心衰Ⅰ号配方颗粒剂治疗心衰的临床和实验研究
|
摘要
背景
慢性心力衰竭(Chronic Heart Failure,CHF简称心衰)是由于各种器质性或功能性心脏疾病使心室充盈或射血能力受损的一种综合征。我国心衰住院率占同期心血管病的20%,死亡率却占40%,提示预后严重,因此心力衰竭的治疗的是临床重要课题。
传统的强心、扩血管、利尿三联用药在改善患者近期临床情况的同时,却不能降低其死亡,甚至反有可能增加死亡的危险性。究其原因,可能激活了神经内分泌系统,包括交感神经系统(SNS)及肾素-血管紧张素-醛固酮系统(RAAS),未能阻断甚至还可能加速了心肌重构的进程。以血管紧张素转换酶抑制剂(ACEI)为基石的心衰现代治疗方案,通过降低SNS活性,抑制RAAS激活,从而阻断了心肌重构的进展,改善了心功能。传统中医根据心衰时既有心肾阳虚,又有水饮内停和血脉瘀阻的病机特点,拟定了温阳利水,活血化瘀的心衰治疗大法,对于一些中、重症心衰的患者,往往确也能取得良好近期疗效,但是并没有证据表明能摆脱心衰患者的死亡率居高不下的困扰。中医理论认为,物质属阴,功能属阳。在心肌重构的进程中,心肌细胞的凋亡、减少,就是属阴的物质丢失,而属于阴虚,日久则阴损及阳,进而使阳的功能减退:此外,心肌细胞的变性、凋亡、肥大和间质增生,中医则认为是痰、瘀、水气等邪内停的结果。根据以上理论,结合长期临床实践,李七一教授研制出具有益气养阴、活血利水、化痰软坚作用的心衰Ⅰ号配方颗粒剂(简称心衰Ⅰ号),经临床实践证明疗效较好,为进一步深入认识,进行了如下临床试验和动物实验以验证其疗效,探究其作用机理。
研究目的
一、研究心衰Ⅰ号对慢性心力衰竭患者(简称心衰患者)临床症状、6分钟步行试验及血浆脑钠肽水平的影响。
二、研究心衰Ⅰ号改善慢性心力衰竭大鼠(简称心衰大鼠)的血流动力学指标、以及对肾素—血管紧张素—醛固酮系统、心房钠尿肽、内皮素等相关指标的影响,并探讨其机制。
研究内容与方法
一、临床研究部分
1、方法
将51例心衰患者随机分为治疗组26例与对照组25例,两组基础治疗参照中华医学会心血管分会关于《慢性收缩性心力衰竭治疗建议》的标准治疗,治疗组口服心衰Ⅰ号,每日1袋,分2次服。对照组口服心衰Ⅰ号安慰剂,每日1袋,分2次服。4周为1个疗程,观察时间为6个疗程。比较两组治疗后症状体征、生活质量评分、脑钠肽、纽约心功能分级、6分钟步行试验的变化和综合疗效。
2、结果
两组治疗后在症状体征、脑钠肽、6分钟步行试验及综合疗效方面有显著差异。
3、结论
心衰Ⅰ号对心衰患者具有显著改善临床症状,提高临床疗效,改善血浆脑钠肽水平,改善6分钟步行试验的作用,提示该法对心衰患者长期疗效较好。
二、动物试验部分
1、造模及分组方法:
按Fletcher法,对SD(Sprague Dawley)大鼠行左冠状动脉主干结扎术,假手术组开胸后,不结扎冠状动脉。室内饲养,规律照明,自由进食及饮水,饲养4周。按随机数字表法将造模成功后大鼠随机分为4组,每组15只,另设置正常大鼠15只作为空白对照组及15只的假手术组,共计6组。造模成功后开始实验。具体分组情况为:
正常对照组(Con):正常不造模型大鼠,每日灌蒸馏水3ml连续4周。
假手术组(Sha):每日灌蒸馏水3ml,连续4周。
模型组(CHF):确定造模成功后,每日灌蒸馏水3ml,连续4周。
卡托普利组(Cap):确定造模成功后,每日灌卡托普利0.016g/Kg,连续4周。
心衰Ⅰ号小剂量组(XS1):确定造模成功后,每日灌中药颗粒12g生药/kg,连续4周。
心衰Ⅰ号大剂量组(XS2):确定造模成功后,每日灌中药颗粒36 g生药/kg,连续4周。
观察各组动物治疗过程中外观、运动、食欲及水肿、紫绀等症状表现。每日称饲料及水的消耗量。每周称大鼠的体重。给药4周后,对每只大鼠眼眶静脉取血4ml用于放免测定,后进行心功能血流动力学监测。随即将每只大鼠解剖,取完整心脏,生理盐水冲洗后放入液氮罐,保存待测。
2、实验方法
对实验心衰大鼠进行以下实验并记录结果:血流动力学测定、心肺重量的测定、血浆肾素活性(PRA)测定、血浆血管紧张素Ⅱ(AngⅡ)测定、血浆醛固酮(ALD)测定、血浆心房钠尿肽(ANP)测定、血浆内皮素(ET)测定、对抗苯肾上腺素收缩心衰大鼠离体肠系膜上动脉血管作用测定及心肌纤维化程度的检测。
3、研究结果
(1)心衰Ⅰ号对心衰大鼠血流动力学的影响
与模型组比较,心衰Ⅰ号大剂量组与卡托普利组均能增加心衰大鼠的LVSP、+dp/dtmax(P＜0.01),显著降低LVEDP(P＜0.05～0.01),且心衰Ⅰ号大剂量组与卡托普利组相比无明显差异(P＞0.05)。心衰Ⅰ号大剂量组与卡托普利组均能使t～dp/dt max下降(P＜0.05～0.01),似心衰Ⅰ号大剂量组作用更强(P＜0.05)。心衰Ⅰ号小剂量组心衰大鼠的LVSP明显提高(P＜0.05),t～dp/dt max显著下降(P＜0.01)。同时卡托普利组、心衰颗粒大、小剂量组心衰大鼠的SAP均有明显升高(P＜0.05～0.01),似以心衰Ⅰ号大剂量组作用最强。
(2)心衰Ⅰ号对心衰大鼠心、肺的影响
与模型组比较,心衰Ⅰ号大剂量组与卡托普利组均能增加心衰大鼠左室重量和LV/BW(P＜0.05～0.01),且以心衰Ⅰ号大剂量组为显著(P＜0.05)。心衰Ⅰ号小剂量组和卡托普利组均能抑制右室肥厚(P＜0.01),且心衰Ⅰ号小剂量组同时能降低肺脏指数(P＜0.05)。
(3)心衰Ⅰ号对心衰大鼠肾素—血管紧张素—醛固酮系统、心房钠尿肽、内皮素的影响
心衰大鼠RAAS被激活,与正常组比较,血浆PRA、AngⅡ、ALD水平显著提高(P＜0.01)。各给药组治疗后,PRA、AngⅡ、ALD水平明显下降(P＜0.01),其中以心衰Ⅰ号大剂量组下降最为显著。
心衰大鼠血浆ANP水平降低,用心衰Ⅰ号与卡托普利治疗后,ANP有所回升,但无统计学意义。心衰大鼠血浆ET水平显著升高(P＜0.01),各给药组治疗后,血浆ET水平平均有下降(P＜0.05～0.01),其中以心衰Ⅰ号大剂量组最为明显。
(4)心衰Ⅰ号对抗苯肾上腺素收缩心衰大鼠离体肠系膜上动脉血管作用
心衰大鼠肠系膜上动脉血管对苯肾上腺素的反应性增强(P＜0.05),而心衰Ⅰ号与卡托普利均具有明显对抗苯肾上腺素收缩离心体大鼠肠系膜上动脉血管的作用(P＜0.01)。
(5)对心衰大鼠心肌纤维化程度的检测结果
心衰Ⅰ号大小剂量组及卡托普利组心肌间质纤维化程度均小于模型组,卡托普利组心肌间质纤维化程度小于模型组,大于高剂量组。
4、结论
心衰Ⅰ号可以明显改善慢性心力衰竭大鼠的血流动力学指标、对肾素—血管紧张素—醛固酮系统、心房钠尿肽、内皮素等相关指标均有不同程度改善,其中以大剂量组更为显著。此外,心衰Ⅰ号可以降低心衰大鼠心肌纤维化的程度。
Background
Chronic Heart Failure(Chronic Heart Failure,CHF referred to as heart failure ) is a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventride to fill with or eject blood.In China,the heart failure hospitalization rates over accounted for 20%of the same period cardiovascular disease,the mortality rate accounted for 40%,suggesting a serious prognosis.Therefore the treatment of heart failure is a clinical important issue.
Traditional cardiac,vasodilative,diuretic drugs may be activated neuroendocrine system, failed to block the process of myocardial remodeling,and even likely to accelerate the process of myocardial remodeling,so in the near future to improve the clinical condition of patients at the same time,but should not reduce their death,or even anti-are likely to increase the risk of death.By angiotensin-converting enzyme inhibitor(ACEI) as the cornerstone of modern treatment of heart failure by reducing sympathetic nervous system(SNS) activity,inhibiting the renin - angiotensin - aldosterone system(RAAS) activation,which has impacted off the progress of cardiac remodeling and improve cardiac function results.Traditional Chinese medicine in accordance with the heart failure pathogenesis characteristics,not only the deficiency of heart-Yang and kidney-Yang but also retention of fluid within the body and blood Stagnation,developed Onyang diuresis,huoxuehuayu Dafa treatment of heart failure, for some,the severe heart failure patients can often do a good short-term efficacy.However, there is no long-term treatment in patients with heart failure out of the troubled high mortality rate.Chinese medicine theory holds that material belong to Yin,Yang is function.In the process of cardiac remodeling,myocardial apoptosis,the material reduced Yin lost in the first place,and ultimately Yin impairment involve Yang,,so that the function rreduced Yang dysfunction..Normal decrease in the number of myocardial cells,reflects the Yin impairment, while the remaining myocardial cells hypertrophy,Chinese medicine consider that it is phlegm,stagnant blood,such as fluid vapor suspended in the outcome of evil.Cardiac myocyte apoptosis and cardiac myocyte hypertrophy,myocardial structure and function is the main reason for change.Based on the above theory with long-term clinical practice,Professor Li Qiyi developed XinShuai Formula granulesⅠ(referred to as XinShuaiⅠ) through the overall conditioning,multi-target,multi-link acting on the neuroendocrine system,as well as neurohumoral factors,inhibition ventricular remodeling and the role of anti-heart failure. Research purposes
First,to study XinShuaiⅠin patients with chronic heart failure(referred to as heart failure rats) on clinical symptoms,6-minute walk test and plasma brain natriuretic peptide levels.
Second,to study XinShuaiⅠin rats with chronic heart failure(referred to as heart failure rats) to improve hemodynamic parameters,as well as the renin - angiotensin - aldosterone system, atrial natriuretic peptide,endothelin and other related indicators,and explore its mechanism, so as to clinical application XinShuaiⅠto provide experimental basis,better services for the vast number of patients with heart failure.
Research contents and methods
First,.the part of clinical research
1,methods
51 cases of heart failure patients will be randomly divided into treatment group 26 cases and 25 cases of the control group,two groups with reference to basic treatment of the Chinese Medical Association of Cardiovascular Branch regarding "Chronic systolic heart failure treatment recommendations," the standard treatment,The treatment group oral XinShuaiⅠ1 bag per day,at 2 times service,the control group oral placebo 1 bag per day,at 2 times service.4 weeks for a course of treatment,observation time of 6 treatments.Compared between the two groups after treatment signs and symptoms,quality of life score,brain natriuretic peptide,New York cardiac function grade,6 minute walking test and general effect.
