Abstract 10882: Acute Venous Congestion Induces Local Release of Proinflammatory Cytokines and Endothelial Activation in Humans
Background: Accumulating evidence suggests that venous congestion begins to occur weeks before symptoms worsen, requiring hospitalization for acute decompensated heart failure (ADHF). Whether congestion itself promotes progression to ADHF by causing inflammation and endothelial cell (EC) activation is unknown. We used a novel model of acute venous congestion coupled with blood testing and endothelial gene expression profiling to characterize cytokine and endothelial response to acute biomechanical stress.
Methods: 23 healthy subjects were studied. Venous arm pressure was increased to 30 mmHg above baseline level by inflating a blood pressure (BP) cuff around the non-dominant arm. Blood and endothelial cells (ECs) were sampled from test and control (lacking an inflated BP cuff) arm before and after 75 minutes of venous congestion using angiocatheters and endovascular wires. Magnetic beads coated with EC specific antibodies were used for EC separation; amplified mRNA was analyzed by Affymetrix HG-U133 2.0 Microarray.
Results: Experimental venous congestion did not influence BP, heart rate, arterial O2 saturation, venous lactic acid or glucose. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6) and vascular cell adhesion molecule 1 (VCAM-1) levels were significantly increased in the congested arm, but not in the control arm. 3,437 probe sets were differentially expressed in venous ECs before vs. after venous congestion (p<0.05), including ET-1 and VCAM-1.
Conclusions: Experimental venous congestion is sufficient i) to cause local release of proinflammatory cytokines, and ii) to activate venous ECs in humans. Our preliminary findings support the hypothesis that venous congestion might be a causal contributor (as opposed to a consequence) to the pathophysiology of ADHF via its influence on inflammation and endothelial activation.
- © 2011 by American Heart Association, Inc.