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1、冠心病血管内皮保护的非药物干预方法 -体外反搏伍贵富 中山大学附属第一医院心内科 心血管康复中心 卫生部辅助循环重点实验室 2011.12.4 杭州A Novel Modality of Vascular Endothelial Protection: Enhanced External Counterpulsation2010-2030 中国CVD事件将 发生警报性增长（50%)WHO疾病负担项目Circulation. 2011; 124:314-323. Circulation. 2011; 124:278-279.中国心脑血管病防治面临挑战更为严峻！脑卒中死亡率冠心病死亡率Evolut
2、ion of Cardiovascular DiseasesRisk Factors Hypertension Atherogenic Dyslipidemia Diabetes Mellitus Abdominal Obesity Prothrombotic state Proinflammatory state Genetics Ethnic Predisposition Aging Hormonal imbalance Physical inactivity SmokingCommon Factors Exercise capacity Arterial wall thickening
3、Vascular Stiffness Atherosclerosis LV- contractility LV- relaxation Endothelial Dysfunction Inflammation Catabolism Atrophy Early fatigue Skeletal Muscle Dysfunction Ventilatory Abnormalities Neurohormonal activation Renal Single organ dysfunction Angina Heart Attack Stroke Silent IschemiaMultiple o
4、rgans dysfunction Heart failure Renal Failure Cerebral PulmonaryDisease ProgressionComplex factors that determine the rate of progression from risk to organ failureLinking risk factors to cardiovascular disease is endothelial dysfunction血流切应力与血管内皮保护生理状态的切应力低切应力状态低血流切应力和湍流区域 是动脉粥样硬化斑块高发区域血流切应力与冠心病的临床
5、联系体内反搏 （IABP）体外反搏 （ECP）辅助衰竭的心脏：从内反搏到外反搏增强型体外反搏工作原理 Enhanced External Counterpulsation, EECP时 间体外反搏发展的重要事件1980年代初增强型体外反搏装置（EECP）诞生并进入临床应用1990年代初EECP装置获美国FDA批准，进入美国并经此进入世界其他国家和地区1995-1997年 美国第一个体外反搏RCT（MUST-EECP）：哈佛大学、耶鲁大学、哥 伦比亚大学、纽约州立大学及加州州立大学等联合攻关 1998年第一个“国际EECP病人登记中心（IEPR）”（美国匹兹堡大学）2002年美国ACC/AHA冠
6、心病稳定型心绞痛治疗指南（IIb）2006年欧洲心脏病协会（ESC）冠心病心绞痛治疗指南(IIb)心血管病分会冠心病心绞痛治疗指南（IIb）2009年在中国老年学会的支持下，中国体外反搏专业委员会(EAC)成立增加心输出量Duplex echocardiography Descending AortaLawson, Hui: J of Critical Illness 2000;5:629-636 ControlEECP降低收缩期阻力负荷舒张期主动脉根 部血流增加增加CO增加静脉 回心血流增加心室舒 张期充盈收缩期舒张期降低收缩期 阻力负荷增加冠脉血流体外反搏对心脏血流的影响Bhavanand
7、a T. Reddy, Andrew D. Michaels Journal of Geriatric Cardiology 2010;7(2):67体外反搏与IABP比较的血流动力学差异舒张压 主动脉平均压收缩压 冠脉平均流速 舒张期冠脉流速Health Volunteer Atherosclerotic10203010200Change of blood velocity (%)收缩期流速舒张期平均流速-6.0%-19.3%*9.6%13.7%*3.2%23.6%*p0.05 , *p0.01体外反搏对其它重要脏器的影响-眼底动脉血流Werner D, et al: Graefes Arc
8、h Clin Exp Ophthalmol. 239:599-6-2健康志愿者 动脉粥样硬化颈动脉 (n=35)肾动脉 (n=18)Applebaum RM, et al: Am Heart J 1997;133:611-5.102030022% 19%p=0.001(%)p=0.0001血流速度积分变化率20406005640(cm/sec)舒张期平均流速体外反搏对其它重要脏器的影响-颈动脉、肾动脉ConfidentialNat Clin Pract Cardiovasc Med 2006;3(11):623-32Change in Angina Functional Class from