2,result
The two groups after treatment at signs and symptoms,brain natriuretic peptide,6-minute walk test and general efficacy has significant differences.
3,conclusion
XinShuaiⅠin patients with heart failure significantly improved clinical symptoms,improve clinical efficacy,improvement in plasma brain natriuretic peptide levels,6 minute walking test to improve the role,suggesting XinShuaiⅠhas better long-term efficacy.in patients with heart failure.
Second,the part of animal experiments
1.model and group methods:
By Fletcher,act of SD rats with left main coronary artery ligation,sham-operated group, after thoracotomy,non-coronary artery ligation.Indoor farming,the law of the lighting,free eating and drinking water,rearing four weeks.Random number table,after the successful model rats were randomly divided into 4 groups,each 15,and the other set of normal rats 15 as blank control group and 15 of the sham-operated group,for a total of 6 groups.After the success of the beginning of model experiments.Specific sub-cases as follows:
Normal control group(Con):do not build a normal rat model,daily irrigation 3ml distilled water for 4 weeks.
Sham-operated group(Sha):distilled water daily irrigation 3ml,for 4 weeks.
Model group(CHF):determined after modeling success,the daily irrigation of distilled water 3ml,for 4 weeks.
Captopril group(Cap):determined after modeling success,the daily irrigation captopril 0.016g/Kg,for 4 weeks.
XinShuaiⅠof low-dose group(XS1):determined after modeling success,the daily irrigation of XinShuaiⅠ12g crude drug / kg,for 4 weeks.
XinShuaiⅠof high-dose group(XS2):determined after modeling success,the daily irrigation of XinShuaiⅠ36g crude drug / kg,for 4 weeks.
Observation of animals in each group during the treatment appearance,movement,loss of appetite,and edema,cyanosis and other symptoms.Said daily feed and water consumption. Week that the body weight of rats.After 4 weeks,administration of each rat orbital venous blood 4ml for RIAand then proceed the determination of cardiac function and hemodynamic monitoring.To each rat was dissected,check integrity of the heart,after washing with normal saline add liquid nitrogen cans,preserved under test.
2.experimental methods
Experimental rats and recorded the following experimental results:determination of hemodynamic and cardiopulmonary weight,determination of plasma renin activity(PRA), plasma angiotensinⅡ(AngⅡ),plasma aldosterone(ALD),A-type natriuretic peptide(ANP) and plasma endothelin(ET).Against the role of contraction of heart failure rats superior mesenteric artery by phenylephrine and detection of the extent of myocardial fibrosis.
3.results
(1) XinShuaiⅠon heart failure rats hemodynamics
Compared with model group,XinShuaiⅠof high-dose group and captopril group can increase heart failure in rats LVSP,dp / dt max(P＜0.01),significantly decreased LVEDP(P＜0.05～0.01),and XinShuaiⅠof high-dose group and the captopril group compared with no significant difference(P＞0.05).XinShuaiⅠof high-dose group and captopril group can t～dp / dt max decreased(P＜0.05～0.01),XinShuaiⅠmay granules stronger role in high-dose group(P＜0.05).XinShuaiⅠof low-dose group of heart failure in rats with heart failure LVSP significantly improve(P＜0.05),t～dp / dt max decreased significantly(P＜0.01).At the same time,the captopril group,XinShuaiⅠhigh and low dose groups of heart failure in rats with SAP were significantly higher(P＜0.05～0.01),XinShuaiⅠseems to particles of high-dose group of the strongest role.
(2) XinShuaiⅠon heart failure rats in heart,lung impact
Compared with model group,XinShuaiⅠof high-dose group and captopril group are able to increase left ventricular weight and LV / BW(P＜0.05～0.01),and XinShuaiⅠ high-dose group was significantly(P＜0.05).XinShuaiⅠof low-dose group and captopril group are able to inhibit the right ventricular hypertrophy(P＜0.01),XinShuaiⅠof low-dose group of particles at the same time can reduce the lung index(P＜0.05).
(3) XinShuaiⅠon heart failure rats in renin - angiotensin - aldosterone system,atrial natriuretic peptide,endothelin
RAAS is activated in rats with heart failure,compared with the normal group,PRA,AngⅡ,ALD levels was significantly enhance(P＜0.01).Of drug-treated group after treatment, PRA,AngⅡ,ALD levels were significantly decreased(P＜0.01),of which XinShuaiⅠof high-dose group of heart failure the most significant decline.
The levels of plasma ANP in Heart failure rats,after treatment of XinShuaiⅠand captopril,the levels of ANP has been picked up,but without statistical significance.Heart failure rats plasma ET levels significantly increased(P＜0.01),after treatment of drug-treated group,plasma ET levels have declined on average(P＜0.05～0.01),of which XinShuaiⅠof high-dose group is most obvious.
(4) XinShuaiⅠagainst the contraction of heart failure rats superior mesenteric artery by phenylephrine
Heart failure rats superior mesenteric artery response to phenylephrine increased(P＜0.05), and XinShuaiⅠand captopril groups are clearly against the hcontraction of heart failure rats superior mesenteric artery by phenylephrine(P＜0.01).
(5) Detection of the extent of myocardial fibrosis in heart failure rats The extent of myocardial fibrosis in XinShuaiⅠof high and low dose groups and the captopril group were all less than model group,the extent of myocardial fibrosis in the captopril group is less than the model group,higher than high-dose group.
4.conclusion
XinShuaiⅠcan improve hemodynamic parameters significantly in heart failure rats,improve in varying degrees on renin - angiotensin - aldosterone system,atrial natriuretic peptide, endothelin and other related indicators,of the total,the high-dose group is more as significant. In addition,XinShuaiⅠcan can reduce the extent of myocardial fibrosis
慢性心力衰竭(Chronic Heart Failure,CHF简称心衰)是由于各种器质性或功能性心脏疾病使心室充盈或射血能力受损的一种综合征。我国心衰住院率占同期心血管病的20%,死亡率却占40%,提示预后严重,因此心力衰竭的治疗的是临床重要课题。
传统的强心、扩血管、利尿三联用药在改善患者近期临床情况的同时,却不能降低其死亡,甚至反有可能增加死亡的危险性。究其原因,可能激活了神经内分泌系统,包括交感神经系统(SNS)及肾素-血管紧张素-醛固酮系统(RAAS),未能阻断甚至还可能加速了心肌重构的进程。以血管紧张素转换酶抑制剂(ACEI)为基石的心衰现代治疗方案,通过降低SNS活性,抑制RAAS激活,从而阻断了心肌重构的进展,改善了心功能。传统中医根据心衰时既有心肾阳虚,又有水饮内停和血脉瘀阻的病机特点,拟定了温阳利水,活血化瘀的心衰治疗大法,对于一些中、重症心衰的患者,往往确也能取得良好近期疗效,但是并没有证据表明能摆脱心衰患者的死亡率居高不下的困扰。中医理论认为,物质属阴,功能属阳。在心肌重构的进程中,心肌细胞的凋亡、减少,就是属阴的物质丢失,而属于阴虚,日久则阴损及阳,进而使阳的功能减退:此外,心肌细胞的变性、凋亡、肥大和间质增生,中医则认为是痰、瘀、水气等邪内停的结果。根据以上理论,结合长期临床实践,李七一教授研制出具有益气养阴、活血利水、化痰软坚作用的心衰Ⅰ号配方颗粒剂(简称心衰Ⅰ号),经临床实践证明疗效较好,为进一步深入认识,进行了如下临床试验和动物实验以验证其疗效,探究其作用机理。
研究目的
一、研究心衰Ⅰ号对慢性心力衰竭患者(简称心衰患者)临床症状、6分钟步行试验及血浆脑钠肽水平的影响。
二、研究心衰Ⅰ号改善慢性心力衰竭大鼠(简称心衰大鼠)的血流动力学指标、以及对肾素—血管紧张素—醛固酮系统、心房钠尿肽、内皮素等相关指标的影响,并探讨其机制。
研究内容与方法
一、临床研究部分
1、方法
将51例心衰患者随机分为治疗组26例与对照组25例,两组基础治疗参照中华医学会心血管分会关于《慢性收缩性心力衰竭治疗建议》的标准治疗,治疗组口服心衰Ⅰ号,每日1袋,分2次服。对照组口服心衰Ⅰ号安慰剂,每日1袋,分2次服。4周为1个疗程,观察时间为6个疗程。比较两组治疗后症状体征、生活质量评分、脑钠肽、纽约心功能分级、6分钟步行试验的变化和综合疗效。
2、结果
两组治疗后在症状体征、脑钠肽、6分钟步行试验及综合疗效方面有显著差异。
3、结论
心衰Ⅰ号对心衰患者具有显著改善临床症状,提高临床疗效,改善血浆脑钠肽水平,改善6分钟步行试验的作用,提示该法对心衰患者长期疗效较好。
二、动物试验部分
1、造模及分组方法:
按Fletcher法,对SD(Sprague Dawley)大鼠行左冠状动脉主干结扎术,假手术组开胸后,不结扎冠状动脉。室内饲养,规律照明,自由进食及饮水,饲养4周。按随机数字表法将造模成功后大鼠随机分为4组,每组15只,另设置正常大鼠15只作为空白对照组及15只的假手术组,共计6组。造模成功后开始实验。具体分组情况为:
正常对照组(Con):正常不造模型大鼠,每日灌蒸馏水3ml连续4周。
假手术组(Sha):每日灌蒸馏水3ml,连续4周。
模型组(CHF):确定造模成功后,每日灌蒸馏水3ml,连续4周。
卡托普利组(Cap):确定造模成功后,每日灌卡托普利0.016g/Kg,连续4周。
心衰Ⅰ号小剂量组(XS1):确定造模成功后,每日灌中药颗粒12g生药/kg,连续4周。
心衰Ⅰ号大剂量组(XS2):确定造模成功后,每日灌中药颗粒36 g生药/kg,连续4周。
观察各组动物治疗过程中外观、运动、食欲及水肿、紫绀等症状表现。每日称饲料及水的消耗量。每周称大鼠的体重。给药4周后,对每只大鼠眼眶静脉取血4ml用于放免测定,后进行心功能血流动力学监测。随即将每只大鼠解剖,取完整心脏,生理盐水冲洗后放入液氮罐,保存待测。
2、实验方法
对实验心衰大鼠进行以下实验并记录结果:血流动力学测定、心肺重量的测定、血浆肾素活性(PRA)测定、血浆血管紧张素Ⅱ(AngⅡ)测定、血浆醛固酮(ALD)测定、血浆心房钠尿肽(ANP)测定、血浆内皮素(ET)测定、对抗苯肾上腺素收缩心衰大鼠离体肠系膜上动脉血管作用测定及心肌纤维化程度的检测。
3、研究结果
(1)心衰Ⅰ号对心衰大鼠血流动力学的影响
与模型组比较,心衰Ⅰ号大剂量组与卡托普利组均能增加心衰大鼠的LVSP、+dp/dtmax(P＜0.01),显著降低LVEDP(P＜0.05～0.01),且心衰Ⅰ号大剂量组与卡托普利组相比无明显差异(P＞0.05)。心衰Ⅰ号大剂量组与卡托普利组均能使t～dp/dt max下降(P＜0.05～0.01),似心衰Ⅰ号大剂量组作用更强(P＜0.05)。心衰Ⅰ号小剂量组心衰大鼠的LVSP明显提高(P＜0.05),t～dp/dt max显著下降(P＜0.01)。同时卡托普利组、心衰颗粒大、小剂量组心衰大鼠的SAP均有明显升高(P＜0.05～0.01),似以心衰Ⅰ号大剂量组作用最强。
(2)心衰Ⅰ号对心衰大鼠心、肺的影响
与模型组比较,心衰Ⅰ号大剂量组与卡托普利组均能增加心衰大鼠左室重量和LV/BW(P＜0.05～0.01),且以心衰Ⅰ号大剂量组为显著(P＜0.05)。心衰Ⅰ号小剂量组和卡托普利组均能抑制右室肥厚(P＜0.01),且心衰Ⅰ号小剂量组同时能降低肺脏指数(P＜0.05)。
(3)心衰Ⅰ号对心衰大鼠肾素—血管紧张素—醛固酮系统、心房钠尿肽、内皮素的影响
心衰大鼠RAAS被激活,与正常组比较,血浆PRA、AngⅡ、ALD水平显著提高(P＜0.01)。各给药组治疗后,PRA、AngⅡ、ALD水平明显下降(P＜0.01),其中以心衰Ⅰ号大剂量组下降最为显著。
心衰大鼠血浆ANP水平降低,用心衰Ⅰ号与卡托普利治疗后,ANP有所回升,但无统计学意义。心衰大鼠血浆ET水平显著升高(P＜0.01),各给药组治疗后,血浆ET水平平均有下降(P＜0.05～0.01),其中以心衰Ⅰ号大剂量组最为明显。
(4)心衰Ⅰ号对抗苯肾上腺素收缩心衰大鼠离体肠系膜上动脉血管作用
心衰大鼠肠系膜上动脉血管对苯肾上腺素的反应性增强(P＜0.05),而心衰Ⅰ号与卡托普利均具有明显对抗苯肾上腺素收缩离心体大鼠肠系膜上动脉血管的作用(P＜0.01)。
(5)对心衰大鼠心肌纤维化程度的检测结果
心衰Ⅰ号大小剂量组及卡托普利组心肌间质纤维化程度均小于模型组,卡托普利组心肌间质纤维化程度小于模型组,大于高剂量组。
4、结论
心衰Ⅰ号可以明显改善慢性心力衰竭大鼠的血流动力学指标、对肾素—血管紧张素—醛固酮系统、心房钠尿肽、内皮素等相关指标均有不同程度改善,其中以大剂量组更为显著。此外,心衰Ⅰ号可以降低心衰大鼠心肌纤维化的程度。
Background
Chronic Heart Failure(Chronic Heart Failure,CHF referred to as heart failure ) is a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventride to fill with or eject blood.In China,the heart failure hospitalization rates over accounted for 20%of the same period cardiovascular disease,the mortality rate accounted for 40%,suggesting a serious prognosis.Therefore the treatment of heart failure is a clinical important issue.
