Analyzing Mitochondrial Oxidative Capacity and Efficiency in Human Heart Tissue

DATE: JUNE 2019
The Ohio State University | Physiology and Cell Biology
Mohammed Mashali, Post Doctoral Researcher

Hamilton Gastight syringes will be used during the high-resolution respirometry (HRR) using an oxygraph from Oroboros (Oroboros Instruments Corp, Innsbruck, Austria) to add the different components (mitochondria or cells, substrates, activator, and inhibitors) to the chambers of the oxygraph.

Hamilton syringes will be used as an associated tool to the oxygraph for measurement of ex-vivo mitochondrial oxygen consumption in the presence of specific substrates as a method for analyzing mitochondrial oxidative capacity and efficiency in fresh human heart tissue samples (Left ventricular and right ventricular free wall) obtained from patients diagnosed with end-stage heart failure and also from non-failing donors. Hamilton syringes will be one of the essential tools to perform our research plans. We plan to include this technique to be one of our basic lab protocols, hence, all the undergraduate students (3) and postgraduate students (3) in addition to the rotating students at our lab will be involved in learning and performing the high-resolution respirometry (HRR).

On regular basis, our lab receives non-failing human hearts in collaboration with the Life Line of Ohio Organ Procurement (LOOP) program from organ donors with no history of heart failure as well as failing human hearts from patients diagnosed with end-stage heart failure (either ischemic or non-ischemic) and undergoing cardiac transplantation. Basically, our lab is investigating the contractile force and kinetics of contraction and relaxation using left and right ventricular intact trabeculae isolated from those hearts (non-failing and end-stage failing) under near-physiological conditions. A gifted oxygraph has been recently received by our lab from our collaborators at University of Michigan to investigate the mitochondrial oxidative capacity and efficiency in specimens from these human hearts which may be essential for a better understanding of mitochondrial respiration in human heart failure pathophysiology. Although studies performed on heart tissue from animal models have provided important insights, but alterations in these models might not be directly applicable to mitochondrial changes that occur in chronic human heart failure, so using specimens from human hearts which are received by our lab would be advantageous to achieve these goals.

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