Abstract
Free fatty acids are considered to be the major energy source for the myocardium. To investigate the metabolic fate of this substrate in humans, 24 subjects underwent coronary sinus and arterial catheterization. 13 subjects were healthy volunteers and 11 subjects had symptoms of ischemic heart disease. [1-14C]oleate or [1-14C]palmitate bound to albumin was infused at a constant rate of 25 microCi/h. Oxidation was determined by measuring the 14CO2 production. The data demonstrated that a high percentage (84 +/- 17%) of the palmitate and oleate extracted by the myocardium underwent rapid oxidation. A highly significant correlation was present between the arterial level and the amount oxidized (r = 0.82, P less than 0.001 for palmitate; r = 0.77, P less than 0.001 for oleate). The isotope extraction ratio was greater than the chemical extraction ratio. This difference of 6 +/- 2 nmol/ml of blood in the young normal subjects was significantly less than the 12 +/- 4 nmol/ml observed in the ischemic heart disease patients (P less than 0.001).
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- BALLARD F. B., DANFORTH W. H., NAEGLE S., BING R. J. Myocardial metabolism of fatty acids. J Clin Invest. 1960 May;39:717–723. doi: 10.1172/JCI104088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BARTHELMAI W., CZOK R. [Enzymatic determinations of glucose in the blood, cerebrospinal fluid and urine]. Klin Wochenschr. 1962 Jun 1;40:585–589. doi: 10.1007/BF01478633. [DOI] [PubMed] [Google Scholar]
- BING R. J., SIEGEL A., UNGAR I., GILBERT M. Metabolism of the human heart. II. Studies on fat, ketone and amino acid metabolism. Am J Med. 1954 Apr;16(4):504–515. doi: 10.1016/0002-9343(54)90365-4. [DOI] [PubMed] [Google Scholar]
- Braunwald E., Kloner R. A. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation. 1982 Dec;66(6):1146–1149. doi: 10.1161/01.cir.66.6.1146. [DOI] [PubMed] [Google Scholar]
- Bruce R. A., Hornsten T. R. Exercise stress testing in evaluation of patients with ischemic heart disease. Prog Cardiovasc Dis. 1969 Mar;11(5):371–390. doi: 10.1016/0033-0620(69)90027-9. [DOI] [PubMed] [Google Scholar]
- CARLSTEN A., HALLGREN B., JAGENBURG R., SVANBORG A., WERKO L. Myocardial metabolism of glucose, lactic acid, amino acids and fatty acids in healthy human individuals at rest and at different work loads. Scand J Clin Lab Invest. 1961;13:418–428. [PubMed] [Google Scholar]
- Cruickshank E. W., Kosterlitz H. W. The utilization of fat by the aglycaemic mammalian heart. J Physiol. 1941 Jan 14;99(2):208–223. doi: 10.1113/jphysiol.1941.sp003894. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dagenais G. R., Marquis Y., Gailis L. Assessment of myocardial free fatty acid metabolism in humans during heparin infusion. Recent Adv Stud Cardiac Struct Metab. 1975;10:3–16. [PubMed] [Google Scholar]
- EVANS J. R., OPIE L. H., SHIPP J. C. METABOLISM OF PALMITIC ACID IN PERFUSED RAT HEART. Am J Physiol. 1963 Oct;205:766–770. doi: 10.1152/ajplegacy.1963.205.4.766. [DOI] [PubMed] [Google Scholar]
- Fox K. A., Abendschein D. R., Ambos H. D., Sobel B. E., Bergmann S. R. Efflux of metabolized and nonmetabolized fatty acid from canine myocardium. Implications for quantifying myocardial metabolism tomographically. Circ Res. 1985 Aug;57(2):232–243. doi: 10.1161/01.res.57.2.232. [DOI] [PubMed] [Google Scholar]
- GOODALE W. T., HACKEL D. B. Myocardial carbohydrate metabolism in normal dogs, with effects of hyperglycemia and starvation. Circ Res. 1953 Nov;1(6):509–517. doi: 10.1161/01.res.1.6.509. [DOI] [PubMed] [Google Scholar]
