Neumann F J, Ott I, Gawaz M, Richardt G, Holzapfel H, Jochum M, Schömig A
Medizinische Klinik, Technischen Universität, München, Germany.
Circulation. 1995 Aug 15;92(4):748-55. doi: 10.1161/01.cir.92.4.748.
In animal models of myocardial infarction (MI), inflammatory responses compromise microcirculation during reperfusion and restrict functional recovery. To investigate cardiac inflammatory responses in patients with acute MI, we examined the cardiac release of cytokines, the expression on neutrophils of the beta 2-integrin Mac-1 (CD11b/CD18) and L-selectin (CD62L), and the cardiac release of thrombomodulin as a marker of endothelial injury.
In 12 patients with acute anterior MI, blood samples were obtained from the coronary sinus and from the aorta immediately before and after recanalization of the coronary occlusion by balloon angioplasty. Twelve patients undergoing elective balloon angioplasty served as control subjects. Plasma concentrations of interleukin (IL)-1 beta, IL-6, IL-8, tumor necrosis factor-alpha, and thrombomodulin were determined by immunoassay, and surface expression of CD11b and CD62L was assessed by flow cytometry. Differences in coronary sinus and arterial blood were found in IL-6 before (median, 6.3 ng/L, P = .01) and after (13.4 ng/L, P = .002) recanalization and in IL-8 after recanalization (10.7 ng/L, P = .02). The cardiac release of both cytokines significantly (P < or = .03) increased with reperfusion. Cytokine release after reperfusion was associated with significant transcardiac gradients in surface expression on neutrophils of CD11b (10.1 mean channel of fluorescence intensity [mean fl], P = .01) and CD62L (-87 mean fl, P = .007) and with a thrombomodulin release (4.5 micrograms/L, P = .004). Transcardiac gradients in IL-1 beta and tumor necrosis factor-alpha were not found. None of the changes found in MI were detectable in the control group.
As evidence of cardiac inflammatory responses in reperfused acute MI, the study demonstrates cardiac neutrophil activation with signs of endothelial injury and a release of the proinflammatory cytokines IL-8 and IL-6. These findings may assist in the design of pharmacological interventions aimed at reducing microvascular reperfusion injury.
在心肌梗死（MI）动物模型中，炎症反应会在再灌注期间损害微循环并限制功能恢复。为了研究急性MI患者的心脏炎症反应，我们检测了细胞因子的心脏释放、中性粒细胞上β2整合素Mac-1（CD11b/CD18）和L-选择素（CD62L）的表达，以及作为内皮损伤标志物的血栓调节蛋白的心脏释放。
在12例急性前壁MI患者中，在通过球囊血管成形术使冠状动脉闭塞再通之前和之后，立即从冠状窦和主动脉采集血样。12例行择期球囊血管成形术的患者作为对照。通过免疫测定法测定血浆白细胞介素（IL）-1β、IL-6、IL-8、肿瘤坏死因子-α和血栓调节蛋白的浓度，并通过流式细胞术评估CD11b和CD62L的表面表达。再通前（中位数，6.3 ng/L，P = 0.01）和再通后（13.4 ng/L，P = 0.002）IL-6以及再通后IL-8（10.7 ng/L，P = 0.02）在冠状窦血和动脉血中存在差异。随着再灌注，两种细胞因子的心脏释放均显著增加（P≤0.03）。再灌注后细胞因子的释放与中性粒细胞表面CD11b（荧光强度平均通道数[平均fl]为10.1，P = 0.01）和CD62L（-87平均fl，P = 0.007）表达的显著跨心脏梯度以及血栓调节蛋白释放（4.5μg/L，P = 0.004）相关。未发现IL-1β和肿瘤坏死因子-α的跨心脏梯度。在对照组中未检测到MI中发现的任何变化。
作为再灌注急性MI中心脏炎症反应的证据，该研究证明了心脏中性粒细胞激活伴有内皮损伤迹象以及促炎细胞因子IL-8和IL-6的释放。这些发现可能有助于设计旨在减少微血管再灌注损伤的药物干预措施。