Traditional cardiac,vasodilative,diuretic drugs may be activated neuroendocrine system, failed to block the process of myocardial remodeling,and even likely to accelerate the process of myocardial remodeling,so in the near future to improve the clinical condition of patients at the same time,but should not reduce their death,or even anti-are likely to increase the risk of death.By angiotensin-converting enzyme inhibitor(ACEI) as the cornerstone of modern treatment of heart failure by reducing sympathetic nervous system(SNS) activity,inhibiting the renin - angiotensin - aldosterone system(RAAS) activation,which has impacted off the progress of cardiac remodeling and improve cardiac function results.Traditional Chinese medicine in accordance with the heart failure pathogenesis characteristics,not only the deficiency of heart-Yang and kidney-Yang but also retention of fluid within the body and blood Stagnation,developed Onyang diuresis,huoxuehuayu Dafa treatment of heart failure, for some,the severe heart failure patients can often do a good short-term efficacy.However, there is no long-term treatment in patients with heart failure out of the troubled high mortality rate.Chinese medicine theory holds that material belong to Yin,Yang is function.In the process of cardiac remodeling,myocardial apoptosis,the material reduced Yin lost in the first place,and ultimately Yin impairment involve Yang,,so that the function rreduced Yang dysfunction..Normal decrease in the number of myocardial cells,reflects the Yin impairment, while the remaining myocardial cells hypertrophy,Chinese medicine consider that it is phlegm,stagnant blood,such as fluid vapor suspended in the outcome of evil.Cardiac myocyte apoptosis and cardiac myocyte hypertrophy,myocardial structure and function is the main reason for change.Based on the above theory with long-term clinical practice,Professor Li Qiyi developed XinShuai Formula granulesⅠ(referred to as XinShuaiⅠ) through the overall conditioning,multi-target,multi-link acting on the neuroendocrine system,as well as neurohumoral factors,inhibition ventricular remodeling and the role of anti-heart failure. Research purposes
First,to study XinShuaiⅠin patients with chronic heart failure(referred to as heart failure rats) on clinical symptoms,6-minute walk test and plasma brain natriuretic peptide levels.
Second,to study XinShuaiⅠin rats with chronic heart failure(referred to as heart failure rats) to improve hemodynamic parameters,as well as the renin - angiotensin - aldosterone system, atrial natriuretic peptide,endothelin and other related indicators,and explore its mechanism, so as to clinical application XinShuaiⅠto provide experimental basis,better services for the vast number of patients with heart failure.
Research contents and methods
First,.the part of clinical research
1,methods
51 cases of heart failure patients will be randomly divided into treatment group 26 cases and 25 cases of the control group,two groups with reference to basic treatment of the Chinese Medical Association of Cardiovascular Branch regarding "Chronic systolic heart failure treatment recommendations," the standard treatment,The treatment group oral XinShuaiⅠ1 bag per day,at 2 times service,the control group oral placebo 1 bag per day,at 2 times service.4 weeks for a course of treatment,observation time of 6 treatments.Compared between the two groups after treatment signs and symptoms,quality of life score,brain natriuretic peptide,New York cardiac function grade,6 minute walking test and general effect.
2,result
The two groups after treatment at signs and symptoms,brain natriuretic peptide,6-minute walk test and general efficacy has significant differences.
3,conclusion
XinShuaiⅠin patients with heart failure significantly improved clinical symptoms,improve clinical efficacy,improvement in plasma brain natriuretic peptide levels,6 minute walking test to improve the role,suggesting XinShuaiⅠhas better long-term efficacy.in patients with heart failure.
Second,the part of animal experiments
1.model and group methods:
By Fletcher,act of SD rats with left main coronary artery ligation,sham-operated group, after thoracotomy,non-coronary artery ligation.Indoor farming,the law of the lighting,free eating and drinking water,rearing four weeks.Random number table,after the successful model rats were randomly divided into 4 groups,each 15,and the other set of normal rats 15 as blank control group and 15 of the sham-operated group,for a total of 6 groups.After the success of the beginning of model experiments.Specific sub-cases as follows:
Normal control group(Con):do not build a normal rat model,daily irrigation 3ml distilled water for 4 weeks.
Sham-operated group(Sha):distilled water daily irrigation 3ml,for 4 weeks.
Model group(CHF):determined after modeling success,the daily irrigation of distilled water 3ml,for 4 weeks.
Captopril group(Cap):determined after modeling success,the daily irrigation captopril 0.016g/Kg,for 4 weeks.
XinShuaiⅠof low-dose group(XS1):determined after modeling success,the daily irrigation of XinShuaiⅠ12g crude drug / kg,for 4 weeks.
XinShuaiⅠof high-dose group(XS2):determined after modeling success,the daily irrigation of XinShuaiⅠ36g crude drug / kg,for 4 weeks.
Observation of animals in each group during the treatment appearance,movement,loss of appetite,and edema,cyanosis and other symptoms.Said daily feed and water consumption. Week that the body weight of rats.After 4 weeks,administration of each rat orbital venous blood 4ml for RIAand then proceed the determination of cardiac function and hemodynamic monitoring.To each rat was dissected,check integrity of the heart,after washing with normal saline add liquid nitrogen cans,preserved under test.
2.experimental methods
Experimental rats and recorded the following experimental results:determination of hemodynamic and cardiopulmonary weight,determination of plasma renin activity(PRA), plasma angiotensinⅡ(AngⅡ),plasma aldosterone(ALD),A-type natriuretic peptide(ANP) and plasma endothelin(ET).Against the role of contraction of heart failure rats superior mesenteric artery by phenylephrine and detection of the extent of myocardial fibrosis.
3.results
(1) XinShuaiⅠon heart failure rats hemodynamics
Compared with model group,XinShuaiⅠof high-dose group and captopril group can increase heart failure in rats LVSP,dp / dt max(P＜0.01),significantly decreased LVEDP(P＜0.05～0.01),and XinShuaiⅠof high-dose group and the captopril group compared with no significant difference(P＞0.05).XinShuaiⅠof high-dose group and captopril group can t～dp / dt max decreased(P＜0.05～0.01),XinShuaiⅠmay granules stronger role in high-dose group(P＜0.05).XinShuaiⅠof low-dose group of heart failure in rats with heart failure LVSP significantly improve(P＜0.05),t～dp / dt max decreased significantly(P＜0.01).At the same time,the captopril group,XinShuaiⅠhigh and low dose groups of heart failure in rats with SAP were significantly higher(P＜0.05～0.01),XinShuaiⅠseems to particles of high-dose group of the strongest role.
(2) XinShuaiⅠon heart failure rats in heart,lung impact
Compared with model group,XinShuaiⅠof high-dose group and captopril group are able to increase left ventricular weight and LV / BW(P＜0.05～0.01),and XinShuaiⅠ high-dose group was significantly(P＜0.05).XinShuaiⅠof low-dose group and captopril group are able to inhibit the right ventricular hypertrophy(P＜0.01),XinShuaiⅠof low-dose group of particles at the same time can reduce the lung index(P＜0.05).
(3) XinShuaiⅠon heart failure rats in renin - angiotensin - aldosterone system,atrial natriuretic peptide,endothelin
RAAS is activated in rats with heart failure,compared with the normal group,PRA,AngⅡ,ALD levels was significantly enhance(P＜0.01).Of drug-treated group after treatment, PRA,AngⅡ,ALD levels were significantly decreased(P＜0.01),of which XinShuaiⅠof high-dose group of heart failure the most significant decline.
The levels of plasma ANP in Heart failure rats,after treatment of XinShuaiⅠand captopril,the levels of ANP has been picked up,but without statistical significance.Heart failure rats plasma ET levels significantly increased(P＜0.01),after treatment of drug-treated group,plasma ET levels have declined on average(P＜0.05～0.01),of which XinShuaiⅠof high-dose group is most obvious.
(4) XinShuaiⅠagainst the contraction of heart failure rats superior mesenteric artery by phenylephrine
Heart failure rats superior mesenteric artery response to phenylephrine increased(P＜0.05), and XinShuaiⅠand captopril groups are clearly against the hcontraction of heart failure rats superior mesenteric artery by phenylephrine(P＜0.01).
(5) Detection of the extent of myocardial fibrosis in heart failure rats The extent of myocardial fibrosis in XinShuaiⅠof high and low dose groups and the captopril group were all less than model group,the extent of myocardial fibrosis in the captopril group is less than the model group,higher than high-dose group.
4.conclusion
XinShuaiⅠcan improve hemodynamic parameters significantly in heart failure rats,improve in varying degrees on renin - angiotensin - aldosterone system,atrial natriuretic peptide, endothelin and other related indicators,of the total,the high-dose group is more as significant. In addition,XinShuaiⅠcan can reduce the extent of myocardial fibrosis
引文
[1]周仲英、金妙文、吴勉华.益阴助阳、活血通脉法治疗充血性心力衰竭的临床研究[J].南京中医药大学学报,2000,11(1):13.
