Overcoming the Physiological Limitations of Ex Vivo Heart Preparations
Open AccessAs heart-related health conditions become more prevalent, it becomes increasingly important to study cardiac physiology in normal and diseased hearts. Human models are the most desirable for studying cardiac function, but are not always available. It is for this reason that the isolated perfused mammal heart, established in 1895 by Oskar Langendorff, remains a prominent tool for the study of ex vivo cardiac physiology. Isolated perfused hearts, in which the entire organ can be studied separately outside of the animal, are useful for research because they allow for precise control of variables, and they can be made readily available. Despite the long-standing history of isolated heart models and their critical role in understanding cardiac function, current models contain several shortcomings; these limitations must be fully understood in order to accurately examine heart function in both healthy and diseased states. The experimental evidence presented in this dissertation demonstrates that use of Krebs-Henseleit buffer, the traditional substitute for blood in ex vivo heart studies, results in oxygen limitations that set the stage for atypical cardiac function. Furthermore, technological limitations require that researchers mechanically silence contracting hearts to prevent motion artifact from stifling fluorescence signals when measuring electrical behavior. Studying electrophysiology in contracting hearts is vital for understanding arrhythmia formation, which could be affected by pathological conditions such reduced oxygen supply and altered sympathetic pathways that are responsible for the cardiac "fight or flight" response in stress situations. Existing methods place isolated heart studies in a context that is far-removed from natural physiology. The methods and data of this dissertation seek to improve current isolated heart techniques by 1) measuring the differences in oxygen demand between heart preparations (such as contracting versus non-contracting) 2) establishing a non-contact, optogenetic method for activating intrinsic sympathetic pathways, and 3) implementing an accurate and reliable method for optically mapping contracting hearts. Better models will improve experimental design and data interpretation. These improvements will ultimately pave the way for a better understanding of cardiac physiology and pathophysiology, which can in turn lead to enhanced treatments of cardiac disease.
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Wengrowski_gwu_0075A_12530.pdf | 2018-01-16 | Open Access |
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