Endothelial response to cardiopulmonary bypass surgery

Background. The vascular endothelium has been shown to actively participate in maintaining normal cardiovascular homeostasis by influencing the regula tion of membrane permeability, lipid transport, vasomotor tone, coagulation , fibrinolysis, and inflammation. Endothelial cells are very responsive to a wide range of local and systemic stimuli that occur during cardiopulmonar y bypass (CPB) operation. Major pathologic conditions result from impaired vascular function secondary to CPB, including vasospasm, coagulopathy, and widespread neutrophil adhesion secondary to a systemic inflammatory respons e. Additionally, more chronic responses to endothelial cell injury include the development of intimal hyperplasia and arteriosclerosis, both of which limit I-he long-term success of coronary artery bypass grafting. Methods. Because of the increasingly recognized role of the endothelium in the maintenance of normal cardiovascular function, this article will review the normal structure and function of the endothelium, as well as the major pathologic conditions that result in response to CPB. Results. Potential treatments to counteract endothelial cell dysfunction se condary to CPB are under active investigation. Strategies may be directed t oward blocking single cytokines, integrins, or adhesion molecules involved in endothelial dysfunction or, alternatively, toward targeting a molecular event that governs the expression of these proinflammatory, procoagulant, a nd vasoactive genes. In our laboratory, we have used both strategies to stu dy the pathologic response to CPB. We blocked neutrophil adhesion in subhum an primates with a monoclonal antibody. Alternatively, we targeted the tran scriptional activation of multiple genes involved in the endothelial cell's response to CPB. Conclusions. Although both therapies help elucidate the multiple, redundant pathways involved in the pathologic response to CPB, it is through molecul ar biology that we are beginning to understand the mechanics of transcripti onal control and translational expression that occurs in the endothelial ce ll in response to CPB. This knowledge will allow the development of therapi es that inhibit not a single cytokine or adhesion molecule, but rather an a rray of substances that result in the endothelial cell's pathologic respons e to CPB. (C) 1998 by The Society of Thoracic Surgeons.