Kortekaas Kirsten A, de Vries Dorottya K, Roest Mark, Reinders Marlies Ej, van der Veer Eric P, Klautz Robert Jm, de Groot Philip G, Schaapherder Alexander F, Lindeman Jan H
Department of Cardiothoracic Surgery, Leiden University Medical CenterLeiden, The Netherlands.
Department of Cardiology, OLVG OostAmsterdam, The Netherlands.
Am J Transl Res. 2018 Mar 15;10(3):816-826. eCollection 2018.
The pathophysiology of ischemia/reperfusion (I/R) injury is complex and poorly understood. Animal studies imply platelet activation as an initiator of the inflammatory response upon reperfusion. However, it remains unclear whether and how these results translate to clinical I/R. This study evaluates putative platelet activation in the context of two forms of clinical I/R (heart valve surgery with aortic-cross clamping, n = 39 and kidney transplantation, n = 34). The technique of sequential selective arteriovenous (AV) measurements over the reperfused organs was applied to exclude the influence of systemic changes occurring during surgery while simultaneously maximizing sensitivity. Platelet activation and degranulation was evaluated by assessing the expression levels of established markers, i.e. RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), β-thromboglobulin (β-TG), platelet-derived growth factor (PDGF)-BB and CXCL8 (known as interleukin-8), and by employing an in-vitro assay that specifically tests for platelet excitability. Moreover, a histological analysis was performed by means of CD41 staining. Results show stable RANTES, β-TG, PDGF-BB and CXCL8 AV-concentrations within the first half hour over the reperfused organs, suggesting that myocardial and renal I/R are not associated with platelet activation. Results from the platelet excitability assay were in line with these findings and indicated reduced and stable platelet excitability following renal and myocardial reperfusion, respectively. Histological analysis yield evidence of platelet marginalization in the reperfused organs. In conclusion, results from this study do not support a role for platelet activation in early phases of clinical I/R injury.
缺血/再灌注（I/R）损伤的病理生理学复杂且尚未完全明晰。动物研究表明血小板激活是再灌注时炎症反应的启动因素。然而，这些结果能否以及如何转化至临床I/R仍不明确。本研究评估了两种临床I/R形式（主动脉交叉钳夹心脏瓣膜手术，n = 39；肾移植，n = 34）情况下假定的血小板激活情况。采用对再灌注器官进行连续选择性动静脉（AV）测量的技术，以排除手术期间发生的全身变化的影响，同时使敏感性最大化。通过评估既定标志物即调节激活正常T细胞表达和分泌的趋化因子（RANTES）、β-血小板球蛋白（β-TG）、血小板衍生生长因子（PDGF）-BB和CXCL8（即白细胞介素-8）的表达水平，并采用专门检测血小板兴奋性的体外试验，来评估血小板激活和脱颗粒情况。此外，通过CD41染色进行组织学分析。结果显示，再灌注器官在最初半小时内RANTES、β-TG、PDGF-BB和CXCL8的AV浓度稳定，这表明心肌和肾I/R与血小板激活无关。血小板兴奋性试验的结果与这些发现一致，表明肾和心肌再灌注后血小板兴奋性分别降低且稳定。组织学分析得出了再灌注器官中血小板边缘化的证据。总之，本研究结果不支持血小板激活在临床I/R损伤早期阶段发挥作用。
