Leukocyte Expression Analysis of the Systemic Inflammatory Response to Mechanical Circulatory Support Device Implantation

Introduction: The evolution of successful long-term mechanical circulatory support devices (MCSD) requires more accurate methods to evaluate risk-benefit ratios and predict outcomes. Multi-organ failure and sepsis account for almost 50% of early deaths. We hypothesized that, by characterizing the temporal dynamics of leukocyte expression profiles during MCSD-implantation, inflammatory signatures associated with adverse outcomes might ultimately be identified. Methods: Thirteen patients with end-stage heart failure requiring MCSD-implantation were enrolled in this study between March 2004 and February 2006. Routine blood draws were taken 24 h before implantation (Day 0), 24 h post-implantation (Day 1) and at Day 7. Peripheral blood mononuclear cells (PBMC) were isolated, and RNA was extracted and hybridized (Agilent Whole Human Genome CGH Microarray 44 K). Array data were analyzed using Gene Spring 9.0 software. Results: Our analysis showed significant differential expression across Day 0, 1 and 7 (ANOVA, p<.05, fold change>1.5) as shown in Figure 1.This result suggests an immediate Systemic Inflammatory Response response at Day 1 which trends back to baseline until Day 7.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Gene Set Enrichment Analysis (Subramaniam 2005) of our data against 1277 gene sets defined based on prior biological knowledge identified 54 genes sets positively significantly enriched at FDR<0.25 of which 61.1% were inflammatory sets, suggesting as expected a coordinated enrichment of inflammatory pathways within 24 h after MCSD-implantation. Conclusion Genome-wide leukocyte expression profiling suggests an overwhelming inflammatory pathway activation, providing an important first step in understanding Systemic Inflammatory Response to MCSD-implantation.