[2]尹克春、吴焕林.邓铁涛治疗心力衰竭经验介绍[J].江苏中医药 2002,23(7):9-10
[3]吴勉华.充血性心力衰竭中医病机探讨[J].南京中医药大学学报(自然科学版)2001,17(4):206-209
[4]姜淑琴.心力衰竭的中医辨治[J].现代中西医结合杂志 2004,13(13):1799
[5]曹雪滨等.充血性心力衰竭的中医辨证分型特点[J].甘肃中医学院学报,1999;16(3):13
[6]郭毅.试论心衰及其治疗体会[J].四川中医,1996;14(8):6
[7]谭璐芸 安莉萍.谈郭维琴教授辨治心衰经验[J].新疆中医药 2000,18(4):51-52
[8]曹贵民.中医对心力衰竭的认识和治疗[J].陕西中医学院学报,1997;20(3):6
[9]梁东辉,杨俊.充血性心力衰竭的辨证分析及中西医结合治疗规律初探[J].实用中西医结合杂志,1997,10(11):1069
[10]葛鸿庆,赵梁,郝李敏.邓铁涛教授从脾论治慢性充血性心力衰竭之经验[J].上海中医药杂志2002,36(4):9-10
[11]谭璐芸 郭维琴治疗心力衰竭经验介绍[J].云南中医学院学报 2000,23(2):43-44
[12]丁爱国.韩子江辨治充血性心衰的思路和方法[J].辽宁中医杂志 1998,25(5):199
[13]朱波.李七一心衰辨治心法[J].江苏中医药 2008,40(12):18-19
[14]张元.浅谈“心衰”的临证辨治[J].湖南中医药导报 2004,10(6):24-25
[15]王素琴.心衰的中医辨证施治[J].河北医学 2002,8(3):283-284
[16]杨培君、杨磊.充血性心力衰竭的中医证治概要[J].陕西中医学院学报 2002,25(1)2-5
[17]车向前.辨证治疗心力衰竭体会[J].天津中医,2000,17(1):47-48
[19]杨蕊琳.病、证结合论治充血性心力衰竭[J].贵阳中医学院学报,2000,22(4):36
[20]冯国标.略论慢性心衰的辨证论治[J].河南中医药学刊,1998,13(2):6
[21]黄永生.心衰论治[J].湖南中医药导报,2000,6(9):3-5
[22]顾炳岐.救心方治疗慢性心力衰竭34例[J].中医药研究,1999,15(2):56
[23]谢乐.中医分型治疗充血性心力衰竭77例[J].四川中医,2002,20(6):41
[24]刘建民,张忠祥,闰振界.中医辨证治疗慢性心力衰竭182例临床观察[J].国医论坛,2002,17(3):20-21
[25]谭焕民,骆亚利.辨证分型治疗慢性充血性心力衰竭86例.河南中医,1999,19(3):40}41
[26]李治淮.充血性心力衰竭[M].北京:科学技术文献出版社,1991:432-441
[27]王敏生.温阳强心汤治疗慢性心衰30例[J].实用中医内科杂志 2005,19(6):557
[28]朱波.中西结合治疗充血性心力衰竭临床研究[J].中医药研究 2001,17(3)8-9
[29]白民刚,刘玉华.康心力胶囊治疗充血性心力衰竭临床与实验研究[J].中医杂志,2001,42(3):156-158.
[30]唐剑林 益气活血利水法配西药治疗充血性心力衰竭48例[J].陕西中医 2005,26(11):1135-1136
[31]郑军温 阳利水法治疗慢性心力衰竭48例[J].陕西中医 2005,26(2):102-103
[32]胡元会,曹雪滨,曹贵民.中药心复康治疗气虚血疲型充血性心力衰竭33例疗效观察[J].浙江中医学院学报,2002,24(2):39
[33]马波.中医治疗肺心病合并心衰52例[J].陕西中医,1994,15(10):443
[34]金玫、黄丽娟、王振裕、易京红、王倩心衰合剂对慢性心力衰竭的干预[J].北京中医杂志 2003,22(3):10-12
[35]黄衍寿,冼绍祥,丁有钦,等.保心康治疗气阳虚型充血性心力衰竭的临床研究[J].中药新药与临床药理,2000,11(5):261-265.
[36]李秋凤,高雅,张俊明.强心乐治疗慢性充血性心力衰竭的临床研究[J].中医研究,1998,11(3):11
[37]邓德明,顾充,苏维广,等.心宁煎剂治疗充血性心力衰竭50例[J].1临床研究.中医杂志,2002,43(8):593-594
[38]陶泉,金朝霞.益气活血利水法治疗心力衰竭123例[J].四川中医,2001,19(11):37
[39]金妙文,方泰惠,周仲英,等.从阴阳两型心脉淤滞证辨治充血性心力衰竭的研究[J].中国中西医结合急救杂志,2002,9(5):258-262.
[40和]李念珊,雷敏,郭延秋,等.生脉散加味与卡托普利治疗慢性心衰疗效比较[J].临床军医杂志,2000,28(2):17
[41]曹航,程丑夫.附子强心胶囊治疗充血性心力衰竭30例总结[J].湖南中医杂志,2002,18(4):4-5.
[42]金长娟.强心泻肺方治疗难治性心衰30例[J].中医杂志,1997,(11):661
[43]喻正科,黄江波.参茂颗粒治疗慢性充血性心力衰竭98例总结[J].湖南中医杂志,2001,17(6):8
[44]王双乾.心衰饮治疗心力衰竭32例[J].陕西中医,2002,23(6):506
[45]周智林,俞娉,林玎等.黄芪注射液治疗充血性心力衰竭的疗效研究.中国中西医结合杂志,2001,21(10):747-749
[46]何作友,李树勤,李秀华等.生脉液对慢性充血性心力衰竭的急性血流动力学作用的超声心动图研究[J].四川中医,1993,11(5):11
[47]田俊.参附注射液对充血性心力衰竭病人血液流变学的影响及疗效观察[J].中西医结合心脑血管病杂志,2003,1(6):324-326,
[48]刘毅.参附注射液治疗慢性充血性心力衰竭40例I临床观察[J].中国中医急症,2008,17(1):51-52
[49]李红,张宇.参麦注射液治疗充血性心力衰竭37例[J].天津中医,2002,19(3):69.
[50]艾俊,田浪.黄芪注射液与丹参注射液联合治疗慢性肺心病心衰[J].现代中西医结合杂志,2001,10(6):525-528.
[51]徐济明,解玉水.黄杨宁治疗心功能不全的初步观察[J].上海中医药杂志,1993,(3):14-16
[52]吴时达,吴桐,吴昌碧,等.温阳健心灵口服液治疗收缩功能不全性心力衰竭的临床研究[[J].中国中西医结合急救杂志,2001,8(2):88
[53]夏军.强心栓治疗充血性心力衰竭的临床观察与药理研究[J].中西医结合杂志,1984,4(2):97
[54]安海英,黄丽娟,金敬善,等.益气温阳和活血利水对充血性心力衰竭患者神经内分泌系统的影响[J].中国中西医结合杂志,2002,22(5):349-352.
[55]刘金民,沈承玲,赵海滨.健心汤对充血性心力衰竭患者血清细胞因子的干预作用[J].中国中医急症,2004,13(1):5-6.
[56]李庆海,吕安清,张芳,等.参麦注射液对充血性心力衰竭患者心率变异性的影响[J].中国中西医结合急救杂志,2000,7(5):273-275.
[57]李荣堂,胡建福.复方丹参滴丸对冠心病合并充血性心力衰竭患者血浆CGRP和ET浓度的影响[J].中国老年学杂志,2003,23(7):424-425.
[58]洪永敦,冼绍祥,陈宇鹏,等.益气温阳活血利水中药对充血性心力衰竭患者内皮素及一氧化氮的影响[J].中药新药与临床药理,2000,11(2):71-73.
[59]刘洪智,高传玉,雷健等.实验性心力衰竭大鼠模型的建立及评价[J].中国老年学杂志,2007,27(18):1760-1763
[60]王振涛,李敏,赵明镜,等.活血、益气注射液对心梗后左心衰大鼠心肌局部对AngⅡ影响的对比实验研究[J].中国中医药信息杂志,2000,7(8):35-36
[61]蔡辉,胡婉英,董耀荣,等.充血性心力衰竭大鼠心肌组织和血浆血管紧张素Ⅱ的改变及鹿角方的作用[J].安徽中医临床杂志,1999,11(3):165-166
[62]杜丽,熊曼琪,梅国强,等.加味真武汤对充血性心力衰竭少阴病阴虚水停证兔心肌细胞凋亡的影响[J].中国医药学报,2000,15(2):26}29
[63]王显,朱明军,孙建芝,等.心衰康对电镜下CHF模型心肌线粒体的影响[J].上海中医药大学学报,2000.14(1):33-35.
[64]肖春香,何泽云,曾松吟,等.泻水扶正剂对实验性兔心力衰竭心钠素、环磷酸腺苷及环磷酸鸟苷的影响[[J].湖南中医学院学报,1998,18(1):56
[65]王保和,孙兰军,赵英强,等.强心冲剂对慢性心力衰竭大鼠内皮素的影响[J].中国中医药信息杂志,2003.10(11):29-30.
[66]罗心平,施海胆,曾治宇,等.黄芪对大鼠心肌梗塞在左室功能及胶原改变的影响[J].中国病理生理杂志,1999,15(7):639
[67]徐伟建,张道亮,李颖,等。保心合剂对心衰大鼠血清AngⅡ及IL-6的影响[J]。中国中医急症,2006,15(10):74 98
[68]Sharon Ann Hunt,William T.Abraham,Arthur M.Feldman,et al.ACC/AHA 2005 Guideline Update for the Diagnosis and Managementof Chronic Heart Failure in the Adult[J].Circulation.2005;112:e154-e235.
[69]Collucci WS.Molecular and cellular mechanisms of myocardial failure[J].Am J Cardiol,1997,80:15L- 25L.
[70]Sabbath H,Shrove VG.Apoptosis in heartfailure.Prog[J].Cardiovasc Dis,1998,40:549- 562.
[71] Verkerk AO, Veldkamp MW, BaartscheerA,etal.Ionicmechanism of delayed after depolarizations in ventricular cells isolated from human end stage failing hearts[J] .Circulation,2001,104 (22) :2728-2733.
[72] Watanbe T, Yamaki M, Yamauchi S, et al.Regional prolongation of ARI and altered restitution properties cause ventricular arrhythmia in heart failure [J]. Am J Physiol,2002,282 (1) :218.
[73] Han W, Chartier D, Li D, et al.Ionic remodeling of cardiac purkinje cells by congestive heart failure [J] .Circulation,2001,104 (17) :2095-2100.
[74]van Bilsen M, Smeets PJ, Gilde AL et al.Metabolic remodeling of the failing heart:the cardiac burn-out syndrome ? Cardio vasc Res, 2004, 61: 218-26
[75]Geltman EM, Smith JL, Beecher D, et aLAltered regional myocardial metabolism in congestive cardiomyopathy detected by position tomography [J] .Am J Med, 1983, 74: 773-785
[76]Scheubel RJ, Tostlebe M, Simm A, et aLDysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression[J].AM Coll Cardiol,2002,40:21 74-81
[77] Weiss RG, Gerstenblith G, Bottomley PA.ATP flux through creatine kinase in the normal, stressed, and failing human heart[J] .Proc Natl Acad Sci USA, 2005, 102: 808-813
[78] Dipla K, Mattiello JA, Margulies K, et al.The sarcoplasmic reticulum and Na~+ Ca~(2+) exchanger both contribute to the Ca~(2+) transient of failing human ventricular myocytes[J] .Circ Res,1999,84:435-444.
