Kim S J, Ghaleh B, Kudej R K, Huang C H, Hintze T H, Vatner S F
Department of Medicine, Harvard Medical School, Boston, Mass., USA.
Circ Res. 1997 Jul;81(1):53-9. doi: 10.1161/01.res.81.1.53.
The goal of this study was to determine both the early and delayed effects of a brief (10-minute) coronary artery occlusion (CAO) and prolonged (5-day) reperfusion (CAR) on coronary endothelial function. Fourteen mongrel dogs were chronically instrumented to measure aortic and left ventricular pressures, wall thickness, and left circumflex coronary blood flow (CBF). Before CAO and during CAR, coronary vascular reactivity was investigated by 15-second CAO and subsequent reactive hyperemia (RH) and by the selective intracoronary infusion of acetylcholine (ACh, 10 micrograms/min) and bradykinin (BK, 2.5 micrograms/min), endothelium-dependent vasodilators, and sodium nitroprusside (SNP, 40 micrograms/min), an endothelium-independent vasodilator. CBF responses to ACh and BK began to increase after 6 hours of CAR, reached a peak after 1 to 2 days of CAR, and then subsided over the subsequent 4 days. After 1 day of CAR, compared with before CAO, enhanced CBF responses (P < .05), associated with increased coronary sinus oxygen content, were observed for-ACh (+66 +/- 20%), BK (+74 +/- 24%), and RH (+24 +/- 5%) but not SNP (-2 +/- 10%). Production of NO metabolites (nitrate and nitrite), measured as their coronary arteriovenous differencexCBF, was significantly increased after 1 to 2 days of CAR, both at baseline (153 +/- 56%) and during BK infusion (220 +/- 76%) (P < .05). Holding CBF at pre-CAO levels during the initial CAR period did not attenuate the delayed enhanced endothelial vasodilation to ACh and BK. However, NO blockade with intracoronary NG-nitro-L-arginine blocked the enhanced coronary vasodilation to ACh and BK. Thus, in contrast to previous studies, these data indicate that brief ischemic episodes induce delayed enhanced coronary endothelial function, which is delayed in onset and prolonged in duration. This can be explained by an upregulation of coronary vascular NO production, potentially involved in the mechanism of the delayed window of preconditioning.
本研究的目的是确定短暂（10分钟）冠状动脉闭塞（CAO）和延长（5天）再灌注（CAR）对冠状动脉内皮功能的早期和延迟影响。对14只杂种犬进行长期仪器植入，以测量主动脉和左心室压力、壁厚度以及左旋支冠状动脉血流量（CBF）。在CAO之前和CAR期间，通过15秒的CAO及随后的反应性充血（RH），以及通过选择性冠状动脉内注入内皮依赖性血管舒张剂乙酰胆碱（ACh，10微克/分钟）和缓激肽（BK，2.5微克/分钟），和内皮非依赖性血管舒张剂硝普钠（SNP，40微克/分钟）来研究冠状血管反应性。CAR 6小时后，CBF对ACh和BK的反应开始增加，CAR 1至2天后达到峰值，然后在随后4天内消退。CAR 1天后，与CAO前相比，观察到ACh（+66±20%）、BK（+74±24%）和RH（+24±5%）的CBF反应增强（P<.05），且伴有冠状窦氧含量增加，但SNP（-2±10%）无此现象。以冠状动脉动静脉差xCBF来衡量的NO代谢产物（硝酸盐和亚硝酸盐）的生成在CAR 1至2天后显著增加，在基线时（153±56%）和BK输注期间（220±76%）均如此（P<.05）。在初始CAR期间将CBF维持在CAO前水平并不能减弱对ACh和BK的延迟增强的内皮血管舒张作用。然而，冠状动脉内注入NG-硝基-L-精氨酸进行NO阻断可阻断对ACh和BK的增强的冠状动脉血管舒张作用。因此，与先前的研究相反，这些数据表明短暂缺血发作可诱导延迟增强的冠状动脉内皮功能，其发作延迟且持续时间延长。这可以通过冠状动脉血管NO生成的上调来解释，这可能参与了延迟预适应机制。
