Abstract
IntroductionEndotoxemia and the systemic inflammatory response syndrome have a significant impact on post-surgery outcome, particularly in the elderly. The cytokine response to endotoxin is altered by aging. We tested the hypothesis that vulnerability to endotoxemic cardiac depression increases with aging due to age-related augmentation of myocardial inflammatory responses.MethodsAdult (4 to 6 months) and old (20 to 22 months) C57/BL6 mice were treated with endotoxin (0.5 mg/kg, iv). Left ventricle (LV) function was assessed using a microcatheter system. Chemokines and cytokines in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells in the myocardium were examined using immunofluorescence staining.ResultsOld mice displayed worse LV function (cardiac output: 3.0 ± 0.2 mL/min versus 4.4 ± 0.3 mL/min in adult mice) following endotoxin treatment. The exaggerated cardiac depression in old mice was associated with higher levels of monocyte chemoattractant protein-1 (MCP-1) and keratinocyte chemoattractant (KC) in plasma and myocardium, greater myocardial accumulation of mononuclear cells, and greater levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) in plasma and myocardium. Neutralization of MCP-1 resulted in greater reductions in myocardial mononuclear cell accumulation and cytokine production, and greater improvement in LV function in old mice while neutralization of KC had a minimal effect on LV function.ConclusionOld mice have enhanced inflammatory responses to endotoxemia that lead to exaggerated cardiac functional depression. MCP-1 promotes myocardial mononuclear cell accumulation and cardiodepressant cytokines production, and plays an important role in the endotoxemic cardiomyopathy in old mice. The findings suggest that special attention is needed to protect the heart in the elderly with endotoxemia.
Highlights
Endotoxemia and the systemic inflammatory response syndrome have a significant impact on post-surgery outcome, in the elderly
Heart rate increased in both adult and old mice treated with endotoxin in comparison to saline-treated controls (Table 1)
Endotoxemia causes a reduction in left ventricle (LV) function, and old mice have worse LV function during endotoxemia
Summary
Endotoxemia and the systemic inflammatory response syndrome have a significant impact on post-surgery outcome, in the elderly. It is well known that cardiac contractile dysfunction caused by bacterial endotoxin is associated with the production of pro-inflammatory mediators [1]. We and others have observed that endotoxin induces cardiac contractile depression through upregulation of myocardial production of pro-inflammatory cytokines, such as TNF-α and IL-1β [3,4,5,6]. Trauma and stress associated with major surgery can cause gut bacteria translocation, which leads to endotoxemia and the systemic inflammatory response [7,8]. The systemic inflammatory response associated with major surgery has a significant impact on the post-surgery outcome in the geriatric population [9,10]. Understanding of the mechanism that regulates the inflammatory responses in the aging heart is important for peri-surgical care in the elderly
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