[79]. Packer M, Cohn JN, Abraham WT, et al. Consensus recommendations for the management of chronic heart failure. Am J Cardiol enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study. Lancet 2003;361:1843-8.
[80]. Swartz SL, Williams GH, Hollenberg NK, Levine L, Dluhy RG, Moore TJ. Captopril-induced changes in prostaglandin production: relationship to vascular responses in normal man. J Clin Invest 1980;65:1257-64.
[81]. Brown NJ, Ryder D, Gainer JV, Morrow JD, Nadeau J. Differential effects of angiotensin converting enzyme inhibitors on the vasodepressor and prostacyclin responses to bradykinin. J Pharmacol Exp Ther 1996;279:703-12.
[82]. Gainer JV, Morrow JD, Loveland A, King DJ, Brown NJ. Effect of bradykinin-receptor blockade on the response to angiotensinconverting- enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med 1998;339:1285-92.
[83]. Linz W, Scholkens BA. A specific B2-bradykinin receptor antagonist HOE 140 abolishes the antihypertrophic effect of ramipril. Br J Pharmacol 1992;105:771-2.
[84]. McDonald KM, Garr M, Carlyle PF, et al. Relative effects of alpha 1-adrenoceptor blockade, converting enzyme inhibitor therapy, and angiotensin II subtype 1 receptor blockade on ventricular remodeling in the dog. Circulation 1994;90:3034-46.
[85]. McDonald KM, Mock J, D'Aloia A, et al. Bradykinin antagonism inhibits the antigrowth effect of converting enzyme inhibition in the dog myocardium after discrete transmural myocardial necrosis. Circulation 1995;91:2043-8.
[86]. Bastien NR, Juneau AV, Ouellette J, Lambert C. Chronic ATI receptor blockade and angiotensin-converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathic hamsters: effects on cardiac hypertrophy and survival. Cardiovasc Res 1999;43:77-85.
[87]. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991;325:303-10.
[88]. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan comparedwith captopril on mortality in patients with symptomatic heart failure: randomised trial: the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582-7.
[89]. Packer M, Medina N, Yushak M, Meller J. Hemodynamic patterns of response during long-term captopril therapy for severe chronic heart failure. Circulation 1983;68:803-12.
[90]. Captopril Multicenter Research Group. A placebo-controlled trial1999;83:1A-38A.
[91]. Pflugfelder PW, Baird MG, Tonkon MJ, DiBianco R, Pitt B, for the Quinapril Heart Failure Trial Investigators. Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. J Am Coll Cardiol 1993;22:1557-63.
[92]. Packer M, Lee WH, Medina N, Yushak M, Kessler PD. Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure. Ann Intern Med 1987;106: 346-54.
[93]. Cody RJ, Covit AB, Schaer GL, Laragh JH, Sealey JE, Feldschuh J. Sodium and water balance in chronic congestive heart failure. J Clin Invest 1986;77:1441-52.
[94]. Struthers AD. Angiotensin II receptor antagonists for heart failure. Heart 1998;80:5-6. Editorial.
[95]. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomized trial. Lancet 1999;353:9-13.
[96]. Hjalmarson A, Goldstein S, Fagerberg B, et al, for the MERIT-HF Study Group. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). JAMA 2000;283:1295-302.
[97]. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651-8.
[98]. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 2001;357:1385-90.
[99]. Colucci WS, Packer M, Bristow MR, et al, for the US Carvedilol Heart Failure Study Group. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. Circulation1996; 94:2800-6.
[100]. Massie B, Kramer B, Haughom F. Postural hypotension and tachycardia during hydralazine- isosorbide dinitrate therapy for chronic heart failure. Circulation 1981;63:658-64.
[101]. Waagstein F, Caidahl K, Wallentin I, Bergh CH, Hjalmarson A. Long-term beta-blockade in dilated cardiomyopathy: effects of short- and long-term metoprolol treatment followed by withdrawaland readministration of metoprolol. Circulation 1989;80:551-63.
[102]A Zevedoe R, Newtong E, Parker JD. Cardiac and systemic sympathetic activity in response to clonidine in human heart failure[J]. Am Coll Cardiol, 1999, 33: 186-191
[103]Coats AJ.Heart Failure 99:the MOXCON story.Int J Cardiol,1999,71:109-lll
[104]. Wilson JR, Reichek N, Dunkman WB, Goldberg S. Effect of diuresis on the performance of the failing left ventricle in man.Am J Med 1981;70:234-9.
[105]. Parker JO, for the Ibopamine Study Group. The effects of oral ibopamine in patients with mild heart failure: a double blind placebo controlled comparison to furosemide. Int J Cardiol 1993;40:221-7.
[106]. Richardson A, Bayliss J, Scriven AJ, Parameshwar J, Poole- Wilson PA, Sutton GC. Double-blind comparison of captopril alone against frusemide plus amiloride in mild heart failure. Lancet 1987;2:709-ll.
[107]. Akera T, Baskin SI, Tobin T, Brody TM. Ouabain: temporal relationship between the inotropic effect and the in vitro binding to,and dissociation from, (Na + + K + )-activated ATPase. Naunynlarizations and triggered activity during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Circulation 1991;84:1732-40.
[108]. Gheorghiade M, Ferguson D. Digoxin: a neurohormonal modulator in heart failure? Circulation 1991;84:2181-6.
[109]. Gheorghiade M, Adams KF Jr, Colucci WS. Digoxin in the management of cardiovascular disorders. Circulation 2004; 109:2959-64.
[110]. Rahimtoola SH. Digitalis therapy for patients in clinical heart failure. Circulation 2004; 109:2942-6.
[111]. Uretsky BF, Jessup M, Konstam MA, et al, for the Enoximone Multicenter Trial Group. Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure: lack of benefit compared with placebo. Circulation 1990; 82:774-80.
[112]. Cohn JN, Goldstein SO, Greenberg BH, et al, for the Vesnarinone Trial Investigators. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. N Engl J Med 1998;339:1810-6.
[113]. Cowley AJ, Skene AM, for the Enoximone Investigators. Treatment of severe heart failure: quantity or quality of life? Atrialof enoximone. BHeart J 1994;72:226-30.
[114]. Feldman AM, Bristow MR, Parmley WW, et al, for the Vesnarinone Study Group. Effects of vesnarinone on morbidity and mortality in patients with heart failure. N Engl J Med 1993; 329:149-55.
[115]. Hampton JR, van Veldhuisen DJ, Kleber FX, et al. Randomised study of effect of ibopamine on survival in patients with advancedsevere heart failure: Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators. Lancet 1997;349:971-7.
[116]. Lubsen J, Just H, Hjalmarsson AC, et al. Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial. Heart 1996; 76: 223-31.
[117]. Packer M, Carver JR, Rodeheffer RJ, et al, for the PROMISE Study Research Group. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468-75.
[118]. Elkayam U, Johnson JV, Shotan A, et al. Double-blind, placebocontrolled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition. Circulation 1999;99:2652-7.
[119]. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8- bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989;83:1774-7.
[120]. Calderone A, Thaik CM, Takahashi N, Chang DLF, Colucci WS. Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts. J Clin Invest 1998;101:812-8.
[121]. Jugdutt BI, Khan MI. Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction. Circulation 1994;89:2297-307.
[122]M aack C, Kartest, Kilter H, et al.Oxygen free radical release in human failing myocardium is associated with increased activity of racl-GTpase and represent sat ar get for statin treatment[J]. Circulation, 2003, 108: 1567-1574
[123]Ray JC, Gong Y, Sykora K, et al.Statin use and survival outcomes in elderly patients with heart failure.Arch intern Med, 2005, 165: 62-67
[124]Mozafarian D, Nye R, Levy WC.Statin therapy is associated with lower mortality among patients with server heart failure.Am[J]. Cardiol, 2004, 93: 1124-1129
[125]. Colucci WS, Elkayam U, Horton DP, et al, for the Nesiritide Study Group. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. N Engl J Med 2000; 343:246-53.
[126]. Elkayam U, Akhter MW, Singh H, Khan S, Usman A. Comparison of effects on left ventricular filling pressure of intravenous nesiritide and high-dose nitroglycerin in patients with decompensated heart failure. Am J Cardiol 2004;93:237-40.
[127]. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 2002;287:1531-40.
[128]. Goldsmith SR. Congestive heart failure: potential role of arginine vasopressin antagonists in the therapy of heart failure. Congest Heart Fail 2002;8:251-6.
[129]. Gheorghiade M, Niazi I, Ouyang J, et al. Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation 2003;107:2690-6.
[130]. Udelson JE, Smith WB, Hendrix GH, et al. Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation 2001; 104: 2417-23.
[131]. Gheorghiade M, Gattis WA, O'Connor CM, et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 2004;291:1963-71.
[132]. Russell SD, Selaru P, Pyne DA, et al. Rationale for use of an exercise end point and design for the ADVANCE (A Dose evaluation of a Vasopressin ANtagonist in CHF patients undergoing Exercise) trial. Am Heart J 2003;145:179-86.
[133]. Silverman ME, Pressel MD, Brackett JC, Lauria SS, Gold MR, Gottlieb SS. Prognostic value of the signal-averaged electrocardiogram and a prolonged QRS in ischemic and nonischemic cardiomyopathy. Am J Cardiol 1995;75:460-4.
[134]. Wilensky RL, Yudelman P, Cohen AI, et al. Serial electrocardiographic changes in idiopathic dilated cardiomyopathy confirmed at necropsy. Am J Cardiol 1988;62:276-83.
[135]. Grines CL, Bashore TM, Boudoulas H, Olson S, Shafer P, Wooley CF. Functional abnormalities in isolated left bundle branch block: the effect of interventricular asynchrony. Circulation 1989;79:845-53.
[136]. Xiao HB, Lee CH, Gibson DG. Effect of left bundle branch block on diastolic function in dilated cardiomyopathy. Br Heart J 1991;66:443-7.
[137]. Takeshita A, Basta LL, Kioschos JM. Effect of intermittent left bundle branch block on left ventricular performance. Am J Med 1974;56:251-5.
[138]. Xiao HB, Roy C, Fujimoto S, Gibson DG. Natural history of abnormal conduction and its relation to prognosis in patients with dilated cardiomyopathy. Int J Cardiol 1996;53:163-70.
[139]. Shamim W, Francis DP, Yousufuddin M, et al. Intraventricular conduction delay: a prognostic marker in chronic heart failure. Int J Cardiol 1999;70:171-8.
[140]. Unverferth DV, Magorien RD, Moeschberger ML, Baker PB, Fetters JK, Leier CV. Factors influencing the one-year mortality of dilated cardiomyopathy. Am J Cardiol 1984;54:147-52.
[141]. Blanc JJ, Etienne Y, Gilard M, et al. Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study. Circulation 1997;96:3273-7.
[142]. Kass DA, Chen CH, Curry C, et al. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 1999;99:1567-73.
[143].Toussaint JF,Lavergne T,Ollitraut J,et al.Biventricular pacing in severe heart failure patients reverses electromechanical dyssynchronization from apex to base.Pacing Clin Electrophysiol 2000;23:1731-4.
[144].Nelson GS,Berger RD,Fetics BJ,et al.Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundlebranch block.Circulation 2000;102:3053-9.
