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Impaired Coronary Endothelial Vasorelaxation in a Preclinical Model of Peripheral Arterial Insufficiency 外周动脉功能不全的临床前模型中冠状动脉内皮血管松弛受损
Pub Date : 2015-06-29 DOI: 10.15436/2378-6914/15/010
A. Arce-Esquivel, A. Bunker, G. Simmons, H. Yang, M. Laughlin, R. Terjung
The present study was designed to determine whether adult swine with peripheral artery insufficiency (PAI) would exhibit vascular dysfunction in vessels distinct from the affected distal limbs, the coronary conduit arteries. Moreover, we sought to evaluate the effect of exercise training on coronary vasomotor function in PAI. Eighteen female healthy young Yucatan miniature swine were randomly assigned to either occluded exercise trained (Occl-Ex, n=7), or occluded-sedentary (Occl-Sed, n=5), or non-occluded, non-exercised control (Non-Occl-Con, n=6) groups. Occl-Ex pigs were progressively trained by running on a treadmill (5days/week, 12 weeks). The left descending artery (LAD) and left circumflex (LCX) coronary arteries were harvested. Vasorelaxation to adenosine diphosphate (ADP), bradykinin (BK), and sodium nitro-prusside (SNP) were assessed in LAD’s; while constrictor responses to phenylephrine (PE), angiotensin II (Ang II), and endothelin-1 (ET-1) were assessed in LCX’s. Vasorelaxation to ADP was reduced in LADs from Occl-Sed and Occl-Ex pigs (P<0.001) as compared to Non-Occl-Con pigs; however, Occl-Ex pigs exhibited partial recovery (P<0.001) intermediate to the other two groups. BK induced relaxation was reduced in LADs from Occl-Ex and Occl-Sed pigs (P<0.001), compared to Non-Occl-Con, and exercise modestly increased responses to BK (P<0.05). In addition, SNP, PE, Ang II, and ET-1 responses were not significantly different among the groups. Our results indicate that ‘simple’ occlusion of the femoral arteries induces vascular dysfunction in conduit vessels distinct from the affected hindlimbs, as evident in blunted coronary vasorelaxation responses to ADP and BK. These findings imply that PAI, even in the absence of frank atherogenic vascular disease, contributes to vascular dysfunction in the coronary arteries that could exacerbate disease outcome in patients with peripheral artery disease. Further, regular daily physical activity partially recovered the deficit observed in the coronary arteries.
本研究旨在确定外周动脉功能不全(PAI)的成年猪是否会表现出与远端肢体不同的血管(冠状动脉导管)的血管功能障碍。此外,我们试图评估运动训练对PAI患者冠状动脉血管舒缩功能的影响。18头健康的尤卡坦小型母猪被随机分配到闭塞运动训练组(闭塞-ex组,n=7)、闭塞-不运动组(闭塞-sed组,n=5)或非闭塞、不运动对照组(non- closed - con组,n=6)。闭塞ex猪通过跑步机逐步训练(每周5天,12周)。取左降支(LAD)和左旋冠状动脉(LCX)。评估LAD患者对二磷酸腺苷(ADP)、缓激肽(BK)和硝普钠(SNP)的血管松弛;同时评估LCX对苯肾上腺素(PE)、血管紧张素II (Ang II)和内皮素-1 (ET-1)的收缩反应。与未闭塞的猪相比,闭塞猪和闭塞猪的血管松弛对ADP的影响降低(P<0.001);然而,闭塞ex猪表现出部分恢复(P<0.001),介于其他两组之间。与未闭塞猪相比,闭塞猪和闭塞猪的lad中BK诱导的松弛减少(P<0.001),运动适度增加了对BK的反应(P<0.05)。此外,SNP、PE、Ang II和ET-1的反应在组间无显著差异。我们的研究结果表明,股动脉“单纯”闭塞导致导管血管功能障碍,与后肢不同,这一点在ADP和BK引起的冠状动脉血管松弛反应减弱中是显而易见的。这些发现表明,即使在没有明显的动脉粥样硬化性血管疾病的情况下,PAI也会导致冠状动脉血管功能障碍,从而加剧外周动脉疾病患者的疾病结局。此外,有规律的日常体育活动部分地恢复了冠状动脉的缺陷。
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Journal of heart and cardiology
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