A new experimental model for studies of drug actions on myocardial metabolism. Application to a study of the influence of POCA.
In order to study myocardial metabolism by external detection, quantitative information on the metabolism of a gamma-emitting iodinated fatty acid (IHA) was obtained from time-activity curves of radioactivity in different compartments. A 4-compartment mathematical model was then developed; compartments 0, 1, 2, and 3 correspond respectively to vascular IHA, intracellular IHA, esterified forms, and iodide resulting from mitochondrial oxidation of IHA. We applied this model to a study of the influence of an inhibitor of fatty acid oxidation, POCA (2-[5(4 chlorophenyl) pentyl]-oxirane-2-carboxylate). Isolated rat hearts were perfused for 20 min with Krebs liquid containing increasing concentrations of POCA. IHA was then injected as a bolus at the entrance of the coronary network. The level of cardiac radioactivity was recorded for 30 min and the division into the 4 compartments was simulated at different concentrations of POCA. The drug appeared to increase the myocardial retention of IHA and slow down the speed of degradation and storage; the variations were dose-dependent. These results correspond to those obtained by intracellular analysis. The proposed method, which is reliable and sensitive, is an interesting experiment for pharmacological studies of cardiac metabolism.
Bontemps
L
L
Laboratoire de Physiologie Animale, CNRS UA 632, Saint-Martin-d'Hères, France.
Demaison
L
L
Dubois
F
F
Pernin
C
C
Mathieu
J P
JP
Vidal
M
M
Comet
M
M
Cuchet
P
P
D000818:Animals; D004852:Epoxy Compounds / Q000378:metabolism* / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000378:metabolism* / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D010169:Palmitic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D007004:Hypoglycemic Agents; D007457:Iodine Radioisotopes; D010169:Palmitic Acids; C035111:B 807-27; C040272:16-iodohexadecanoic acid; C033891:ethyl 2-(5-(4-chlorophenyl)pentyl)oxiran-2-carboxylate