[145]Kaab S,Barth AS,Margerie D,etal.Global gene expression in human myocardium ol imgo nucleotide microarray analysis of regional diversity and transcriptional regulation in heart failure[J]。JMOLMed,2004,82(5):308-316
[146]Cowie MR,Mosterd A,Wood DA,et al.The epidemiology of heart failure.Eur Heart J,1999,18:208-225.
[147]John Cleland,Hull(UK),Henry Dargie,Glasgow(UK),Helmut Drexler,Hannover(Germany) etal.Guidelines for the diagnosis and treatment of chronic heart failure:executive summary(update 2005).European Heart Journal(2005)26,1115-1140
[148]中华医学会心血管病分会 中华心血管病杂志编辑委员会·慢性心力衰竭诊断治疗指南·中华心血管病杂志,2007,35(12):1076-1096
[149]Fletcher PJ,Pfeffer JM,Pfeffer MA.Left ventricular diastolic pressvolume relations in rats with healed myocardial infarction[J].Circulation Research,1981,49(3):618-627.
[150]McMurray JJ,Ray SG,Abdullah I et al.Plasma endothelin in chronic heart failure[J].Circulation 1992;85(4):1347-1379
[151]陈筱潮,徐明彤。心血管系统内分泌学[M].广州:中山大学出版社,2007.96-98,136-137
[152]McGregor DD·The effects of sympathetic nerve stimulation vasoconstrictor response in perfused mesenteric blood vessele of the rats·Physiology 1965;177:21.
[153]方泰惠·石斛对大鼠肠系膜的动脉血管的作用[J]·南京中医学院学报1991;7(2):100-101.
[154]孟伟栋,汪爱虎,孙宝贵。醛固酮及其拮抗剂在心力衰竭中的研究进展。国外医学心血管疾病分册2002;29(3);145-147
[155]Tokola H,Hautala V,Marttila M,et al.Mechanicall oad- induced alterations in B-type natriuretic peptide gene expression[J].Can J Physiol Parmaco,2001,79(8):646- 653.
[156]Ito T,Yoshimura M,Nakamura S,et ai.Inhibitory effect of natriuretic peptides on aidosterone synthase gene expression in cultured neonatal ratcardiocytes.Circulation,2003,107(6):807-810.
[157]Maisel A.B-type natriuretic peptid elevels:diagnostic and therapeutic potential.Cardiovasc Toxcol,2001,1(2):159-164.
[158]Kruger S,Graf J,Merx M,et al.Brain natriuretic peptide predicts right heart failure in patients with acute pulmonary embolism.Am Heart J,2004,147:60- 65.
[159]Leroyg,Uzanl,Bugugnanimj,et al.The value of repeated determination of brain natriuretic peptide for the diagnosis of unstable angina[J].Arch mal Coeur Vaiss,2003,96(4):305- 310.
[160]GuyattGH,SullivanMJ,ThompsonPJ,etal.The 6-minutewalk:anew measure of exercise capa city inpatients with chronic heart failure[J].CanMedAssocJ,1985,132:919-923.
[161]LipkinDP,ScrivenAJ,CrakeT,etal.Six-minute walking test for assessing exercise capa city in chronic heart failure[J].BrMedJ,1986,292:653-655.
[162]BittnerV,WeinerDH,YusufS,etal.Prediction of mortality and morbidity with a 6-minute walk test inpatients with left ventriculardy sfunction[J].JAMA,1993,270(14):1702-1707.
[163]侯云生,何国祥,何振山,等·黄芪对试验性急性心肌梗塞后心室重构的影响[J].现代中西医结合杂志,1999,8(12):1940-1941
[164]侯云生,何国祥,何振山,等·黄芪对急性心肌梗死后左室重构的治疗作用[J].心脏杂志,2000,12(4):270-272
[165]刘艳霞,刘在萍,焦建杰,等.黄芪苷Ⅳ对正常和心功能受抑制大鼠左心室心肌力学的影响[J].中草药,2001,32(4):332-334.
[166]周吉燕,樊懿,孔建龙,等.黄芪中不同提取成分对在体大鼠心肌缺血-再灌注损伤的心功能影响[J].中国中药杂志,2000,25(5):300-302.
[167]彭定风,柯丽,李论,等.黄芪对缺氧心肌细胞的保护作用[J].临床心血管病杂志,2003,19(4):234-236.
[168]何蕾.黄芪注射液抗心肌细胞再灌注损伤的作用及机制[J].世界急危重病医学杂志,2006,3(4):1366.
[169]程金波,卫洪昌,章忱,等.麦冬提取物抗犬心肌缺血的药效学实验研究[J].中国病理生理杂志,2001,17(8):810.
[170]顾双林,纪克.麦冬对实验性心肌梗塞及心肌缺血时亚微结构的影响[J].上海中医药杂志,1993,27(7):44-45.
[171]蒋凤荣,张旭,范俊,等.麦冬药理作用研究进展[J].中医药学刊,2006,24(2):236-237.
[172]范俊,张旭.麦冬对心脑血管系统药理作用研究进展[J].南京中医药大学学报,2006,22(4):270-272.
[173]王丽娟,王勇.麦冬药理作用与临床应用研究进展[J].中华医学研究杂志,2005,5(9):885-887.
[174]周跃华,徐德生,冯怡,等.麦冬提取物对小鼠心肌营养血流量的影响[J].中国实验方剂学杂志,2003,9(1):22-24.
[175]舒晓燕,侯大斌,阮期平.山茱萸的研究进展[J].中国药业,2007,16(10):60-62
[176]杨芳.蒲黄之药理[J]浙江中医学院学报,1998,22(1):49
[177]陈奇,陶子平,毕明等.心益好的药理研究[J].中草药1985;16(9):22
[178]Albertus J S.Medicinal and pharmaceutical uses ofseaweed natural products:A review.Journal of AppliedPhycology,2004,16:245-262.
[2]尹克春、吴焕林.邓铁涛治疗心力衰竭经验介绍[J].江苏中医药 2002,23(7):9-10
[3]吴勉华.充血性心力衰竭中医病机探讨[J].南京中医药大学学报(自然科学版)2001,17(4):206-209
[4]姜淑琴.心力衰竭的中医辨治[J].现代中西医结合杂志 2004,13(13):1799
[5]曹雪滨等.充血性心力衰竭的中医辨证分型特点[J].甘肃中医学院学报,1999;16(3):13
[6]郭毅.试论心衰及其治疗体会[J].四川中医,1996;14(8):6
[7]谭璐芸 安莉萍.谈郭维琴教授辨治心衰经验[J].新疆中医药 2000,18(4):51-52
[8]曹贵民.中医对心力衰竭的认识和治疗[J].陕西中医学院学报,1997;20(3):6
[9]梁东辉,杨俊.充血性心力衰竭的辨证分析及中西医结合治疗规律初探[J].实用中西医结合杂志,1997,10(11):1069
[10]葛鸿庆,赵梁,郝李敏.邓铁涛教授从脾论治慢性充血性心力衰竭之经验[J].上海中医药杂志2002,36(4):9-10
[11]谭璐芸 郭维琴治疗心力衰竭经验介绍[J].云南中医学院学报 2000,23(2):43-44
[12]丁爱国.韩子江辨治充血性心衰的思路和方法[J].辽宁中医杂志 1998,25(5):199
[13]朱波.李七一心衰辨治心法[J].江苏中医药 2008,40(12):18-19
[14]张元.浅谈“心衰”的临证辨治[J].湖南中医药导报 2004,10(6):24-25
[15]王素琴.心衰的中医辨证施治[J].河北医学 2002,8(3):283-284
[16]杨培君、杨磊.充血性心力衰竭的中医证治概要[J].陕西中医学院学报 2002,25(1)2-5
[17]车向前.辨证治疗心力衰竭体会[J].天津中医,2000,17(1):47-48
[19]杨蕊琳.病、证结合论治充血性心力衰竭[J].贵阳中医学院学报,2000,22(4):36
[20]冯国标.略论慢性心衰的辨证论治[J].河南中医药学刊,1998,13(2):6
[21]黄永生.心衰论治[J].湖南中医药导报,2000,6(9):3-5
[22]顾炳岐.救心方治疗慢性心力衰竭34例[J].中医药研究,1999,15(2):56
[23]谢乐.中医分型治疗充血性心力衰竭77例[J].四川中医,2002,20(6):41
[24]刘建民,张忠祥,闰振界.中医辨证治疗慢性心力衰竭182例临床观察[J].国医论坛,2002,17(3):20-21
[25]谭焕民,骆亚利.辨证分型治疗慢性充血性心力衰竭86例.河南中医,1999,19(3):40}41
[26]李治淮.充血性心力衰竭[M].北京:科学技术文献出版社,1991:432-441
[27]王敏生.温阳强心汤治疗慢性心衰30例[J].实用中医内科杂志 2005,19(6):557
[28]朱波.中西结合治疗充血性心力衰竭临床研究[J].中医药研究 2001,17(3)8-9
[29]白民刚,刘玉华.康心力胶囊治疗充血性心力衰竭临床与实验研究[J].中医杂志,2001,42(3):156-158.
[30]唐剑林 益气活血利水法配西药治疗充血性心力衰竭48例[J].陕西中医 2005,26(11):1135-1136
[31]郑军温 阳利水法治疗慢性心力衰竭48例[J].陕西中医 2005,26(2):102-103
[32]胡元会,曹雪滨,曹贵民.中药心复康治疗气虚血疲型充血性心力衰竭33例疗效观察[J].浙江中医学院学报,2002,24(2):39
[33]马波.中医治疗肺心病合并心衰52例[J].陕西中医,1994,15(10):443
[34]金玫、黄丽娟、王振裕、易京红、王倩心衰合剂对慢性心力衰竭的干预[J].北京中医杂志 2003,22(3):10-12
[35]黄衍寿,冼绍祥,丁有钦,等.保心康治疗气阳虚型充血性心力衰竭的临床研究[J].中药新药与临床药理,2000,11(5):261-265.
[36]李秋凤,高雅,张俊明.强心乐治疗慢性充血性心力衰竭的临床研究[J].中医研究,1998,11(3):11
[37]邓德明,顾充,苏维广,等.心宁煎剂治疗充血性心力衰竭50例[J].1临床研究.中医杂志,2002,43(8):593-594
[38]陶泉,金朝霞.益气活血利水法治疗心力衰竭123例[J].四川中医,2001,19(11):37
[39]金妙文,方泰惠,周仲英,等.从阴阳两型心脉淤滞证辨治充血性心力衰竭的研究[J].中国中西医结合急救杂志,2002,9(5):258-262.
[40和]李念珊,雷敏,郭延秋,等.生脉散加味与卡托普利治疗慢性心衰疗效比较[J].临床军医杂志,2000,28(2):17
[41]曹航,程丑夫.附子强心胶囊治疗充血性心力衰竭30例总结[J].湖南中医杂志,2002,18(4):4-5.
[42]金长娟.强心泻肺方治疗难治性心衰30例[J].中医杂志,1997,(11):661
[43]喻正科,黄江波.参茂颗粒治疗慢性充血性心力衰竭98例总结[J].湖南中医杂志,2001,17(6):8
[44]王双乾.心衰饮治疗心力衰竭32例[J].陕西中医,2002,23(6):506
[45]周智林,俞娉,林玎等.黄芪注射液治疗充血性心力衰竭的疗效研究.中国中西医结合杂志,2001,21(10):747-749
[46]何作友,李树勤,李秀华等.生脉液对慢性充血性心力衰竭的急性血流动力学作用的超声心动图研究[J].四川中医,1993,11(5):11
[47]田俊.参附注射液对充血性心力衰竭病人血液流变学的影响及疗效观察[J].中西医结合心脑血管病杂志,2003,1(6):324-326,
[48]刘毅.参附注射液治疗慢性充血性心力衰竭40例I临床观察[J].中国中医急症,2008,17(1):51-52
[49]李红,张宇.参麦注射液治疗充血性心力衰竭37例[J].天津中医,2002,19(3):69.