- Garland P. B., Newsholme E. A., Randle P. J. Regulation of glucose uptake by muscle. 9. Effects of fatty acids and ketone bodies, and of alloxan-diabetes and starvation, on pyruvate metabolism and on lactate-pyruvate and L-glycerol 3-phosphate-dihydroxyacetone phosphate concentration ratios in rat heart and rat diaphragm muscles. Biochem J. 1964 Dec;93(3):665–678. doi: 10.1042/bj0930665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garland P. B., Randle P. J. Regulation of glucose uptake by muscles. 10. Effects of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, and of fatty acids, ketone bodies and pyruvate, on the glycerol output and concentrations of free fatty acids, long-chain fatty acyl-coenzyme A, glycerol phosphate and citrate-cycle intermediates in rat heart and diaphragm muscles. Biochem J. 1964 Dec;93(3):678–687. doi: 10.1042/bj0930678. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gertz E. W., Wisneski J. A., Neese R., Bristow J. D., Searle G. L., Hanlon J. T. Myocardial lactate metabolism: evidence of lactate release during net chemical extraction in man. Circulation. 1981 Jun;63(6):1273–1279. doi: 10.1161/01.cir.63.6.1273. [DOI] [PubMed] [Google Scholar]
- Gertz E. W., Wisneski J. A., Neese R., Houser A., Korte R., Bristow J. D. Myocardial lactate extraction: multi-determined metabolic function. Circulation. 1980 Feb;61(2):256–261. doi: 10.1161/01.cir.61.2.256. [DOI] [PubMed] [Google Scholar]
- Hagenfeldt L. A simplified procedure for the measurement of 14CO2 in blood. Clin Chim Acta. 1967 Nov;18(2):320–321. doi: 10.1016/0009-8981(67)90177-5. [DOI] [PubMed] [Google Scholar]
- Hance A. J., Robin E. D., Simon L. M., Alexander S., Herzenberg L. A., Theodore J. Regulation of glycolytic enzyme activity during chronic hypoxia by changes in rate-limiting enzyme content. Use of monoclonal antibodies to quantitate changes in pyruvate kinase content. J Clin Invest. 1980 Dec;66(6):1258–1264. doi: 10.1172/JCI109977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heyndrickx G. R., Millard R. W., McRitchie R. J., Maroko P. R., Vatner S. F. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest. 1975 Oct;56(4):978–985. doi: 10.1172/JCI108178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Julien P., Dagenais G. R., Gailis L., Roy P. E. Free fatty acid content of myocardial interstitial spaces of dog. Recent Adv Stud Cardiac Struct Metab. 1976 May 26;11:385–389. [PubMed] [Google Scholar]
- KENT S. P., DISEKER M. Early myocardial ischemia; study of histochemical changes in dogs. Lab Invest. 1955 Nov-Dec;4(6):398–405. [PubMed] [Google Scholar]
- Kaijser L. Effect of metabolic intervention on substrate metabolism in the human heart. Adv Myocardiol. 1980;2:51–59. [PubMed] [Google Scholar]
- Kjekshus J. K., Mjos O. D. Effect of free fatty acids on myocardial function and metabolism in the ischemic dog heart. J Clin Invest. 1972 Jul;51(7):1767–1776. doi: 10.1172/JCI106978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ko H., Royer M. E. A gas-liquid chromatographic assay for plasma free fatty acids. J Chromatogr. 1974 Jan 30;88(2):253–263. doi: 10.1016/s0021-9673(00)83149-0. [DOI] [PubMed] [Google Scholar]
- LaRosa J. C., Levy R. I., Brown W. V., Fredrickson D. S. Changes in high-density lipoprotein protein composition after heparin-induced lipolysis. Am J Physiol. 1971 Mar;220(3):785–791. doi: 10.1152/ajplegacy.1971.220.3.785. [DOI] [PubMed] [Google Scholar]
- Lassers B. W., Kaijser L., Carlson L. A. Myocardial lipid and carbohydrate metabolism in healthy, fasting men at rest: studies during continuous infusion of 3 H-palmitate. Eur J Clin Invest. 1972 Aug;2(5):348–358. doi: 10.1111/j.1365-2362.1972.tb00661.x. [DOI] [PubMed] [Google Scholar]
- Lassers B. W., Kaijser L., Wahlqvist M. L., Carlson L. A. Relationship in man between plasma free fatty acids and myocardial metabolism of carbohydrate substrates. Lancet. 1971 Aug 28;2(7722):448–450. doi: 10.1016/s0140-6736(71)92624-9. [DOI] [PubMed] [Google Scholar]
- Liedtke A. J. Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Prog Cardiovasc Dis. 1981 Mar-Apr;23(5):321–336. doi: 10.1016/0033-0620(81)90019-0. [DOI] [PubMed] [Google Scholar]
- MILLER H. I., GOLD M., SPITZER J. J. Removal and mobilization of individual free fatty acids in dogs. Am J Physiol. 1962 Feb;202:370–374. doi: 10.1152/ajplegacy.1962.202.2.370. [DOI] [PubMed] [Google Scholar]
