Energetics Studies of the Heart – from organ to tissue, to cell and molecules — The Association Specialists
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Energetics Studies of the Heart – from organ to tissue, to cell and molecules (380)

Hugh Paterson 1 , Mohammad Irhimeh 1 , Yu Suk Choi 1 2 , Imre Hunyor 3 , Metin Cicek 1 4 , Joanna Pakiraih 1 5 , James Mau 1 6 , Stephen Hunyor 1
  1. Cardiac Technology Centre, North Shore Heart Research Group, Kolling Institute, University of Sydney at Royal North Shore Hospitall, St Leonards, NSW, Australia
  2. Bioengineering, University of California, San Diego, La Jolla, California, USA
  3. Cardiology, Royal Prince Alfred Hospital, Sydney
  4. Applied Science, University of Muenster, Meunster, Germany
  5. Dept Radiology, Nationwide Childrens Hospital, Columbus, OH, USA
  6. Cardiology, RNSHospital, St Leonards, NSW

Background: The heart is exquisitely sensitive to substrate supply/demand for energetic tasks. A hierarchical Systems Response obscures defects until structure and function degenerate to clinical levels. Our models of pre-/clinical heart disease and highly sensitive analytical techniques should allow early determination of disturbed heart energetics.

Aims: To enhance skills for creation and assessment of various heart damage models in sheep to gain new insights into cause and effect relationships between global, tissue and cellular/mitochondrial response using new techniques/devices in a Systems Biology approach.

Methods: Creation of heart damage/disease models– regional and global using (i) coronary insufficiency/occlusion, overdrive pacing, (ii) altered myocardial stiffness induced by defined stiffness hydrogels. 

Global energetics using (a) LV Pressure-volume loops with conductance catheters during IVC occlusion to define load-independent contractility, (b) Pressure-volume area (PVA) determination of LV work, (c) LV Oxygen consumption directly measured by coronary artery (LMCA) flow probe and coronary A-V oxygen content. 

Local energetics. Micro-regions of damaged/normal myocardium are assessed by miniature high sensitivity (<0.1mm) sonomicrometer dimension sensing crystals and newly acquired Optronix counterpart pO2 and laser-Doppler perfusion monitoring for mechanical performance, blood flow, oxygen concentration and temperature.

Mitochondrial energetics will be assessed on biopsy specimens of myocardium in collaboration with expertise and skills in Kolling Institute’s Neuroscience laboratory.

Results: With varied severity of global and local heart damage or stress we will have vital information on heart muscle contractility and energetics, both global and local – using load-Independent techniques. Insights will be gained into cause and effect relationships between system/global, tissue and cellular mitochondrial disturbances resulting from the various interventions.

Conclusion: New and established models of varying degrees of human heart damage and disease, combined with novel probes and mitochondrial assays to measure global/local heart energetics will provide a Systems overview of the damage, repair/regeneration paradigm and effect of therapies.