Ann Thorac Surg 2002;73:1910-1911
© 2002 The Society of Thoracic Surgeons
Original article: cardiovascular
Invited commentary
A. Leinsa,
J. Cremer, MD, PhDa
a Department of Cardiovascular Surgery, University of Kiel, Arnold-Hellerstr. 7, D-24105 Kiel, Germany
e-mail: aleins{at}kielheart.uni-kiel.de
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Introduction
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Cardiac surgery especially with the use of cardiopulmonary bypass (CPB) is associated with significant systemic inflammatory response. One manifestation of systemic inflammatory response with excessive pro-inflammatory cytokine expression is lactic acidosis [1, 2]. Hyperlactatemia is a hallmark of severe circulatory failure or shock and is correlated with outcome in critical illness patients [3]. In these patients, lactic acidosis is mainly related to an elevated lactate production, whereas alterations in lactate utilization due to hypoxic liver damage is negligible [4].
There is evidence for a direct effect of TNF and interleukines (ILs) on lactic acid production and lactic homeostasis. The proinflammatory TNF-
may directly increase lactic acid production by inhibiting pyrovate dehydrogenase activity [5, 6]. Interleukin-10 (IL-10) is known as a pluripotent anti-inflammatory cytokine that inhibits TNF- synthesis, and antagonizes its actions by upregulation of cytokine antagonists [7]. Recently published data report a significant influence of genetic factors on the production of ILs or TNF as well as on the modulation of systemic inflammatory response [8, 9].
The study of Ryan and associates is the first to analyze the correlation between lactic acid levels and the presence of allelic polymorphisms (TNFB, TNF G-308A and IL-10 G-1082A, IL-1ß +3953, IL-6 -174, IL-10 -592) in critically ill patients after CPB. Using well-known polymerase chain reaction based techniques, Ryan identified a genotype highly associated with lactic acidosis. Yet, there were only four patients homozygous for TNFB1 and IL-10 G-1082A allele out of a group of 21 study and 30 control patients. In these identified patients, the TNFB1 allele was associated with elevated pro-inflammatory TNF-ß expression and IL-10 G-1082 allele induced reduction of anti-inflammatory IL-10 production with subsequent excessive lactic acid production, as typically seen in patients with SIRS. Thereby, lactic acidosis is traditionally attributed to anaerobic glycolysis and regarded as an unreliable indicator of tissue hypoxia. Likewise, hyperlactatemia is observed in patients with hyperdynamic circulatory derangement after heart surgery [2]. The aetiology of SIRS after CPB is conceived as an interrelated process of pro- and anti-inflammatory cytokines. Ryan and associates elucidates one very interesting aspect of the complexity of this clinical syndrome: genetic alterations and predisposition for failure of the inflammatory response based on TNF and ILs allele polymorphisms.
Using the approach of Ryan and associates for identifying patients, who had a certain probability to develop increasing lactic acid levels, there were only four positive tests out of 51. Seventeen of the 51 patients became seriously ill without any detectable TNF/ILs-allele abnormalities. Our strongest interests in studies on SIRS after open heart operation focus on preoperative identification tools to detect patients who will likely develop SIRS and preventive treatment options to avoid SIRS. Ryan and associates describe one promising new approach to evaluate the individual preoperative risk of a patient using current laboratory techniques; however, further investigations are necessary to transfer these techniques into daily patient care. Until now, clinical trials designed to inhibit the inflammatory response during critical illness by neutralizing of TNF in sepsis reveal a small but significant reduction in mortality.
These are important steps towards a new idea for diagnosis and treatment of patients with systemic inflammatory response after open heart operation. Further research is required, however, to gain more essential information about useful tools for identifying genetically high risk patients, particular regulatory mechanisms, and specific therapeutic options that are closely related to the complexity of cytokine production and activity in SIRS patients.
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