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Substrate Utilization by the Failing Human Heart by Direct Quantification Using Arterio-Venous Blood Sampling
Authors:Junichi Funada  Tim R. Betts  Leanne Hodson  Sandy M. Humphreys  Jon Timperley  Keith N. Frayn  Fredrik Karpe
Affiliation:1. The Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, United Kingdom.; 2. The Department of Cardiology, John Radcliffe Hospital, Oxford, United Kingdom.; 3. NIHR Oxford Biomedical Research Centre, Oxford Radcliffe Hospital Trust, Oxford, United Kingdom.;Innsbruck Medical University, Austria
Abstract:Metabolic substrate utilization of the human failing heart is an area of controversy. The purpose of this study is to directly quantify myocardial substrate utilization in moderately severe heart failure, type 2 diabetes and healthy controls using simultaneous coronary sinus and arterial blood sampling. Patients with heart failure (n = 9, mean NYHA 2.7±0.5), with type 2 diabetes (n = 5) and with normal heart function (n = 10) were studied after an overnight fast in connection with electrophysiological investigations/treatments.A systemic infusion of [2H2]palmitate allowed for the calculation of absolute palmitate extraction across the heart. Blood samples were analysed for non-esterified fatty acids, triacylglycerol, glycerol, glucose, pyruvate, lactate, 3-hydroxybutyrate, and blood gases after simultaneous sampling of arterial and coronary sinus blood. Arterio-coronary sinus metabolite concentration differences and fractional extractions for all substrates were similar between the groups. The absolute NEFA uptakes assessed by [2H2]palmitate extraction were also similar between the groups. Using direct measurements of metabolic substrate uptake by arterio-venous difference technique, the compensated human failing heart does not appear to have reduced myocardial fatty acid uptake.
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