Short‐term Changes in Left Ventricular Dyssynchrony Leads to Congestive Heart Failure

Ventricular dyssynchrony (VD) may lead to congestive heart failure (CHF). VD is characterized by a difference in the timing of contractions in the ventricles of the heart and has become a prominent pathophysiological feature of CHF. While studies have been done to understand the long‐term effects of VD that lead to CHF, little is known on the short‐term changes associated with VD. This study explores the acute effects of induced VD in‐vivo . Animals will undergo left ventricular pacing to induce VD and changes in mitochondrial structure and function will be analyzed to determine if abnormalities lead to apoptosis and cardiac remodeling. In this study, tissue homogenates from control and paced animals will be used to perform western blot analysis to investigate the changes in expression of mitochondrial respiratory chain complexes and proteins involved in apoptosis. We will measure adenosine triphosphate levels (ATP) to assess overall mitochondrial function. It is expected that VD increases cell death as a result of mitochondrial dysfunction, leading to activation of a fibrotic response. Immunohistochemistry will be used to investigate neutrophil infiltration and myofibroblast formation to confirm the activation of a fibrotic response. We will also evaluate reactive oxygen species and matrix metalloproteinases activities, which implicate cell injury and death that results in cardiac remodeling. We hypothesize that induced left ventricular pacing in a non‐congestive heart failure model will create short‐term changes that alter cardiovascular structure and metabolism. It is important to understand the short‐term physiological changes that result from dyssynchrony because electro‐mechanical conditions found in the absence of CHF can result in long‐term effects that may eventually lead to CHF. Support or Funding Information This research project will be supported through FATSA funding by Dr. Katrina Yamazaki. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .