Leukocyte activation during cardiopulmonary bypass: limitations of the inhibitory mechanisms and strategies.
Cardiopulmonary bypass, initiates a generalised response, which is primarily defensive in nature. This response is self regulated and terminated spontaneously. Obvious problems are complement and leucocyte activation, but several other cascades are also stimulated, which interact, accentuate or modulate this response. These supporting cascades include, release of inflammatory cytokines, an activation of kallikrein system, clotting and fibrinolytic mechanisms, and arachidonic acid metabolism. Because of an effective autoregulatory mechanism, only a small proportion of patients (<3%), undergoing cardiopulmonary bypass are adversely effected by this process. Prognosis of these patients is often unpredictable, but in general, high risk patients are likely to suffer most. A number of specific and non specific artificial measures have been introduced to control postperfusion problems, resulting from this process. These control measures are usually effective against a specific component of this generalised problem, and often fail to achieve desired effects. Efficacy of control measures is further limited by a continued activation of complement and leucocytes, via interactions between the mentioned inflammatory cascades. In view of these limitations, we have introduced certain modifications in our previously reported control strategy. These include an early identification of high risk and susceptible individuals and using specific inhibitors of complement activation for both initial and terminal stages.
Department of Cardiac Surgery, Baptist Medical Center, Birmingham, Alabama, USA.
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Fields
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D002462:Cell Membrane / Q000378:metabolism; D003167:Complement Activation; D003169:Complement Inactivator Proteins / Q000378:metabolism*; D006331:Heart Diseases / Q000097:blood* / Q000601:surgery; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D011183:Postoperative Complications / Q000097:blood / Q000517:prevention & control; D012307:Risk Factors
D015415:Biomarkers; D003169:Complement Inactivator Proteins