Year of Publication
Doctor of Philosophy (PhD)
Dr. Kenneth S. Campbell
The left ventricle of the heart relaxes when it fills with blood and contracts to eject blood into circulation to meet the body’s metabolic demands. Dysfunction in either relaxation or contraction of the left ventricle can lead to heart failure. Transmural heterogeneity is thought to contribute to normal ventricular wall motion but it is not well understood how transmural modifications affect the failing left ventricle. The overall hypothesis of this dissertation is that normal left ventricles exhibit transmural heterogeneity in cellular level contractile properties and with aging and heart failure there are region-specific changes in cellular level contractile mechanisms.
Age is the biggest risk factor associated with heart failure and therefore we investigated transmural changes in Ca2+ handling and contractile proteins in aging F344 rats before the onset of heart failure. We found that in 22-month old F344 rats there is a region-specific decrease in cardiac troponin I phosphorylation in the sub-epicardium that may contribute to slowed myocyte relaxation in the sub-epicardial cells of the same age.
We then investigated the transmural patterns of contractile properties in myocardial tissue samples from patients with heart failure. Force and power output reduced most significantly in the samples from the mid-myocardial region when compared to sub-epicardium and sub-endocardium of the failing hearts. There was a region-specific increase in fibrosis is the mid-myocardium of the failing hearts. Myocardial power output was correlated with key sarcomeric proteins including cardiac troponin I, desmin and myosin light chain-1.
The results in this dissertation reveal novel region-specific modifications in contractile properties in aging and heart failure. These transmural effects can potentially contribute to disruption in normal wall motion and lead to ventricular dysfunction.
Haynes, Premi, "TRANSMURAL HETEROGENEITY OF CELLULAR LEVEL CARDIAC CONTRACTILE PROPERTIES IN AGING AND HEART FAILURE" (2014). Theses and Dissertations--Physiology. 16.