Repeated dipyridamole administration enhances collateral-dependent flow and regional function during exercise. A role for adenosine.
Repeated dipyridamole administration enhances collateral-dependent flow and regional function during exercise. A role for adenosine.
复制标题
重复使用双嘧达莫可增强运动期间的侧支依赖性血流和区域功能。
DOI：
10.1161/01.res.73.3.503
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发表时间：
1993
影响因子：
20.1
通讯作者：
Longhurst,JC
中科院分区：
文献类型：
--
作者：
Symons,JD;Firoozmand,E;Longhurst,JC
关于冠状动脉侧支循环增长机制的两个主要假说表明，化学或机械因素参与其中。由于我们最近证实冠状动脉侧支循环的发展与心肌缺血的程度或持续时间没有密切的关系，我们假设使用潘生丁的慢性重复血管扩张和心肌血流量增加将促进左回旋支(LCx)闭塞的小型猪的侧支循环发展。术后两天分别给予双嘧达莫(n=9)、地尔硫卓(n=8)或对照组(n=7)，每日90分钟，每周5天，共8周。在5周和8周时，在注射双嘧达莫、地尔硫卓或赋形剂的过程中测量跨壁血流量和收缩期壁增厚。在输注任何一种血管扩张剂期间，30分钟和60分钟时，Lcx和非闭塞区域的跨壁血流量增加相似。因此，我们认为双嘧达莫和地尔硫卓输注产生了类似的机械刺激。在给药期间，血液流动没有变化。侧支依赖区域的收缩期壁增厚不会因潘生丁、地尔硫卓或赋形剂的注射而改变。因此，这两种血管扩张剂在不引起缺血的情况下增加了血流量。在每种药物重复治疗8周后，在最后一次药物注射后至少24小时，在跑步机跑步时评估冠脉侧支血管的接近最大生理容量(约240次/分钟)。在静息状态下，服用双嘧达莫(0.90+/-0.03)、地尔硫卓(0.97+/-0.05)和对照组(0.89+/-0.02)的动物，跨壁心肌血流量比率(Lcx中的流量除以左心室非闭塞区的流量)相似。然而，运动中侧支依赖的心肌血流量，双嘧达莫组(0.78+/-0.04)大于地尔硫卓组(0.63+/-0.09)或赋形剂组(0.62+/-0.02)。服用潘生丁(44.4+/-6.3%)、地尔硫卓(42.2+/-3.0%)和对照组(38.1+/-2.8%)的动物在静息状态下Lcx收缩期壁增厚相似。然而，在运动中，服用双嘧达莫的受试者侧支依赖区的心肌功能(P<；0.05)高于服用地尔硫卓的受试者(23.9±4.0%)和服用安慰剂的受试者(26.9±2.9%)(P<；0.05)。
Two main hypotheses concerning the mechanisms responsible for coronary collateral growth suggest the involvement of chemical or mechanical factors. Since we recently demonstrated that the development of the coronary collateral circulation is not closely related to the extent or duration of myocardial ischemia, we hypothesized that chronic repeated vasodilation and increased myocardial blood flow using dipyridamole would enhance collateral development in miniswine with an ameroid-occluded left circumflex coronary artery (LCx). Two days after surgical instrumentation, the animals received dipyridamole (n = 9), diltiazem as an adenosine-independent vasodilator (n = 8), or control vehicle (n = 7) 90 minutes per day, 5 days per week for 8 weeks. At 5 and 8 weeks, transmural blood flow and systolic wall thickening were measured during infusion of dipyridamole, diltiazem, or vehicle. Transmural blood flow increased similarly in the LCx and nonoccluded regions at 30 and 60 minutes during infusion of either vasodilator. Thus, we believe that similar mechanical stimulation resulted from dipyridamole and diltiazem infusion. There was no change in blood flow during administration of the vehicle. Systolic wall thickening in the collateral-dependent region was not altered by infusion of dipyridamole, diltiazem, or vehicle. Therefore, both vasodilators increased blood flow without eliciting ischemia. After 8 weeks of repeated treatment with each pharmacological agent, at least 24 hours after the last drug infusion, near maximal physiological capacity of the coronary collateral vessels was assessed during treadmill running (approximately 240 beats per minute). Transmural myocardial blood flow ratios, expressed as flow in the LCx divided by flow in the nonoccluded region of the left ventricle, were similar at rest for animals treated with dipyridamole (0.90 +/- 0.03), diltiazem (0.97 +/- 0.05), and control vehicle (0.89 +/- 0.02). However, collateral-dependent myocardial blood flow during exercise was greater (P < .05) in the dipyridamole-treated animals (0.78 +/- 0.04) than in either diltiazem-treated (0.63 +/- 0.09) or vehicle-treated (0.62 +/- 0.02) animals. LCx systolic wall thickening at rest was similar in animals treated with dipyridamole (44.4 +/- 6.3%), diltiazem (42.2 +/- 3.0%), and control vehicle (38.1 +/- 2.8%). During exercise, however, myocardial function in the collateral-dependent region was greater (P < .05) in the dipyridamole-treated (39.2 +/- 5.2%) compared with diltiazem-treated (23.9 +/- 4.0%) and vehicle-treated (26.9 +/- 2.9%) animals.(ABSTRACT TRUNCATED AT 400 WORDS)