title: Ventricular pacing-induced loss of contractile function and development of epicardial inflammation.
abstract: Perturbations in the normal sequence of ventricular activation can create regions of early and late activation, leading to dysynchronous contraction and areas of dyskinesis. Dyskinesis occurs across the left ventricular (LV) wall, and its presence may have important consequences on cardiac structure and function in normal and failing hearts. Acutely, dyskinesis can trigger inflammation and, in the long term (6 wk and above), leads to LV remodeling. The mechanisms that trigger these changes are unknown. To gain further insight, we used a canine model to evaluate transumural changes in myocardial function and inflammation induced by epicardial LV pacing. The results indicate that 4 h of LV suprathreshold pacing resulted in a 30% local loss of endocardial thickening. Assessment of neutrophil infiltration showed a significant approximately fivefold increase in myeloperoxidase activity in the epicardium versus the midwall/endocardium. Matrix metalloproteinase-9 activity increased ∼2 fold in the epicardium and ROS generation increased ∼2.5-fold compared with the midwall/endocardium. To determine the effects that electrical current alone has on these end points, a group of animals was subjected to subthreshold pacing. Significant increases were observed only in epicardial myeloperoxidase levels. Thus, the results indicate that transmural dyskinesis induced by suprathreshold epicardial LV activation triggers a localized epicardial inflammatory response, whereas subthreshold stimulation appears to solely induce the trapping of leucocytes. Suprathreshold pacing also induces a loss of endocardial function. These results may have important implications as to the nature of the mechanisms that trigger the inflammatory response and possibly long-term remodeling in the setting of dysynchrony.
authors.affiliation: Departments of 1Pharmacology, University of California-San Diego, La Jolla, 92093-0613, USA.
authors.forename: Katrina Go
authors.initials: KG
authors.lastname: Yamazaki
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Villarreal
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004285:Dogs; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009200:Myocardial Contraction / Q000502:physiology*; D020556:Neutrophil Infiltration / Q000502:physiology; D010493:Pericarditis / Q000201:enzymology*; D009195:Peroxidase / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9