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1 Aarhus University Hospital, Department of Cardiology, Aarhus, Denmark
2 Aarhus University Hospital, Department of Endocrinology and Metabolism, Aarhus, Denmark
3 Aarhus University Hospital, Department of Nuclear Medicine, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: henrikwiggers{at}dadlnet.dk.
OBJECTIVES: To study whether modulation of myocardial substrate metabolism with insulin and free fatty acids (FFA) affects contractile function of chronically stunned (CST) and hibernating myocardium (HIB) at rest and after maximal exercise.
BACKGROUND: It is unknown whether short-term modulation of substrate supply affects cardiac performance in heart failure patients with chronic ischemic myocardium.
METHODS: We studied 8 non-diabetic patients with EF 30%±4% (mean±SEM) and CST / HIB in 49%±6% of the left ventricle on 99mTechnetium-Sestamibi / 18F-flouro-deoxyglucose SPECT (36%±6% CST and 13%±2% HIB). Each patient received a 3-hour infusion of 1) isotonic saline, 2) euglycemic insulin clamping (high insulin, FFA suppressed), and 3) somatostatin and heparin (insulin suppressed, high FFA). Echocardiographic endpoints were global EF and regional contractile function by tissue Doppler (maximum velocity Vmax and strain rate 
max) at steady state and after maximal exercise.
RESULTS: EF was similar at baseline and steady state and increased after exercise to 36%±5% (P<0.05). Baseline regional Vmax and max were highest in control, intermediate in CST and HIB, and lowest in infarct regions (P<0.05). Steady state EF, Vmax and max were not affected by metabolic modulation in any type of region. After maximal exercise contractile function increased in control, CST, and HIB (P<0.05), but not in infarct regions. The exercise induced contractile increments were unaffected by metabolic modulation.
CONCLUSIONS: Metabolic modulation does not influence contractile function in CST and HIB. Chronic ischemic myocardium has preserved ability to adapt to extreme, short-term changes in substrate supply at rest and after maximal exercise.
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