Akkoca Muzaffer, Usanmaz Suzan Emel, Tokgöz Serhat, Köksoy Cüneyt, Demirel-Yilmaz Emine
Department of General Surgery, Dışkapı Research and Training Hospital, University of Health Sciences, Altındağ, Ankara, Turkey.
Department of Medical Pharmacology, Faculty of Medicine, Ankara University, Sıhhiye, Ankara, Turkey.
Clin Hemorheol Microcirc. 2018;70(1):83-93. doi: 10.3233/CH-170337.
Intermittent ischemia in remote tissues can be applied before ischemic injury, during ischemic injury or at the beginning of reperfusion of an index organ ischemia. The aim of this study was to investigate the effect of Remote Ischemic Conditioning (RIC) of the leg on changes in ischemia-induced the microvascular functions of the arm.
Ischemic microvascular injury was induced by arm ischemia (20 min) and reperfusion in healthy, nonsmoker, male volunteers (ischemia group-ISC, n: 9). In another group of volunteers, to investigate the effects of remote organ ischemic conditioning 5 cycles of reperfusion followed by leg ischemia (each lasting 60 seconds) were applied either before (preRIC, n:11), or during (perRIC, n:12) or immediately after (postRIC, n:9) 20 minutes of arm ischemia. The microvascular flow of arm was assessed before and after ischemia using iontophoresis of the endothelium-derived nitric oxide (NO) releaser acetylcholine (ACh) and the endothelium-independent NO donor sodium nitroprusside (SNP). Changes in microvascular blood flow were measured using Laser Doppler imaging. The plasma level of biomarkers related to endothelial function such as nitric oxide (NO), asymmetric dimethylarginine (ADMA), total antioxidant capacity (TAC) and hydrogen sulphide (H2S) were measured.
No difference was determined between the groups in terms of age, BMI or blood biochemicals reflecting cardiovascular status. ACh caused a rise in microvascular blood flow in a charge dependent manner. The ACh-induced flow increase was not significantly depressed by ischemia and not affected by any of the types of RIC in the study subjects. The increase in SNP-induced microvascular flow was significantly decreased in the ISC, perRIC and postRIC groups, but not in the preRIC group. Plasma levels of NO, ADMA, TAC and H2S were not changed by ischemia and RIC.
These results suggested that microvascular perfusion of human forearm skin was elevated by either endothelium or drug-derived NO. The effect of ischemia and RIC on NO-induced flow increase was affected differently by different applications in the healthy young individuals. These complicated results are taken into consideration in experimental and therapeutic interventions.
远处组织的间歇性缺血可在缺血性损伤前、缺血性损伤期间或靶器官缺血再灌注开始时应用。本研究的目的是探讨腿部远程缺血预处理（RIC）对缺血诱导的手臂微血管功能变化的影响。
在健康、不吸烟的男性志愿者中，通过手臂缺血（20分钟）和再灌注诱导缺血性微血管损伤（缺血组-ISC，n = 9）。在另一组志愿者中，为了研究远处器官缺血预处理的效果，在手臂缺血20分钟之前（预处理RIC，n = 11）、期间（处理中RIC，n = 12）或之后立即（处理后RIC，n = 9），施加5个周期的再灌注，随后进行腿部缺血（每次持续60秒）。使用内皮源性一氧化氮（NO）释放剂乙酰胆碱（ACh）和非内皮依赖性NO供体硝普钠（SNP）的离子电渗法，在缺血前后评估手臂的微血管血流。使用激光多普勒成像测量微血管血流的变化。测量与内皮功能相关的生物标志物的血浆水平，如一氧化氮（NO）、不对称二甲基精氨酸（ADMA）、总抗氧化能力（TAC）和硫化氢（H2S）。
在年龄、体重指数或反映心血管状态的血液生化指标方面，各组之间未发现差异。ACh以电荷依赖的方式引起微血管血流增加。在研究对象中，ACh诱导的血流增加未因缺血而显著降低，也不受任何类型的RIC影响。在ISC组、处理中RIC组和处理后RIC组中，SNP诱导的微血管血流增加显著降低，但预处理RIC组未降低。缺血和RIC未改变NO、ADMA、TAC和H2S的血浆水平。
这些结果表明，内皮或药物源性NO均可提高人前臂皮肤的微血管灌注。在健康年轻个体中，不同的应用方式对缺血和RIC对NO诱导的血流增加的影响不同。在实验和治疗干预中应考虑这些复杂的结果。
