Wuest 2013 Abstract IOC80

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Wuest RC (2013) Bioenergetics and mitochondrial dysfunction in chronic heart failure. Mitochondr Physiol Network 18.09.

Link: IOC80 Schroecken

Wuest RC (2013)

Event: MiPNet18.09 IOC80

In chronic heart failure, alterations occur in cardiac metabolism, enzyme content calcium handling and mitochondrial function. Mitochondrial dysfunction is a common observation in cardiac tissue in patients with left and right-ventricular heart failure, ischemic reperfusion injury, cardiac preconditioning, mechanical ventilation and type II diabetes. This suggest a general role for mitochondria in the cellular pathophysiology of these diseases. Despite the importance of mitochondria as regulators of energy supply, little is known on the processes in vivo that determine the activation of mitochondrial respiration in health and disease.

A photometry-based technique was used to simultaneously measure contractile function and autofluorescence of NADH (reduced nicotinamide adenine dinucleotide) and FAD (oxidized flavin adenine dinucleotide) in thin cardiac trabeculae. Three groups were studied: CH (monocrotaline: 40 mg.kg-1) or HF (60 mg.kg-1) and CON (saline). After 23±1 days, right ventricular trabeculae were excised, attached to a force transducer and superfused with oxygenated tyrode with 1 mM Ca2+. Autofluorescence of both NADH (excitation: 340 nm; emission: 470 nm) and FAD (450/525 nm) were recorded using an inverted microscope during transitions in pacing frequency between 0.5 and 1.2 or 3 Hz at 27 °C. Despite a smaller increase in force-time-integral, the initial changes in NADH and FAD were less pronounced in CH and HF than in CON, indicating a mismatch between dehydrogenase activity and mitochondrial respiration. These data reveal an altered mitochondrial complex function in CH and HF and further experiments with the Oroboros are planned to fully understand the changes in bio-energetic function in chronic heart failure.

Keywords: cardiomyocytes, diabetes, heart failure, ROS

O2k-Network Lab: NL Amsterdam Wuest RC


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Affiliation

Department of Physiology, VU University Medical Center, Amsterdam