Epicardial ventricular pacing induces a local inflammatory response in the outer layers of the left ventricle

Abstract

Abnormal heart wall motion as seen with dyssynchronous contraction of the left ventricle (LV) yields adverse chamber remodeling characterized by regions of wall thinning and hypertrophy. We hypothesized that heart wall abnormalities secondary to local epicardial ventricular pacing trigger local inflammation, reactive oxygen species (ROS) generation, matrix metalloproteinase (MMP) activation and fibrillar collagen degradation in the epicardial half of the LV wall. To examine this hypothesis we pursued LV pacing studies in anesthetized open‐chest dogs (n=5). Myeloperoxidase activity was significantly increased by 2.3 fold in the epicardial half (3±0.6 SEM, relative units=RU) of the LV compared to the endocardial half (1.3±0.2 RU). Our results also demonstrated a 2 fold increase in MMP‐9 activity in the epicardium (530±151 RU) compared to the endocardium (290±106 RU). In these same samples, ROS generation was increased by 2.2 fold (52±10 RU vs 24±7 RU). These results correlate with 3 fold more collagen damage in the epicardium (237±57 RU) when compared to the endocardium (78±22 RU). These results provide evidence that LV dyssynchrony can induce an inflammatory/injury response in the outer half of the LV wall, which may trigger localized remodeling. Supported by NIH HL‐43617.