[50]艾俊,田浪.黄芪注射液与丹参注射液联合治疗慢性肺心病心衰[J].现代中西医结合杂志,2001,10(6):525-528.
[51]徐济明,解玉水.黄杨宁治疗心功能不全的初步观察[J].上海中医药杂志,1993,(3):14-16
[52]吴时达,吴桐,吴昌碧,等.温阳健心灵口服液治疗收缩功能不全性心力衰竭的临床研究[[J].中国中西医结合急救杂志,2001,8(2):88
[53]夏军.强心栓治疗充血性心力衰竭的临床观察与药理研究[J].中西医结合杂志,1984,4(2):97
[54]安海英,黄丽娟,金敬善,等.益气温阳和活血利水对充血性心力衰竭患者神经内分泌系统的影响[J].中国中西医结合杂志,2002,22(5):349-352.
[55]刘金民,沈承玲,赵海滨.健心汤对充血性心力衰竭患者血清细胞因子的干预作用[J].中国中医急症,2004,13(1):5-6.
[56]李庆海,吕安清,张芳,等.参麦注射液对充血性心力衰竭患者心率变异性的影响[J].中国中西医结合急救杂志,2000,7(5):273-275.
[57]李荣堂,胡建福.复方丹参滴丸对冠心病合并充血性心力衰竭患者血浆CGRP和ET浓度的影响[J].中国老年学杂志,2003,23(7):424-425.
[58]洪永敦,冼绍祥,陈宇鹏,等.益气温阳活血利水中药对充血性心力衰竭患者内皮素及一氧化氮的影响[J].中药新药与临床药理,2000,11(2):71-73.
[59]刘洪智,高传玉,雷健等.实验性心力衰竭大鼠模型的建立及评价[J].中国老年学杂志,2007,27(18):1760-1763
[60]王振涛,李敏,赵明镜,等.活血、益气注射液对心梗后左心衰大鼠心肌局部对AngⅡ影响的对比实验研究[J].中国中医药信息杂志,2000,7(8):35-36
[61]蔡辉,胡婉英,董耀荣,等.充血性心力衰竭大鼠心肌组织和血浆血管紧张素Ⅱ的改变及鹿角方的作用[J].安徽中医临床杂志,1999,11(3):165-166
[62]杜丽,熊曼琪,梅国强,等.加味真武汤对充血性心力衰竭少阴病阴虚水停证兔心肌细胞凋亡的影响[J].中国医药学报,2000,15(2):26}29
[63]王显,朱明军,孙建芝,等.心衰康对电镜下CHF模型心肌线粒体的影响[J].上海中医药大学学报,2000.14(1):33-35.
[64]肖春香,何泽云,曾松吟,等.泻水扶正剂对实验性兔心力衰竭心钠素、环磷酸腺苷及环磷酸鸟苷的影响[[J].湖南中医学院学报,1998,18(1):56
[65]王保和,孙兰军,赵英强,等.强心冲剂对慢性心力衰竭大鼠内皮素的影响[J].中国中医药信息杂志,2003.10(11):29-30.
[66]罗心平,施海胆,曾治宇,等.黄芪对大鼠心肌梗塞在左室功能及胶原改变的影响[J].中国病理生理杂志,1999,15(7):639
[67]徐伟建,张道亮,李颖,等。保心合剂对心衰大鼠血清AngⅡ及IL-6的影响[J]。中国中医急症,2006,15(10):74 98
[68]Sharon Ann Hunt,William T.Abraham,Arthur M.Feldman,et al.ACC/AHA 2005 Guideline Update for the Diagnosis and Managementof Chronic Heart Failure in the Adult[J].Circulation.2005;112:e154-e235.
[69]Collucci WS.Molecular and cellular mechanisms of myocardial failure[J].Am J Cardiol,1997,80:15L- 25L.
[70]Sabbath H,Shrove VG.Apoptosis in heartfailure.Prog[J].Cardiovasc Dis,1998,40:549- 562.
[71] Verkerk AO, Veldkamp MW, BaartscheerA,etal.Ionicmechanism of delayed after depolarizations in ventricular cells isolated from human end stage failing hearts[J] .Circulation,2001,104 (22) :2728-2733.
[72] Watanbe T, Yamaki M, Yamauchi S, et al.Regional prolongation of ARI and altered restitution properties cause ventricular arrhythmia in heart failure [J]. Am J Physiol,2002,282 (1) :218.
[73] Han W, Chartier D, Li D, et al.Ionic remodeling of cardiac purkinje cells by congestive heart failure [J] .Circulation,2001,104 (17) :2095-2100.
[74]van Bilsen M, Smeets PJ, Gilde AL et al.Metabolic remodeling of the failing heart:the cardiac burn-out syndrome ? Cardio vasc Res, 2004, 61: 218-26
[75]Geltman EM, Smith JL, Beecher D, et aLAltered regional myocardial metabolism in congestive cardiomyopathy detected by position tomography [J] .Am J Med, 1983, 74: 773-785
[76]Scheubel RJ, Tostlebe M, Simm A, et aLDysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression[J].AM Coll Cardiol,2002,40:21 74-81
[77] Weiss RG, Gerstenblith G, Bottomley PA.ATP flux through creatine kinase in the normal, stressed, and failing human heart[J] .Proc Natl Acad Sci USA, 2005, 102: 808-813
[78] Dipla K, Mattiello JA, Margulies K, et al.The sarcoplasmic reticulum and Na~+ Ca~(2+) exchanger both contribute to the Ca~(2+) transient of failing human ventricular myocytes[J] .Circ Res,1999,84:435-444.
[79]. Packer M, Cohn JN, Abraham WT, et al. Consensus recommendations for the management of chronic heart failure. Am J Cardiol enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study. Lancet 2003;361:1843-8.
[80]. Swartz SL, Williams GH, Hollenberg NK, Levine L, Dluhy RG, Moore TJ. Captopril-induced changes in prostaglandin production: relationship to vascular responses in normal man. J Clin Invest 1980;65:1257-64.
[81]. Brown NJ, Ryder D, Gainer JV, Morrow JD, Nadeau J. Differential effects of angiotensin converting enzyme inhibitors on the vasodepressor and prostacyclin responses to bradykinin. J Pharmacol Exp Ther 1996;279:703-12.
[82]. Gainer JV, Morrow JD, Loveland A, King DJ, Brown NJ. Effect of bradykinin-receptor blockade on the response to angiotensinconverting- enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med 1998;339:1285-92.
[83]. Linz W, Scholkens BA. A specific B2-bradykinin receptor antagonist HOE 140 abolishes the antihypertrophic effect of ramipril. Br J Pharmacol 1992;105:771-2.
[84]. McDonald KM, Garr M, Carlyle PF, et al. Relative effects of alpha 1-adrenoceptor blockade, converting enzyme inhibitor therapy, and angiotensin II subtype 1 receptor blockade on ventricular remodeling in the dog. Circulation 1994;90:3034-46.
[85]. McDonald KM, Mock J, D'Aloia A, et al. Bradykinin antagonism inhibits the antigrowth effect of converting enzyme inhibition in the dog myocardium after discrete transmural myocardial necrosis. Circulation 1995;91:2043-8.
[86]. Bastien NR, Juneau AV, Ouellette J, Lambert C. Chronic ATI receptor blockade and angiotensin-converting enzyme (ACE) inhibition in (CHF 146) cardiomyopathic hamsters: effects on cardiac hypertrophy and survival. Cardiovasc Res 1999;43:77-85.
[87]. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med 1991;325:303-10.
[88]. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan comparedwith captopril on mortality in patients with symptomatic heart failure: randomised trial: the Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582-7.
[89]. Packer M, Medina N, Yushak M, Meller J. Hemodynamic patterns of response during long-term captopril therapy for severe chronic heart failure. Circulation 1983;68:803-12.
[90]. Captopril Multicenter Research Group. A placebo-controlled trial1999;83:1A-38A.
[91]. Pflugfelder PW, Baird MG, Tonkon MJ, DiBianco R, Pitt B, for the Quinapril Heart Failure Trial Investigators. Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. J Am Coll Cardiol 1993;22:1557-63.
[92]. Packer M, Lee WH, Medina N, Yushak M, Kessler PD. Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure. Ann Intern Med 1987;106: 346-54.
[93]. Cody RJ, Covit AB, Schaer GL, Laragh JH, Sealey JE, Feldschuh J. Sodium and water balance in chronic congestive heart failure. J Clin Invest 1986;77:1441-52.
[94]. Struthers AD. Angiotensin II receptor antagonists for heart failure. Heart 1998;80:5-6. Editorial.
[95]. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomized trial. Lancet 1999;353:9-13.
[96]. Hjalmarson A, Goldstein S, Fagerberg B, et al, for the MERIT-HF Study Group. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). JAMA 2000;283:1295-302.
[97]. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651-8.
[98]. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet 2001;357:1385-90.
[99]. Colucci WS, Packer M, Bristow MR, et al, for the US Carvedilol Heart Failure Study Group. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. Circulation1996; 94:2800-6.
[100]. Massie B, Kramer B, Haughom F. Postural hypotension and tachycardia during hydralazine- isosorbide dinitrate therapy for chronic heart failure. Circulation 1981;63:658-64.
[101]. Waagstein F, Caidahl K, Wallentin I, Bergh CH, Hjalmarson A. Long-term beta-blockade in dilated cardiomyopathy: effects of short- and long-term metoprolol treatment followed by withdrawaland readministration of metoprolol. Circulation 1989;80:551-63.
[102]A Zevedoe R, Newtong E, Parker JD. Cardiac and systemic sympathetic activity in response to clonidine in human heart failure[J]. Am Coll Cardiol, 1999, 33: 186-191
[103]Coats AJ.Heart Failure 99:the MOXCON story.Int J Cardiol,1999,71:109-lll
[104]. Wilson JR, Reichek N, Dunkman WB, Goldberg S. Effect of diuresis on the performance of the failing left ventricle in man.Am J Med 1981;70:234-9.
[105]. Parker JO, for the Ibopamine Study Group. The effects of oral ibopamine in patients with mild heart failure: a double blind placebo controlled comparison to furosemide. Int J Cardiol 1993;40:221-7.
[106]. Richardson A, Bayliss J, Scriven AJ, Parameshwar J, Poole- Wilson PA, Sutton GC. Double-blind comparison of captopril alone against frusemide plus amiloride in mild heart failure. Lancet 1987;2:709-ll.
[107]. Akera T, Baskin SI, Tobin T, Brody TM. Ouabain: temporal relationship between the inotropic effect and the in vitro binding to,and dissociation from, (Na + + K + )-activated ATPase. Naunynlarizations and triggered activity during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Circulation 1991;84:1732-40.
[108]. Gheorghiade M, Ferguson D. Digoxin: a neurohormonal modulator in heart failure? Circulation 1991;84:2181-6.
[109]. Gheorghiade M, Adams KF Jr, Colucci WS. Digoxin in the management of cardiovascular disorders. Circulation 2004; 109:2959-64.
[110]. Rahimtoola SH. Digitalis therapy for patients in clinical heart failure. Circulation 2004; 109:2942-6.
