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Departments of 1Cardiology and 3Nuclear Medicine, Skejby Hospital, Aarhus University Hospital, and 2Department of Endocrinology and Metabolism, Aarhus Hospital, Aarhus University Hospital, Aarhus, Denmark
Submitted 14 February 2005 ; accepted in final form 25 March 2005
It is unknown whether short-term modulation of substrate supply affects cardiac performance in heart failure patients with chronic ischemic myocardium. The aim of this study was to determine whether modulation of myocardial substrate metabolism with insulin and free fatty acids (FFAs) affects contractile function of chronically stunned (CST) and hibernating (HIB) myocardium at rest and after maximal exercise. We studied eight nondiabetic patients with ejection fraction (EF) 30 ± 4% (SE) and CST/HIB in 49 ± 6% of the left ventricle: 36 ± 6% CST and 13 ± 2% HIB as determined by 99mTechnetium-Sestamibi single photon emission computed tomography (SPECT) and [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Each patient was subjected to a 3-h infusion of 1) saline, 2) insulin-glucose (i.e., euglycemic insulin clamp; high insulin, suppressed FFA), and 3) somatostatin-heparin (suppressed insulin, high FFA). Echocardiographic endpoints were global EF and regional contractile function [maximum velocity (Vmax) and strain rate (
max)] as determined by tissue Doppler imaging at steady state and after maximal exercise. 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 region. After maximal exercise, contractile function increased in control, CST, and HIB (P < 0.05), but not in infarct, regions. Exercise-induced contractile increments were unaffected by metabolic modulation. Metabolic modulation does not influence contractile function in CST and HIB regions. Chronic ischemic myocardium has preserved ability to adapt to extreme, short-term changes in substrate supply at rest and after maximal exercise.
glucose; hibernation; myocardial stunning
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