Abstract 14585: Prognostic Significance of Left Ventricular Diastolic Function Associated with Inflammatory Response and Survival in Burn Patients
Purpose: Severe inflammation leads to cardiac diastolic dysfunction, an independent prognostic marker for mortality of critically ill patients. We investigated a possible molecular mechanism by which inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6]) cause left ventricular diastolic dysfunction in critically burned patients.
Methods: Critically burned patients admitted to the intensive care unit were enrolled. Diastolic function was evaluated using transthoracic echocardiography, and plasma levels of TNF-α and IL-6 were measured. Expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene in HL-1 cardiomyocytes was used as marker of diastolic heart failure. The effect of serum from burned patients on SERCA2 gene expression was investigated.
Results: Total burned surface area of patients was proportional to serum level of IL-6 and TNF-α (P < 0.001 for both). TNF-α and IL-6 serum levels were correlated with decelerating time, E/A, and E/Em (for TNF-α: r2 = 0.59, 0.45, and 0.52; respectively, and for IL-6: r2 = 0.63, 0.60, and 0.62, respectively; all P-values < 0.001). Significant improvement in diastolic function was associated with decreased cytokine levels (P < 0.001). Sera from critically burned patients down-regulated SERCA2 mRNA levels in HL-1 cardiomyocytes. There was a correlation between diastolic dysfunction and in-hospital mortality of critically burned patients (HR = 3.99, P = 0.038).
Conclusions: Inflammatory cytokines may cause cardiac diastolic dysfunction and increase mortality through down-regulation of SERCA2 gene expression. Novel therapeutic strategies that modulate inflammatory reactions may be useful in treating critically burned patients with cardiac diastolic dysfunction.
- © 2011 by American Heart Association, Inc.