title: Influence of insulin and free fatty acids on contractile function in patients with chronically stunned and hibernating myocardium.
abstract: 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 99m Technetium-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 (epsilon 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 epsilon max were highest in control, intermediate in CST and HIB, and lowest in infarct regions (P < 0.05). Steady-state EF, Vmax, and epsilon 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.
authors.affiliation: Department of Cardiology, Skejby Hospital, Aarhus Univ. Hospital, DK-8200 Aarhus N, Denmark. henrikwiggers@dadlnet.dk
authors.forename: Henrik
authors.initials: H
authors.lastname: Wiggers
authors.forename: Helene
authors.initials: H
authors.lastname: Nørrelund
authors.forename: Søren Steen
authors.initials: SS
authors.lastname: Nielsen
authors.forename: Niels H
authors.initials: NH
authors.lastname: Andersen
authors.forename: Jens Erik
authors.initials: JE
authors.lastname: Nielsen-Kudsk
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Torsten T
authors.initials: TT
authors.lastname: Nielsen
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002908:Chronic Disease; D002921:Cicatrix / Q000000981:diagnostic imaging / Q000209:etiology; D018592:Cross-Over Studies; D003971:Diastole; D004338:Drug Combinations; D004452:Echocardiography; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000000981:diagnostic imaging; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D017682:Myocardial Stunning / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D009638:Norepinephrine / Q000097:blood; D016037:Single-Blind Method; D013004:Somatostatin / Q000494:pharmacology; D014022:Tissue Survival; D015899:Tomography, Emission-Computed, Single-Photon; D016277:Ventricular Function, Left
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019344:Lactic Acid; D013004:Somatostatin; D006493:Heparin; D005947:Glucose; D009638:Norepinephrine