停搏后未控制的糖尿病患者的冠状动脉微血管反应性降低。
Decreased coronary microvascular reactivity after cardioplegic arrest in patients with uncontrolled diabetes mellitus.
机构信息
Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
出版信息
Surgery. 2012 Aug;152(2):262-9. doi: 10.1016/j.surg.2012.04.009.
BACKGROUND
We investigated the effects of cardioplegic arrest and reperfusion on coronary arteriolar responses to endothelium-dependent and -independent vasodilators and associated signaling pathways in uncontrolled diabetic, well controlled diabetic, and case-matched nondiabetic patients undergoing coronary artery bypass graft surgery.
METHODS
Coronary arterioles from harvested right atrial tissues were dissected pre- and post-cardioplegic arrest and reperfusion from uncontrolled diabetic (n = 10; hemoglobin A1c = 9.3 ± 0.3), well controlled diabetic (n = 10; hemoglobin A1c = 6.2 ± 0.2), and nondiabetic patients (n = 10; hemoglobin A1c = 5.1 ± 0.1) undergoing coronary artery bypass graft surgery.
RESULTS
The baseline microvascular response to adenosine 5'-diphosphate, substance P, and sodium nitroprusside of arterioles from uncontrolled diabetic patients were decreased compared to the respective response from nondiabetic or well controlled diabetic patients (P < .05). The vasodilatory responses to adenosine 5'-diphosphate and substance P after cardioplegic arrest and reperfusion were significantly decreased in all 3 groups compared to pre-cardioplegic arrest and reperfusion responses (P < .05). However, these decreases were more pronounced in the uncontrolled diabetic group (P < .05). The expression of protein kinase C-α, protein kinase C-β, and protein oxidation in atrial tissues was significantly increased in the uncontrolled diabetic group compared to the nondiabetic or controlled diabetes groups.
CONCLUSION
Uncontrolled diabetes is associated with endothelium-dependent and -independent vascular dysfunction of coronary arterioles. In addition, uncontrolled diabetes worsens the recovery of coronary arteriolar function after cardioplegic arrest and reperfusion. These alterations are associated with an increased expression/activation of protein kinase C-α and protein kinase C-β and enhanced oxidative stress.
背景
我们研究了心脏停搏和再灌注对未经控制的糖尿病、良好控制的糖尿病和匹配病例的非糖尿病患者行冠状动脉旁路移植术时冠状动脉小动脉对内皮依赖性和非内皮依赖性血管扩张剂的反应以及相关信号通路的影响。
方法
从未经控制的糖尿病（n=10；糖化血红蛋白 A1c=9.3±0.3）、良好控制的糖尿病（n=10；糖化血红蛋白 A1c=6.2±0.2）和非糖尿病患者（n=10；糖化血红蛋白 A1c=5.1±0.1）行冠状动脉旁路移植术时取出的右心房组织中分离出心脏停搏和再灌注前后的冠状动脉小动脉。
结果
与非糖尿病或良好控制的糖尿病患者相比，未经控制的糖尿病患者的小动脉对腺苷 5'-二磷酸、P 物质和硝普钠的基础微血管反应降低（P<.05）。与心脏停搏和再灌注前的反应相比，所有 3 组的小动脉对腺苷 5'-二磷酸和 P 物质的血管舒张反应在心脏停搏和再灌注后均显著降低（P<.05）。然而，在未经控制的糖尿病组中，这些降低更为明显（P<.05）。与非糖尿病或控制糖尿病组相比，未经控制的糖尿病组心房组织中蛋白激酶 C-α、蛋白激酶 C-β 和蛋白氧化的表达显著增加。
结论
未经控制的糖尿病与冠状动脉小动脉的内皮依赖性和非依赖性血管功能障碍有关。此外，未经控制的糖尿病会加重心脏停搏和再灌注后冠状动脉小动脉功能的恢复。这些改变与蛋白激酶 C-α和蛋白激酶 C-β的表达/激活增加以及氧化应激增强有关。
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