We use cookies to personalise content and ads, to provide social media features and to analyse our traffic. Read more…

Myocardial energy transduction from substrates to mechanical wor


Get Directions

#var:page_name# cover

Speaker: Dan Beard, PhD Host: Bonnie Dougherty & Jason Papin, PhD
MR5, Room 3005

Affiliation: Professor, Department of Molecular and Integrative Physiology, Department of Medicine, Depart-ment of Biomedical Engineering, Department of Emergency Medicine Carl J. Wiggers Collegiate Professor of Cardiovascular Physiology

The energetic status of the myocardium is compromised in decompensated hypertrophy in the failing heart, with the chemical energy (in the form of the ATP hydrolysis potential) available for the heart to do work diminished compared to normal. Using multi-scale computer models to interpret data from humans and animal models of cardiac decompensation and heart failure, we have developed two novel hypotheses to guide our investigations of how the biochemical/metabolic state of the heart in heart failure affects the mechanical pumping of the heart: (1.) Diminished cytosolic ATP and increased inorganic phosphate (associated with impaired energy metabolism and depletion of cytoplasmic adenine nucleotides) impairs the mechanical function of the heart; and (2.) By blocking purine degradation pathways that may be overactive in the chronically stressed and/or periodically ischemic myocardium, we can increase/restore the nucleotide pool and protect the heart against mechanical dysfunction and failure. Testing these hypotheses using a combination of genetic and surgical models, and computer models, our studies point to the potential promise of whole new classes of pharmacological targets associated with purine nucleotide dephosphorylation, deamination, degradation, and transport.