Ryan King's Dissertation Defense (12/4/20): Effects of Perfusate Composition (Na+ and Ca2+) on Cardiac Electrical and Mechanical Function in the Isolated Langendorff-Perfused Heart
Graduate Student Dissertation Defense presented by the Fralin Biomedical Research Institute at VTC
About This Dissertation
In recent years, scientific rigor and reproducibility has garnered increased attention in both the scientific and public media. In several recent reports, the high attrition rate observed in clinical trials has been attributed to irreproducibility at the preclinical level. Preclinical cardiology is no exception to this rule. In King's systematic review of the ex vivo Langendorff-perfused heart, he found methods reporting to be sparse at best, specifically as it pertains to documenting the ex vivo perfusate compositions employed in the Langendorff heart. Previously, the Poelzing Lab, in which King conducts research, has demonstrated that variation in perfusate compositions can unmask disease states in genetically modified animals. In this dissertation, King exploits this concept with a therapeutic end-point in mind. The research shows that perfusate variation, specifically sodium and calcium elevations, can attenuate conduction slowing associated with severe hyperkalemia. Likewise, elevating sodium is capable of sustaining intrinsic rhythm where hearts would otherwise go asystolic. In doing so, elevated sodium prevents repolarization prolongation in these hearts. Together, these studies would suggest that elevating extracellular sodium, and calcium, should be considered as therapeutic targets in the context of conduction defects. However, when considering the heart’s primary role as a pump, King's research found that elevating sodium depresses cardiac mechanical function. This is both in a healthy and post-ischemic setting. In short, the dissertation shows that electrolyte variation may influence both cardiac electrophysiology and contraction; however, an improvement in one does not guarantee an improvement in both. Maintaining proper cardiac physiological function is a complex process that is tightly regulated by the ionic makeup of the extracellular environment and in order to improve insights from preclinical studies at the clinical level it is paramount that researchers properly document employed methodologies as they pertain to perfusate composition.
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Graduate Student, Translational Biology, Medicine and Health