Chest
Volume 112, Issue 3, September 1997, Pages 676-692
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Clinical Investigations: Surgery
Inflammatory Response to Cardiopulmonary Bypass: Mechanisms Involved and Possible Therapeutic Strategies

https://doi.org/10.1378/chest.112.3.676Get rights and content

Background

Recent study of the inflammatory reactions occurring during and after cardiopulmonary bypass (CPB) has improved our understanding of the involvement of the inflammatory cascade in perioperative injury. However, the exact mechanisms of this complex response remain to be fully determined.

Methods

Literature on the inflammatory response to CPB was reviewed to define current knowledge on the possible pathways and mediators involved, and to discuss recent developments of therapeutic interventions aimed at attenuating the inflammatory response to CPB.

Results

CPB has been shown to induce complement activation, endotoxin release, leukocyte activation, the expression of adhesion molecules, and the release of many inflammatory mediators including oxygen-free radicals, arachidonic acid metabolites, cytokines, platelet-activating factor, nitric oxide, and endothelins. Therapies aimed at interfering with the inflammatory response include the administration of pharmacologic agents such as corticosteroids, aprotinin, and antioxidants, as well as modification of techniques and equipment by the use of heparin-coated CPB circuits, intraoperative leukocyte depletion, and ultrafiltration.

Conclusions

Improved understanding of the inflammatory reactions to CPB can lead to improved patient outcome by enabling the development of novel therapies aimed at limiting this response.

Section snippets

Complement Activation

The complement system consists of some 20 plasma proteins and forms part of the body's defense mechanism. It is activated in a cascade sequence by the classic and the alternative pathways during CPB. The exposure of blood to extracorporeal circuits activates the alternative pathway, leading to the formation of C3a and C5a,4, 5 while reversal of heparin with protamine activates the classical pathway with an associated rise in C4a levels and further rise in C3a levels.6, 7, 8 Endotoxin release in

Pharmacologic Strategies

Steroid Pretreatment—Old Question, New Answers: Corticosteroids have been used during open heart surgery for >30 years.129 However, the mechanism of this intervention is still incompletely defined. Early studies focused on the hemodynamic effects of corticosteroids. A single IV bolus of a massive dose of corticosteroids has been suggested as a therapy for low output syndrome after CPB, due to the effects of vasodilatation with increased venous capacitance.130 In a large series of patients

The More We Learn, the More We Have to Learn

Much has been discovered regarding the inflammatory cascade and its initiation by CPB, but many of the complex interactions in this process remain elusive. The mechanisms of this extremely complicated network underly so many changes, including complement activation, endotoxin release, leukocyte activation, the expression of adhesion molecules, and the release of many endogenous substances including oxygen-free radicals, arachidonic acid metabolites, cytokines, PAF, NO, endothelins, and others.

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    This study was supported by Fondation pour la Chirurgie Cardiaque, Belgium.

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