Effects of (+)-octanoylcarnitine in intact myocardium
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Fatty acid metabolites (long-chain esters of CoA and carnitine) which collect in ischemic myocardium can form amphiphiles capable of disrupting subcellular performance. It is important to document the role of these amphiphiles in intact tissue. D-Octanoylcarnitine was chosen because of its previously described effects on inhibiting palmitoylcarnitine transferasc (PCT-II) inin vitro andin vivo liver preparations. This inhibition will shift tissue levels of CoA and carnitine intermediates and thus alter amphiphile levels. The compound's actions in cardiac muscle are unknown.
Dose response curves were developed in intact hearts to test the influence of D-octanoylcarnitine at pharmacological concentrations. Measurements were obtained in working, extracorporeally perfused, swine hearts. Drug was administered either systemically (IV) or via dircct intracoronary (IC) infusions into the left anterior descending coronary circulation. Excess fatty acids were provided to ensure adequate fatty acid substrate for oxidation. Coronary flow was controlled at aerobic levels. Systemic administration of D-octanoylcarnitine (0.8–6.8 mM) resulted in transient peripheral hypotension which caused correlative decreascs in14CO2 production from labeled palmitate. Infusion of D-octanoylcarnitine (0.5–3.9 mM) IC did not cause appreciable hypotension and was not associated with suppression of fatty acid oxidation. No build-up of carnitine esters was noted in treated hearts but acyl CoA levels were reduced (p<-0.002). This latter finding was modestly related to increasing dose schedule of the compound in the IC group. The lack of suppression in fatty acid oxidation argues against significant inhibition of PCT II and lessens the attractiveness of using D-octanoylcarnitine in intact myocardium to selectively bloock fatty acid utilization at this locus.
Key wordsmyocardial metabolism fatty acid oxidation fatty acid blockers long-chain acyl esters
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- 1.Boyd W (1961) Regional pathology. Disceases of the heart. In: Textbook of Pathology. An Introduction to Medicine. Lea and Febiger, Philadelphia, pp 445–499Google Scholar
- 3.Delisle G, Fritz IB (1967) Interrelationships between hepatic fatty acid oxidation and gluconeogenesis: A possible regulatory role of carnitine palmityltransferase. Biochem 58:790–798Google Scholar
- 10.Liedtke AJ. Lipid burden in ischemic myocardium (submitted to J Mol Cell Cardiol)Google Scholar
- 11.May ME, Aftring RP, Buse MG (1980) Mechanism of the stimulation of branched chain oxoacid oxidation in liver by carnitine. J Biol Chem 255:2394–2397Google Scholar
- 14.McGarry JD, Foster DW (1974) Studies with (+)-octanoylcarnitine in experimental diabetic ketoacidosis. Diabetes 23:487–493Google Scholar
- 15.Molaparast-Saless F, Nellis SH, Liedtke AJ. The effects of propionylcarnitine taurine on cardiac performance in aerobic and ischemic myocardium (submitted to J Mol Cell Cardiol)Google Scholar
- 19.Rokitansky C (1854) A Manual of Pathological Anatomy. Vol. 4. Printed for the Sydenham Society. C and J Adland (Printers), London, pp 203–207Google Scholar
- 20.Snedecor GW, Cochran WG (1980) Statistical methods. Ames, Iowa, Iowa State University Press, pp 39–64, 334–362Google Scholar
- 24.Virchow R (1860) Cellular Pathology as Based Upon Physiological and Pathological Histology. P Blakiston, Son & Co. Philadelphia, pp 383–408Google Scholar