Investigation of cardiac metabolism using stable isotopes and mass spectrometry.
The technique described in this communication enables detailed investigations of cardiac metabolism using 13C-labeled substrates and mass spectrometric measurements of 13CO2 in the coronary effluent. To validate this technique for further studies isolated working rat hearts were perfused with 13C-labeled substrates in a bicarbonate-free perfusion fluid. The fraction of CO2 produced by oxidation of labeled substrate was calculated by the 13CO2/CO2 ratio in the coronary perfusate. The oxidation of 13C-acetate showed a linear correlation with 13C-acetate concentrations between 0.015 and 0.16 mmol/l. An inhibitor of acylcarnitine translocase, 2-(3-methylcinnamylhydrazono)-propionate (BM42.304) decreased CO2 production from 13C-palmitate from 48% +/- 4% to 31% +/- 3% (n = 11, SEM). Taking into account considerations of tracer kinetic theory rapidly accessible intracellular palmitate stores were estimated to be less than 900 nmol/g ww. This technique allows specific investigations of the oxidation of labeled substrates in the heart and may be useful for basic research and/or clinical diagnosis, thus avoiding the hazards of radiolabeled substrates.
Müller
F U
FU
Abteilung für experimentelle Kardiologie, Universität Göttingen, FRG.
Hunneman
D H
DH
Kahles
R
R
Hellige
G
G
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002247:Carbon Isotopes; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D002247:Carbon Isotopes; D005227:Fatty Acids; D010168:Palmitates; D002245:Carbon Dioxide