），降低LVEDP（P〈0.01）；（3）与I／R组比较，Ramipril 0．1mg／kg组缺血-再灌注后10、20、30min可显著升高LVP（P〈0．01），升高＋dp／dtmax（P〈0.01），降低LVEDP（P〈0.01）；增加CF（P〈0.05）；（4）与Ramipril 0．1mg／kg组比较，HOE1400．1mg／kg＋Ramipril 0．1mg／kg组缺血-再灌注后10、20、30min可显著降低LVP（P〈0.05）；降低＋dp／dtmax（P〈0．05）；升高LVEDP（P〈0.05）；降低CF（P〈0．05）；（5）I／R组缺血-再灌注后10、20、30minCK与对照组比较，均有显著性差异（P均〈0.01）；Ramipril 0．05mg／kg组及Ramipril 0．1mg／kg组缺血-再灌注后10、20、30minCK与I／R组比较，均有显著性差异（P均〈0.01）；HOE1400．1mg／kg＋Ramipril 0．1mg／kg组缺血-再灌注后10、20、30minCK与Ramipril 0．05mg／kg组及Ramipril 0．1mg／kg组比较，均有显著性差异（P均〈0.01）；（6）实验前24h舌下静脉注射雷米普利0．05mg／kg或0．1mg／kg均可显著降低缺血-再灌注心肌组织中MDA含量。结论雷米普利对缺血再灌注诱导离体大鼠心肌损伤具有延迟性保护作用，其机制可能是与激活缓激肽B2受体，减少缓激肽降解有关。     

雷米普利胶囊人体生物等效性研究

 目的评价国产雷米普利胶囊与已上市的雷米普利片的人体生物等效性。方法18名男性健康志愿者随机交叉po雷米普利受试制剂和参比制剂各10 mg,采用液相色谱-质谱法同时测定雷米普利及其活性代谢物雷米普利拉的药物浓度。结果参比制剂及受试制剂的雷米普利的t_max分别为(0.53±0.14)和(0.58±0.17)h,ρmax分别为(42.34±13.37)和(43.84±13.65)μg·L^-1,AUC_0-72分别为(41.70±13.62)和(42.57±11.54)μg·h·L^-1,t_1/2(ke)分别为(2.55±1.55)和(2.40±0.85)h,雷米普利拉的t_max分别为(2.44±0.62)和(2.50±0.51)h,ρ_max分别为(43.28±13.83)和(39.75±13.73)μg·L^-1,AUC_0-72分别为(311.34±99.34)和(312.34±97.74)μg·h·L^-1,t_1/2(ke)分别为(18.80±6.82)和(17.99±5.94)h,国产雷米普利胶囊相对生物利用度以雷米普利计为(104.44±13.07)%,以雷米普利拉计为(101.62±14.56)%。结论方差分析和双单侧t检验结果表明,两种制剂生物等效。     

雷米普利治疗慢性充血性心衰的临床观察

目的:比较雷米普利、地高辛、利尿剂合用与地高辛、利尿剂合用对慢性充血性心力衰竭(CHF)患者心功能、左室射血分数(LVEF)、左室舒张末期内径(LVED)的影响。方法:110例CHF患者随机分为两组,分别接受雷米普利、地高辛、利尿剂(雷米普利组)及地高辛加利尿剂(对照组),治疗3个月。结果:雷米普利组心功能明显改善,LVED由(6 8.2±4.3)mm减少到(60.1±3.3)mm,LVEF由34.7%±8.9%增加到43.4%±9%,治疗前后比较,P均<0.01,对照组心功能明显改善,但LVED、LVEF无明显变化。结论:雷米普利组治疗CHF患者,对降低LVED、提高LVEF疗效较好。     

Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade

Aims/hypothesis. Changes in podocyte number and morphology have been implicated in the pathogenesis of proteinuria and the progression of human and experimental kidney disease. This study sought to examine podocyte foot process and slit pore architecture in experimental diabetic nephropathy and to determine whether such changes were modified with renoprotective intervention by blockade of the renin-angiotensin system. Methods. The number of filtration slits per 100 μm of glomerular basement membrane was assessed by transmission electron microscopy and quantitated histomorphometrically in control animals and in rats with 24 weeks of streptozotocin-induced diabetes. Diabetic rats were either untreated or received the angiotensin converting enzyme inhibitor ramipril, or the angiotensin II type 1 receptor antagonist, valsartan. Results. When compared with control animals, diabetes was associated with a decrease in the number of slit pores per unit length of glomerular basement membrane, indicative of podocyte foot process broadening. Both ramipril and valsartan attenuated these ultrastructural changes to a similar degree. These differences remained after correcting for glomerular volume as a possible confounding variable. Conclusion/interpretation. Preservation of podocyte architecture could contribute to the renoprotective effects of renin-angiotensin system blockade in diabetic nephropathy. [Diabetologia (2001) 44: 878–882] Received: 19 January 2001 and in revised form: 28 March 2001     

雷米普利与BQ-123对大鼠在体心肌缺血/再灌注氧化损伤的保护作用

目的研究雷米普利与BQ-123单用及合用对大鼠在体心肌缺血/再灌注损伤的影响,并从氧化-抗氧化角度初步探讨其机制。方法健康♂Wistar大鼠随机分为假手术(Sham)、缺血/再灌注(I/R)、雷米普利(RAM)、BQ-123(BQ)及联合给药(R&B)共5组。除Sham组,其余均行I/R过程。I/R前24h,RAM及R&B组按1mg.kg-1剂量以雷米普利生理盐水溶液灌胃,其余组均以等剂量生理盐水(NS)灌胃;I/R过程中,BQ及R&B组按10μg.kg-1.min-1,于缺血前10min至缺血30min末用注射泵恒速左侧股静脉输入BQ-123生理盐水溶液2ml,其余组均以等剂量NS持续静脉输入。观察动物心率、血压、心电图ST-段变化,记录缺血期室性心律失常(VA);TTC染色检测心肌梗死情况;比色法检测心肌组织中总-超氧化物歧化酶(T-SOD)、锰-超氧化物歧化酶(Mn-SOD)、过氧化氢酶(CAT)活力及丙二醛(MDA)含量。结果与I/R组比较,各给药组ST-段抬高幅度均明显降低、缺血期VA出现时间明显推迟且持续时间明显缩短、心律失常发生率均明显下降、梗死面积明显缩小、心肌组织T-SOD、Mn-SOD及CAT活力均明显升高、MDA含量明显下降。与单用药组比较,联合给药组在VA出现及持续时间、梗死面积、T-SOD和Mn-SOD活力及MDA含量方面变化更为明显。结论雷米普利、BQ-123单用及联合应用均对大鼠在体心肌缺血/再灌注损伤有保护作用,且两药合用在推迟缺血期VA的出现时间,缩短其持续时间,缩小心肌梗死面积,提高心肌组织SOD活力,降低MDA含量方面优于两药各自单用。