Selective large coronary endothelial dysfunction in conscious dogs with chronic coronary pressure overload.
Selective large coronary endothelial dysfunction in conscious dogs with chronic coronary pressure overload.
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患有慢性冠状动脉压力超负荷的清醒犬的选择性大冠状动脉内皮功能障碍。
DOI：
10.1152/ajpheart.1998.274.2.h539
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Vatner,SF
中科院分区：
文献类型：
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作者：
Ghaleh,B;Hittinger,L;Kim,SJ;Kudej,RK;Iwase,M;Uechi,M;Berdeaux,A;Bishop,SP;Vatner,SF
本文观察了7只清醒犬和7只对照组犬冠状动脉对乙酰胆碱(ACh，3μg/kg iv)、硝酸甘油(NTg 25μg/kg iv)和20-S冠脉阻断(反应性充血)的反应。测量冠脉超声内径(CD)和多普勒冠脉血流量(CBF)。CCPO犬的LV/体重比增加82%。在对照组，ACh使Cd增加(+5.9±1.7%)。CCPO犬的这一反应降低(P<；0.05)(+1.9±0.9%)。同样，CCPO组(+2.1±0.8)与对照组(+6.8±1.8%)相比，RH后血流介导的CD增加被钝化(P<；0.01)。相反，ACh和RH在两组中增加的CBF相似。对照犬和CCPO犬的CD和CBF对NTG的增加无差异。冠脉血流峰值血流速度，慢性阻塞性肺疾病犬(94±17 cm/S)较对照组(35±7 cm/S)高(P<；0.01)，很可能是冠脉灌流压升高(215vs.130 mm Hg)所致。CCPO大冠状动脉的组织学分析显示内弹力板和内皮细胞中层增厚、内膜增厚和破裂。相反，心肌内小动脉不能显示内膜和内皮病变。因此，在选择性冠状动脉CCPO中，即不依赖于系统性高血压和血浆肾素活性升高的模型中，血流介导的和受体介导的大冠状动脉功能的内皮控制都受到了损害，这可以通过大冠状动脉的主要形态变化来解释，而不是阻力血管。其机制可能涉及慢性冠状动脉收缩压升高、CBF血流速度和潜在的层流模式中断。
Coronary vascular responses to acetylcholine (ACh, 3 μg/kg iv), nitroglycerin (NTG, 25 μg/kg iv), and a 20-s coronary artery occlusion (reactive hyperemia, RH) were investigated in seven conscious dogs with severe left ventricular (LV) hypertrophy and chronic coronary pressure overload (CCPO) due to supravalvular aortic banding and in seven control dogs. All dogs were instrumented for measurement of ultrasonic coronary diameter (CD) and Doppler coronary blood flow (CBF). LV-to-body weight ratio was increased by 82% in CCPO dogs. In control dogs, ACh increased CD (+5.9 ± 1.7%). This response was reduced (P< 0.05) in CCPO dogs (+1.9 ± 0.9%). Similarly, flow-mediated increases in CD after RH were blunted (P< 0.01) in CCPO (+2.1 ± 0.8) vs. control dogs (+6.8 ± 1.8%). In contrast, ACh and RH increased CBF similarly in both groups. Increases in both CD and CBF to NTG were not different between control dogs and CCPO. Peak systolic CBF velocity was greater,P< 0.01, in CCPO (94 ± 17 cm/s) compared with control (35 ± 7 cm/s) dogs, most likely secondary to the increased systolic coronary perfusion pressure (215 vs. 130 mmHg). Histological analyses of large coronary arteries in CCPO revealed medial thickening, intimal thickening, and disruption of the internal elastic lamina and endothelium. In contrast, small intramyocardial arterioles failed to show the intimal and endothelial lesions. Thus, in CCPO selective to the coronary arteries, i.e., a model independent from systemic hypertension and enhanced levels of plasma renin activity, endothelial control was impaired for both flow-mediated and receptor-mediated large coronary artery function, which could be accounted for by the major morphological changes in the large coronary arteries sparing the resistance vessels. The mechanism may involve chronically elevated systolic coronary perfusion pressure, CBF velocity, and potential disruption of laminar flow patterns.