Sharma Madhulika, Ganguly Nirmal Kumar, Chaturvedi Gaurav, Thingnam Shyam K S, Majumdar Siddhartha, Suri Rajendar Krishan
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
Mol Cell Biochem. 2003 May;247(1-2):23-30. doi: 10.1023/a:1024155925106.
Inflammation has been reported to play an important role in cardiac surgery under cardiopulmonary bypass due to systemic endotoxemia. In order to develop strategies against this injury in future we studied the combined effect of a number of inflammatory mediators in myocardial ischemia/reperfusion. Coronary sinus blood samples of ten patients undergoing coronary artery bypass graft surgery (CABG) were obtained at three time intervals (1) before onset of bypass (2) 30 min after cross clamp, and (3) 10 min after removal of cross clamp. The samples were subjected to evaluate levels of nitric oxide byproducts (nitrite and nitrate and citrulline), inflammatory cytokines (interleukin-2, interferon-gamma and interleukin-6), adhesion molecules, (CD62L and CD54), ratio of cell surface markers (CD4/CD8 and TCRalphabeta/gammadelta) cell activation markers (CD69 and HLA DR) and second messengers (protein kinase C, inositol 1,4,5 triphosphate and intracellular calcium levels). Ischemia and further reperfusion resulted in significant rise in nitrite and nitrate levels (p < 0.001), interleukin-6 (p < 0.01), CD62L (p < 0.001), CD69 (p < 0.05), protein kinase C (p < 0.001) and intracellular calcium (p < 0.001). A fall in CD4/CD8 ratio was observed on reperfusion. These changes during CABG show that ischemia/reperfusion leads to a release of an array of pro-inflammatory mediators of tissue injury, which could lead to pathophysiological changes. Hence the study suggests the need of some protective therapies against these inflammatory markers.
据报道,由于全身内毒素血症,炎症在体外循环心脏手术中起重要作用。为了在未来制定针对这种损伤的策略,我们研究了多种炎症介质在心肌缺血/再灌注中的联合作用。在三个时间点采集了10例接受冠状动脉旁路移植术(CABG)患者的冠状窦血样:(1)体外循环开始前;(2)阻断钳夹30分钟后;(3)移除阻断钳夹10分钟后。对样本进行评估,检测一氧化氮副产物(亚硝酸盐、硝酸盐和瓜氨酸)、炎症细胞因子(白细胞介素-2、干扰素-γ和白细胞介素-6)、黏附分子(CD62L和CD54)、细胞表面标志物比值(CD4/CD8和TCRαβ/γδ)、细胞活化标志物(CD69和HLA DR)以及第二信使(蛋白激酶C、肌醇1,4,5-三磷酸和细胞内钙水平)。缺血及进一步再灌注导致亚硝酸盐和硝酸盐水平(p<0.001)、白细胞介素-6(p<0.01)、CD62L(p<0.001)、CD69(p<0.05)、蛋白激酶C(p<0.001)和细胞内钙(p<0.001)显著升高。再灌注时观察到CD4/CD8比值下降。CABG期间的这些变化表明,缺血/再灌注导致一系列组织损伤促炎介质的释放,这可能导致病理生理变化。因此,该研究表明需要针对这些炎症标志物采取一些保护性治疗措施。