Cell adhesion molecule mediation of myocardial inflammatory responses associated with ventricular pacing

Abstract

Poorly synchronized activation of the ventricles can lead to impairment of normal cardiac structure/function. We reported previously that short term (4 h) left ventricular (LV) pacing-induced ventricular dyskinesis led to an inflammatory response localized to the epicardium. Results from this study demonstrated that neutrophils may play a major role in this inflammatory process. Neutrophil recruitment to a site of injury is a process that is highly dependent on an upregulation of cell adhesion molecules (CAM). The dependence of ventricular dysynchrony-induced inflammatory responses on CAM upregulation has not been explored. To gain further insight, we used a mouse model of LV pacing to evaluate the role of CAM in mediating the inflammatory response associated with ventricular dyskinesis. We first examined the effects of LV pacing in wild-type mice. Results demonstrate that 40 min of LV pacing increases ICAM-1 immunostaining as well as myeloperoxidase activity and tissue oxidative stress by twofold in early-activated myocardium. Matrix metalloproteinase-9 activity also increased in the same region by ∼3.5-fold. To determine the role of CAM, mice null for ICAM-1 or p-selectin were subjected to 40 min LV pacing. Results demonstrate that the inflammatory response seen in the wild-type mice was significantly mitigated in the ICAM-1 and p-selectin null mice. In conclusion, results demonstrate that CAM expression plays a critical role in the triggering of LV pacing-induced inflammation, thus providing evidence of a vascular mechanism underlying this response. The mechanisms that trigger an upregulation of myocardial CAM expression and, therefore, inflammation await further investigation since they suggest a specific involvement of vascular events.