[111]. Uretsky BF, Jessup M, Konstam MA, et al, for the Enoximone Multicenter Trial Group. Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure: lack of benefit compared with placebo. Circulation 1990; 82:774-80.
[112]. Cohn JN, Goldstein SO, Greenberg BH, et al, for the Vesnarinone Trial Investigators. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. N Engl J Med 1998;339:1810-6.
[113]. Cowley AJ, Skene AM, for the Enoximone Investigators. Treatment of severe heart failure: quantity or quality of life? Atrialof enoximone. BHeart J 1994;72:226-30.
[114]. Feldman AM, Bristow MR, Parmley WW, et al, for the Vesnarinone Study Group. Effects of vesnarinone on morbidity and mortality in patients with heart failure. N Engl J Med 1993; 329:149-55.
[115]. Hampton JR, van Veldhuisen DJ, Kleber FX, et al. Randomised study of effect of ibopamine on survival in patients with advancedsevere heart failure: Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators. Lancet 1997;349:971-7.
[116]. Lubsen J, Just H, Hjalmarsson AC, et al. Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial. Heart 1996; 76: 223-31.
[117]. Packer M, Carver JR, Rodeheffer RJ, et al, for the PROMISE Study Research Group. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468-75.
[118]. Elkayam U, Johnson JV, Shotan A, et al. Double-blind, placebocontrolled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition. Circulation 1999;99:2652-7.
[119]. Garg UC, Hassid A. Nitric oxide-generating vasodilators and 8- bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989;83:1774-7.
[120]. Calderone A, Thaik CM, Takahashi N, Chang DLF, Colucci WS. Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts. J Clin Invest 1998;101:812-8.
[121]. Jugdutt BI, Khan MI. Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction. Circulation 1994;89:2297-307.
[122]M aack C, Kartest, Kilter H, et al.Oxygen free radical release in human failing myocardium is associated with increased activity of racl-GTpase and represent sat ar get for statin treatment[J]. Circulation, 2003, 108: 1567-1574
[123]Ray JC, Gong Y, Sykora K, et al.Statin use and survival outcomes in elderly patients with heart failure.Arch intern Med, 2005, 165: 62-67
[124]Mozafarian D, Nye R, Levy WC.Statin therapy is associated with lower mortality among patients with server heart failure.Am[J]. Cardiol, 2004, 93: 1124-1129
[125]. Colucci WS, Elkayam U, Horton DP, et al, for the Nesiritide Study Group. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. N Engl J Med 2000; 343:246-53.
[126]. Elkayam U, Akhter MW, Singh H, Khan S, Usman A. Comparison of effects on left ventricular filling pressure of intravenous nesiritide and high-dose nitroglycerin in patients with decompensated heart failure. Am J Cardiol 2004;93:237-40.
[127]. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 2002;287:1531-40.
[128]. Goldsmith SR. Congestive heart failure: potential role of arginine vasopressin antagonists in the therapy of heart failure. Congest Heart Fail 2002;8:251-6.
[129]. Gheorghiade M, Niazi I, Ouyang J, et al. Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation 2003;107:2690-6.
[130]. Udelson JE, Smith WB, Hendrix GH, et al. Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation 2001; 104: 2417-23.
[131]. Gheorghiade M, Gattis WA, O'Connor CM, et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 2004;291:1963-71.
[132]. Russell SD, Selaru P, Pyne DA, et al. Rationale for use of an exercise end point and design for the ADVANCE (A Dose evaluation of a Vasopressin ANtagonist in CHF patients undergoing Exercise) trial. Am Heart J 2003;145:179-86.
[133]. Silverman ME, Pressel MD, Brackett JC, Lauria SS, Gold MR, Gottlieb SS. Prognostic value of the signal-averaged electrocardiogram and a prolonged QRS in ischemic and nonischemic cardiomyopathy. Am J Cardiol 1995;75:460-4.
[134]. Wilensky RL, Yudelman P, Cohen AI, et al. Serial electrocardiographic changes in idiopathic dilated cardiomyopathy confirmed at necropsy. Am J Cardiol 1988;62:276-83.
[135]. Grines CL, Bashore TM, Boudoulas H, Olson S, Shafer P, Wooley CF. Functional abnormalities in isolated left bundle branch block: the effect of interventricular asynchrony. Circulation 1989;79:845-53.
[136]. Xiao HB, Lee CH, Gibson DG. Effect of left bundle branch block on diastolic function in dilated cardiomyopathy. Br Heart J 1991;66:443-7.
[137]. Takeshita A, Basta LL, Kioschos JM. Effect of intermittent left bundle branch block on left ventricular performance. Am J Med 1974;56:251-5.
[138]. Xiao HB, Roy C, Fujimoto S, Gibson DG. Natural history of abnormal conduction and its relation to prognosis in patients with dilated cardiomyopathy. Int J Cardiol 1996;53:163-70.
[139]. Shamim W, Francis DP, Yousufuddin M, et al. Intraventricular conduction delay: a prognostic marker in chronic heart failure. Int J Cardiol 1999;70:171-8.
[140]. Unverferth DV, Magorien RD, Moeschberger ML, Baker PB, Fetters JK, Leier CV. Factors influencing the one-year mortality of dilated cardiomyopathy. Am J Cardiol 1984;54:147-52.
[141]. Blanc JJ, Etienne Y, Gilard M, et al. Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study. Circulation 1997;96:3273-7.
[142]. Kass DA, Chen CH, Curry C, et al. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 1999;99:1567-73.
[143].Toussaint JF,Lavergne T,Ollitraut J,et al.Biventricular pacing in severe heart failure patients reverses electromechanical dyssynchronization from apex to base.Pacing Clin Electrophysiol 2000;23:1731-4.
[144].Nelson GS,Berger RD,Fetics BJ,et al.Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundlebranch block.Circulation 2000;102:3053-9.
[145]Kaab S,Barth AS,Margerie D,etal.Global gene expression in human myocardium ol imgo nucleotide microarray analysis of regional diversity and transcriptional regulation in heart failure[J]。JMOLMed,2004,82(5):308-316
[146]Cowie MR,Mosterd A,Wood DA,et al.The epidemiology of heart failure.Eur Heart J,1999,18:208-225.
[147]John Cleland,Hull(UK),Henry Dargie,Glasgow(UK),Helmut Drexler,Hannover(Germany) etal.Guidelines for the diagnosis and treatment of chronic heart failure:executive summary(update 2005).European Heart Journal(2005)26,1115-1140
[148]中华医学会心血管病分会 中华心血管病杂志编辑委员会·慢性心力衰竭诊断治疗指南·中华心血管病杂志,2007,35(12):1076-1096
[149]Fletcher PJ,Pfeffer JM,Pfeffer MA.Left ventricular diastolic pressvolume relations in rats with healed myocardial infarction[J].Circulation Research,1981,49(3):618-627.
[150]McMurray JJ,Ray SG,Abdullah I et al.Plasma endothelin in chronic heart failure[J].Circulation 1992;85(4):1347-1379
[151]陈筱潮,徐明彤。心血管系统内分泌学[M].广州:中山大学出版社,2007.96-98,136-137
[152]McGregor DD·The effects of sympathetic nerve stimulation vasoconstrictor response in perfused mesenteric blood vessele of the rats·Physiology 1965;177:21.
[153]方泰惠·石斛对大鼠肠系膜的动脉血管的作用[J]·南京中医学院学报1991;7(2):100-101.
[154]孟伟栋,汪爱虎,孙宝贵。醛固酮及其拮抗剂在心力衰竭中的研究进展。国外医学心血管疾病分册2002;29(3);145-147
[155]Tokola H,Hautala V,Marttila M,et al.Mechanicall oad- induced alterations in B-type natriuretic peptide gene expression[J].Can J Physiol Parmaco,2001,79(8):646- 653.
[156]Ito T,Yoshimura M,Nakamura S,et ai.Inhibitory effect of natriuretic peptides on aidosterone synthase gene expression in cultured neonatal ratcardiocytes.Circulation,2003,107(6):807-810.
[157]Maisel A.B-type natriuretic peptid elevels:diagnostic and therapeutic potential.Cardiovasc Toxcol,2001,1(2):159-164.
[158]Kruger S,Graf J,Merx M,et al.Brain natriuretic peptide predicts right heart failure in patients with acute pulmonary embolism.Am Heart J,2004,147:60- 65.
[159]Leroyg,Uzanl,Bugugnanimj,et al.The value of repeated determination of brain natriuretic peptide for the diagnosis of unstable angina[J].Arch mal Coeur Vaiss,2003,96(4):305- 310.
[160]GuyattGH,SullivanMJ,ThompsonPJ,etal.The 6-minutewalk:anew measure of exercise capa city inpatients with chronic heart failure[J].CanMedAssocJ,1985,132:919-923.
[161]LipkinDP,ScrivenAJ,CrakeT,etal.Six-minute walking test for assessing exercise capa city in chronic heart failure[J].BrMedJ,1986,292:653-655.
[162]BittnerV,WeinerDH,YusufS,etal.Prediction of mortality and morbidity with a 6-minute walk test inpatients with left ventriculardy sfunction[J].JAMA,1993,270(14):1702-1707.
[163]侯云生,何国祥,何振山,等·黄芪对试验性急性心肌梗塞后心室重构的影响[J].现代中西医结合杂志,1999,8(12):1940-1941
[164]侯云生,何国祥,何振山,等·黄芪对急性心肌梗死后左室重构的治疗作用[J].心脏杂志,2000,12(4):270-272
[165]刘艳霞,刘在萍,焦建杰,等.黄芪苷Ⅳ对正常和心功能受抑制大鼠左心室心肌力学的影响[J].中草药,2001,32(4):332-334.
[166]周吉燕,樊懿,孔建龙,等.黄芪中不同提取成分对在体大鼠心肌缺血-再灌注损伤的心功能影响[J].中国中药杂志,2000,25(5):300-302.
[167]彭定风,柯丽,李论,等.黄芪对缺氧心肌细胞的保护作用[J].临床心血管病杂志,2003,19(4):234-236.
[168]何蕾.黄芪注射液抗心肌细胞再灌注损伤的作用及机制[J].世界急危重病医学杂志,2006,3(4):1366.
[169]程金波,卫洪昌,章忱,等.麦冬提取物抗犬心肌缺血的药效学实验研究[J].中国病理生理杂志,2001,17(8):810.
[170]顾双林,纪克.麦冬对实验性心肌梗塞及心肌缺血时亚微结构的影响[J].上海中医药杂志,1993,27(7):44-45.
[171]蒋凤荣,张旭,范俊,等.麦冬药理作用研究进展[J].中医药学刊,2006,24(2):236-237.
[172]范俊,张旭.麦冬对心脑血管系统药理作用研究进展[J].南京中医药大学学报,2006,22(4):270-272.
[173]王丽娟,王勇.麦冬药理作用与临床应用研究进展[J].中华医学研究杂志,2005,5(9):885-887.
[174]周跃华,徐德生,冯怡,等.麦冬提取物对小鼠心肌营养血流量的影响[J].中国实验方剂学杂志,2003,9(1):22-24.
[175]舒晓燕,侯大斌,阮期平.山茱萸的研究进展[J].中国药业,2007,16(10):60-62
[176]杨芳.蒲黄之药理[J]浙江中医学院学报,1998,22(1):49
[177]陈奇,陶子平,毕明等.心益好的药理研究[J].中草药1985;16(9):22
[178]Albertus J S.Medicinal and pharmaceutical uses ofseaweed natural products:A review.Journal of AppliedPhycology,2004,16:245-262.