Cytokine Responses to Cardiopulmonary Bypass: Lessons Learned From Cardiac Transplantation

doi:10.1016/S0003-4975(96)00931-9

The Annals of Thoracic Surgery

Volume 63, Issue 1, January 1997, Pages 269-276

https://doi.org/10.1016/S0003-4975(96)00931-9 Get rights and content

Abstract

Background. A growing body of evidence relates the release during cardiopulmonary bypass (CPB) of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-6, and IL-8, to the postoperative systemic inflammatory response syndrome. Antiinflammatory cytokines, such as IL-10, however, may also play an important role in limiting these complications.

Methods. The English-language literature was reviewed. Emphasis was placed on cytokine responses during clinical CPB for cardiac operations and, in particular, for heart and heart-lung transplantation.

Results. The recent data indicate that (1) although cytokine release can be triggered by many factors during CPB, ischemia-reperfusion may play the most important role; (2) the levels of tumor necrosis factor-α, IL-6, and IL-8 are correlated with the duration of cardiac ischemia and the myocardium is a major source of these three cytokines during CPB; (3) IL-10 levels are correlated with the duration of CPB and the liver is a major source of IL-10 during CPB; and (4) steroid pretreatment is an effective intervention to inhibit the release of proinflammatory cytokines and enhance IL-10 production.

Conclusions. The improved knowledge of cytokine responses to CPB may help to develop interventions aimed at reducing postoperative morbidity and mortality.

(Ann Thorac Surg 1997;63:269–76)

Section snippets

The Role of Endotoxin Release

Cardiopulmonary bypass can trigger the release of endotoxin [6, 27, 28, 29, 30], which can act as a powerful trigger for release of cytokines such as TNF-α [6, 30, 31]. Circulating endotoxin can appear immediately after the beginning of CPB [[27]] and the gut is its most likely source, as CPB has been shown to impair gut barrier function and lead to increase gut permeability [32, 33]. Although endotoxin is a potent trigger of the inflammatory cascade of mediators, the role of endotoxin in the

The Role of Complement Activation

Complement activation during CPB has also been suggested as contributing to the release of cytokines [9, 10, 11]. Complement is activated during CPB by blood–air interfaces or blood–material interaction and formation of heparin–protamine complexes, through either the alternate pathway (after the onset of CPB) or the classic pathway (after the administration of protamine). The degree of complement activation depends on the degree of surgical trauma and the duration of CPB [2, 3]. Ivey and

The Role of Ischemia-Reperfusion and the Relationship With Myocardial Injury

Most cases of CPB are associated with aortic cross-clamping, which results in global myocardial ischemia, whereas the release of the aortic cross-clamp results in myocardial reperfusion. Lindal and colleagues [[38]] recently showed in patients undergoing CPB that ischemia is associated with ultrastructural evidence of myocytic and microvascular injury, which seems to be reversible in nature, but subsequent reperfusion leads to more severe myocardial damage. Colletti and co-workers [[39]]

The Role of Interleukin-10 and the Organ Source of Cytokines

The observation of a release of IL-10 during CPB is interesting. Interleukin-10 is known to either directly inhibit the release of proinflammatory cytokines [42, 43], or indirectly exert antiinflammatory effects by triggering the release of IL-1 receptor antagonist and TNF soluble receptors 1 and 2 [[44]]. However, the production of IL-10 may also be enhanced by proinflammatory cytokines such as TNF-α [[45]]. We could not find any obvious relation between the levels of IL-10 and the other

The Importance of Temperature

The importance of temperature on the degree of mediator release during CPB has been addressed in several studies. Hypothermic (28° to 30°C) conditions have been shown to be associated with a lower cytokine release [[13]]. Lichtenstein and associates [[51]] reported that warm aerobic arrest of the heart is safe and effective even in high-risk patients with aortic cross-clamping time longer than 3 hours, and these patients were easily weaned from CPB without inotropic support. However, a

Anticytokine Strategies During Cardiopulmonary Bypass

At least some of the anticytokine strategies developed in the sepsis syndrome [[54]] may also be considered under CPB conditions, with the aim to reduce postoperative complications. Millar and associates [[55]] noted that removal of TNF-α and IL-6 by hemofiltration may have beneficial effects in children undergoing CPB. Steinberg and colleagues [[56]] found that heparin bonding of the bypass circuits can reduce the release of IL-6 and IL-8, but another Steinberg and associates [[9]] reported

Steroid Administration Before Cardiopulmonary Bypass

Corticosteroids have been administered in cardiac operations for many years [61, 62], but their exact mechanism of action has not been well defined. Steroid administration before CPB has been found to reduce complement activation [29, 63], although this effect has not always been observed [[12]]. Steroids may also prevent cytokine release. Jansen and colleagues [[12]] reported that steroid administration before CPB can effectively reduce TNF-α production after reperfusion. These effects were

Summary

The release of proinflammatory cytokines during and after CPB may play an important role in the deleterious effects of CPB to the heart and other organs. The mechanisms are primarily related to ischemia-reperfusion of the myocardium and also other organs, including the lung, the gut, and the liver. The production of proinflammatory cytokines is correlated with the duration of cardiac ischemia, as the myocardium is a main source of these cytokines during CPB. The production of antiinflammatory

Acknowledgements

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

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