J Thorac Cardiovasc Surg 2004;127:305
© 2004 The American Association for Thoracic Surgery
Endotoxemia and cardiac function
Christof Stamm, MD
Department of Cardiac Surgery, University of Rostock, Rostock, Germany
Douglas B. Cowan, PhD
Department of Anaesthesia, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
To the Editor:
We read with interest the article by Aydin and colleagues1 describing the degree of endotoxemia in patients undergoing on-pump versus off-pump coronary artery bypass grafting. The authors discussed the possible sources of endotoxin (lipopolysaccharide) during surgery, yet the effects of endotoxemia on cardiac function were mentioned only briefly.
Despite the similarity in outcomes between patients who underwent cardiopulmonary bypass and those who did not, we would like to point out that whereas endotoxemia is usually thought to increase cardiac output as a result of decreased systemic vascular resistance, it may actually have a significant negative inotropic effect. In cardiac surgical patients the combination of ischemia-reperfusion injury and myocardial endotoxin-mediated stress probably has a potent effect on myocardial function. The most commonly cited mechanism for this involves vascular as well as myocardial nitric oxide synthesis and takes several hours to reach functional relevance by disturbing intracellular calcium regulation and blunting contractile protein calcium sensitivity.2
Recently, we described an alternative mechanism that brings about lipopolysaccharide-induced negative inotropy within minutes. Cardiomyocytes were found to rapidly incorporate endotoxin, which activated the sphingomyelin-sphingosine signaling cascade through the release of tumor necrosis factor 
and direct, paracrine membrane receptor activation.3,4 Sphingosine directly inhibits calcium release from the sarcoplasmic reticulum, thereby reducing the amplitude of the calcium ionic transient and impairing systolic force generation. It is important to note that all the necessary signaling steps for cytokine-mediated negative inotropy in response to endotoxin stress can occur within the myocardium, without involvement of circulating cytokines. Studies that compare the inflammatory response to off-pump and on-pump surgery by measuring cytokine concentrations in blood often provide conflicting results, and the discrepancy between cytokine levels and outcome may be attributable to the lack of direct endotoxin measurements. The article by Aydin and colleagues1 fills that gap.
Cardiac index, as measured by Aydin and colleagues,1 is dependent on preload and afterload and therefore does not necessarily reflect the actual myocardial contractility. The increased lactate concentration, in part attributed to inhibition of pyruvate dehydrogenase, may also be interpreted as evidence for a compromised hemodynamic situation resulting from primarily impaired cardiac function. In this context, a more detailed, load-independent analysis of myocardial contractility might help to clarify the functional relevance of endotoxemia.
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References
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- Aydin NB, Gercekoglu H, Aksu B, Ozkul V, Sener T, Kiygil I, et al. Endotoxemia in coronary artery bypass surgery: a comparison of the off-pump technique and conventional cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2003;125:843–848[Abstract/Free Full Text]
- Luss H, Watkins SC, Freeswick PD, Imro AK, Nussler AK, Billiar TR, et al. Characterization of inducible nitric oxide synthase expression in endotoxemic rat cardiac myocytes in vivo and following cytokine exposure in vitro. J Mol Cell Cardiol. 1995;27:2015–2029[Medline]
- Cowan DB, Noria S, Stamm C, Garcia LM, Pouitas DN, del Nido PJ, et al. Lipopolysaccharide internalization activates endotoxin-dependent gene expression in cardiomyocytes. Circ Res. 2001;88:491–498[Abstract/Free Full Text]
- Stamm C, Cowan DB, Friehs I, Noria S, del Nido PJ, McGowan FX. Rapid endotoxin-induced alterations in myocardial calcium handling: obligatory role of cardiac TNF-. Anesthesiology. 2001;95:1396–1405[Medline]
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