Huggins G S, Pasternak R C, Alpert N M, Fischman A J, Gewirtz H
Departments of Medicine (Cardiac Unit), Radiology, and Nuclear Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Circulation. 1998 Sep 29;98(13):1291-6. doi: 10.1161/01.cir.98.13.1291.
We tested the hypothesis that correction of hyperlipidemia improves coronary vasodilator response and maximal perfusion in myocardial regions having substantial impairment of pretreatment vasodilator capacity.
Measurements of myocardial blood flow were made with PET [13N]ammonia in 12 patients with ischemic heart disease (11 men; age, 65+/-8 years [mean+/-SD]) at rest and during adenosine at 70 and then 140 microg . kg-1 . min-1 for 5 minutes each before and approximately 4 months after simvastatin treatment (40 mg daily). Simvastatin reduced LDL (171+/-13 before versus 99+/-18 mg/dL after simvastatin, P<0.001) and increased HDL (39+/-8 versus 45+/-9 mg/dL, P<0.05). Myocardial segments were classified on the basis of pretreatment blood flow response to 140 microg . kg-1 . min-1 adenosine as normal (flow >/=2 mL . min-1 . g-1) or abnormal (flow <2 mL . min-1 . g-1). In normal segments, baseline myocardial blood flow (0.95+/-0.32) increased (P<0.001) at both low- (1.62+/-0.81) and high- (2.63+/-0.41) dose adenosine and was unchanged both at rest and with adenosine after simvastatin. In abnormal segments, myocardial blood flow at rest (0. 73+/-0.19) increased at low- (1.06+/-0.59, P<0.02) and high- (1. 29+/-0.33, P<0.01) dose adenosine. After simvastatin, myocardial blood flow increased more compared with pretreatment at both low- (1. 37+/-0.66, P<0.05 versus pretreatment) and high- (1.89+/-0.79, P<0. 01 versus pretreatment) dose adenosine.
Short-term lipid-lowering therapy increases stenotic segment maximal myocardial blood flow by approximately 45%. The mechanism involves enhanced, flow-mediated dilation of stenotic epicardial conduit vessels and may account at least in part for the efficacy of lipid lowering in secondary prevention trials and in reducing ischemic episodes in ambulatory patients.
我们检验了这样一个假设，即纠正高脂血症可改善冠状动脉血管舒张反应以及预处理血管舒张能力严重受损心肌区域的最大灌注。
对12例缺血性心脏病患者（11例男性；年龄65±8岁[平均值±标准差]）在静息状态下以及使用腺苷时（分别为70和140μg·kg-1·min-1，每次持续5分钟），采用正电子发射断层扫描（PET）[13N]氨测量心肌血流量，测量时间分别在辛伐他汀治疗前（每日40mg）和治疗后约4个月。辛伐他汀降低了低密度脂蛋白（治疗前为171±13，治疗后为99±18mg/dL，P<0.001）并升高了高密度脂蛋白（39±8对45±9mg/dL，P<0.05）。根据预处理时对140μg·kg-1·min-1腺苷的血流反应，将心肌节段分为正常（血流≥2mL·min-1·g-1）或异常（血流<2mL·min-1·g-1）。在正常节段，基线心肌血流量（0.95±0.32）在低剂量（1.62±0.81）和高剂量（2.63±0.41）腺苷时均增加（P<0.001），且在静息状态下以及辛伐他汀治疗后使用腺苷时均无变化。在异常节段，静息时心肌血流量（0.73±0.19）在低剂量（1.06±0.59，P<0.02）和高剂量（1.29±0.33，P<0.01）腺苷时增加。辛伐他汀治疗后，在低剂量（1.37±0.66，与治疗前相比P<0.05）和高剂量（1.89±0.79，与治疗前相比P<0.01）腺苷时，心肌血流量相较于治疗前增加得更多。
短期降脂治疗可使狭窄节段的最大心肌血流量增加约45%。其机制包括狭窄的心外膜导管血管的血流介导性扩张增强，这可能至少部分解释了降脂在二级预防试验中的疗效以及在减少门诊患者缺血发作方面的作用。