9、IEPR-1 Baseline CCS anginal Class Distribution1-year CCS anginal Class Distribution86% in Class III/IV25% in Class III/IV2719301960102030405060No AnginaIIIIIIIV% of patients in each CCS Class76% maintained at least 1 CCS class improvement 0102030405060IIIIIIIV% of patients in each CCS ClassN=4,56529
10、.718.427.817.96.2 0102030405060No anginaIIIIIIIV2-year CCS anginal Class Distribution24% in Class III/IVAm Journal of Cardiol 2004;93:461 - 4643-year CCS anginal Class Distribution0102030405060No Angina I IIIIIIV21% in Class III/IV5%16%24.8% 19.3%34.9%Clin.Cardiol 2008; 31,4:159 - 164ConfidentialCha
11、nges in patients with Left Ventricular DysfunctionWith diabetes mellitus (DM, n=36) versus non-diabetes (Non-DM, n=27)6-minute WalkNYHA Classification2.71.12.91.3p0.001p0.001p0.001p0.001Increase 37%Increase 30% No significant difference in the increase in both groupPre-EECPPost-EECP7478731,0251,137(
12、ft)AHA 2008ConfidentialChanges in patients with Left Ventricular DysfunctionWith diabetes mellitus (DM, n=36) versus non-diabetes (Non-DM, n=27) Cardiac Output3.13.93.34.1p0.001p0.001Pre-EECPPost-EECP0510152025303540DMNon-DMEjection Fractionp0.001p0.001Increase 21%Increase 20% No significant differe
13、nce in the increase in both group29.829.936.235.9(%)(l/min)Increase 25%Increase 22% No significant difference in the increase in both groupAHA 2008Cost effectivenessPotential Cost Savings Scenario# HF ptsTotal # Hospital VisitsAverage Cost per Hospital Visit Total Cost to Healthcare System /1,000 pt
14、s Before ECP1, 0003,000*$5,456$16,368,000 After ECP1,000500*$5,456$2,728,000 Reduction in hospitalization costs after treated with ECP$13,640,000Cost to treat with ECP $3,640,000 Annual savings to healthcare $10,000,000 Saving per patient$10,000*Average # of hospital visits before ECP over 12 months
15、 is 3.6 * Average # of hospital visits after ECP over 12 months is 0.5(Reduction in average cost of hospitalizations)EECP reduced ER Visits 13:36-4000.20.40.60.811.21.486% 83% 6-months Pre-EECP6-months Post- EECPp0.001p0.001ER Visits6-months Pre-EECP6-months Post- EECP3.53.02.52.01.51.00.50流流 速速切应力切
16、应力体外反搏对猪颈总动脉内的血液流速和切应力变化0.89%9.18%2.17%0246810正常组高脂组反搏组AS+体外反搏AS正常对照体外反搏对实验动物（猪）动脉硬化的影响Zhang Y, et al: Circulation 2007,116:526-34体外反搏治疗对实验性动脉粥样硬化猪冠脉内膜的影响Zhang Y, et al: Circulation 2007, 116: 526-34Confidentialx400x40正常组动脉硬化组动脉硬化组体外反搏体外反搏保护血管内膜促进冠状动脉血管重构HE染色弹力纤微染色Zhang Y, et al: Circulation 2007, 116: 526-34体外反搏降低冠脉前降支CRP和补体C3a表达Zhang Y, et al: ATVB 2010Tao J, et al: International Journal of Cardiology 2006, 112:269-274 体外反搏治疗改善高胆固醇血症猪 内皮依赖的血管舒张功能（离体动脉环）Cardiolo
