Competition between palmitate and ketone bodies as fuels for the heart: study with positron emission tomography.
To test the ability of ketone bodies to inhibit myocardial fatty acid oxidation in vivo, the myocardial clearance kinetics of [1-11C]palmitate was assessed with positron emission tomography in six fasted volunteers and six instrumented dogs, studied repeatedly before and during infusion of 3-hydroxybutyrate (17 mumol.kg-1 x min-1). With the use of multiexponential fitting of tissue time-activity curves, the size, half time (T1/2), and index of the early rapid phase of 11C myocardial clearance, reflecting palmitate oxidation, were calculated. In humans, the relative size (-28%, P < 0.001) and index (-37%, P < 0.01) of the early rapid phase decreased significantly during infusion of 3-hydroxybutyrate, consistent with decreased fatty acid oxidation. Paradoxically, T1/2 decreased from 10.1 +/- 1.6 to 7.4 +/- 1.1 min (P < 0.01). To elucidate possible mechanisms, multiple coronary arteriovenous samples were obtained from the dogs to assess the efflux of oxidized and nonmetabolized tracer. Infusion of 3-hydroxybutyrate resulted in decreased myocardial [11C]CO2 production (-40%, P < 0.05) and reduced palmitate retention (-38%, P < 0.05). In three dogs, the arteriovenous difference in radiolabeled palmitate became negative 10 min after injection, indicating backdiffusion of nonmetabolized tracer from the myocardium. Thus a steady-state infusion of 3-hydroxybutyrate, resulting in physiological plasma levels, alters [1-11C]palmitate kinetics in vivo by decreasing myocardial long-chain fatty acid oxidation and by increasing backdiffusion of nonmetabolized tracer.
Vanoverschelde
J L
JL
Department of Internal Medicine, University of Louvain, Brussels, Belgium.
Wijns
W
W
Kolanowski
J
J
Bol
A
A
Decoster
P M
PM
Michel
C
C
Cogneau
M
M
Heyndrickx
G R
GR
Essamri
B
B
Melin
J A
JA
D020155:3-Hydroxybutyric Acid; D000328:Adult; D000818:Animals; D001667:Binding, Competitive; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D004285:Dogs; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000097:blood / Q000494:pharmacology; D007657:Ketone Bodies / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D005227:Fatty Acids; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D010169:Palmitic Acids; D002245:Carbon Dioxide; D019308:Palmitic Acid; D020155:3-Hydroxybutyric Acid