- Mathey D. G., Chatterjee K., Tyberg J. V., Lekven J., Brundage B., Parmley W. W. Coronary sinus reflux. A source of error in the measurement of thermodilution coronary sinus flow. Circulation. 1978 Apr;57(4):778–786. doi: 10.1161/01.cir.57.4.778. [DOI] [PubMed] [Google Scholar]
- McDaniel H. G., Rogers W. J., Russell R. O., Jr, Rackley C. E. Improved myocardial contractility with glucose-insulin-potassium infusion during pacing in coronary artery disease. Am J Cardiol. 1985 Apr 1;55(8):932–936. doi: 10.1016/0002-9149(85)90720-9. [DOI] [PubMed] [Google Scholar]
- Miller H. I., Yum K. Y., Durham B. C. Myocardial free fatty acid in unanesthetized dogs at rest and during exercise. Am J Physiol. 1971 Mar;220(3):589–596. doi: 10.1152/ajplegacy.1971.220.3.589. [DOI] [PubMed] [Google Scholar]
- Mjos O. D., Kjekshus J. K., Lekven J. Importance of free fatty acids as a determinant of myocardial oxygen consumption and myocardial ischemic injury during norepinephrine infusion in dogs. J Clin Invest. 1974 May;53(5):1290–1299. doi: 10.1172/JCI107676. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Most A. S., Brachfeld N., Gorlin R., Wahren J. Free fatty acid metabolism of the human heart at rest. J Clin Invest. 1969 Jul;48(7):1177–1188. doi: 10.1172/JCI106082. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mueller H. S., Ayres S. M. Metabolic response of the heart in acute myocardial infarction in man. Am J Cardiol. 1978 Sep;42(3):363–371. doi: 10.1016/0002-9149(78)90929-3. [DOI] [PubMed] [Google Scholar]
- Muir J. R. The regional production of lipoprotein lipase in man. Clin Sci. 1968 Apr;34(2):261–270. [PubMed] [Google Scholar]
- Neely J. R., Rovetto M. J., Oram J. F. Myocardial utilization of carbohydrate and lipids. Prog Cardiovasc Dis. 1972 Nov-Dec;15(3):289–329. doi: 10.1016/0033-0620(72)90029-1. [DOI] [PubMed] [Google Scholar]
- Opie L. H. Metabolism of free fatty acids, glucose and catecholamines in acute myocardial infarction. Relation to myocardial ischemia and infarct size. Am J Cardiol. 1975 Dec;36(7):938–953. doi: 10.1016/0002-9149(75)90086-7. [DOI] [PubMed] [Google Scholar]
- RANDLE P. J., GARLAND P. B., HALES C. N., NEWSHOLME E. A. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785–789. doi: 10.1016/s0140-6736(63)91500-9. [DOI] [PubMed] [Google Scholar]
- ROTHLIN M. E., BING R. J. Extraction and release of individual free fatty acids by the heart and fat depots. J Clin Invest. 1961 Aug;40:1380–1386. doi: 10.1172/JCI104369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Randle P. J., Newsholme E. A., Garland P. B. Regulation of glucose uptake by muscle. 8. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles. Biochem J. 1964 Dec;93(3):652–665. doi: 10.1042/bj0930652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogers W. J., Russell R. O., Jr, McDaniel H. G., Rackley C. E. Acute effects of glucose-insulin-potassium infusion on myocardial substrates, coronary blood flow and oxygen consumption in man. Am J Cardiol. 1977 Sep;40(3):421–428. doi: 10.1016/0002-9149(77)90166-7. [DOI] [PubMed] [Google Scholar]
- Roy P. E. Lipid droplets in the heart interstitium: concentration and distribution. Recent Adv Stud Cardiac Struct Metab. 1975;10:17–27. [PubMed] [Google Scholar]
- Scheuer J., Brachfeld N. Myocardial uptake and fractional distribution of palmitate-1 C14 by the ischemic dog heart. Metabolism. 1966 Oct;15(10):945–954. doi: 10.1016/0026-0495(66)90165-x. [DOI] [PubMed] [Google Scholar]
- Schwaiger M., Schelbert H. R., Keen R., Vinten-Johansen J., Hansen H., Selin C., Barrio J., Huang S. C., Phelps M. E. Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium. J Am Coll Cardiol. 1985 Aug;6(2):311–320. doi: 10.1016/s0735-1097(85)80166-2. [DOI] [PubMed] [Google Scholar]
- Sheffield L. T., Roitman D. Stress testing methodology. Prog Cardiovasc Dis. 1976 Jul-Aug;19(1):33–49. doi: 10.1016/0033-0620(76)90007-4. [DOI] [PubMed] [Google Scholar]
- Simonsen S., Kjekshus J. K. The effect of free fatty acids on myocardial oxygen consumption during atrial pacing and catecholamine infusion in man. Circulation. 1978 Sep;58(3 Pt 1):484–491. doi: 10.1161/01.cir.58.3.484. [DOI] [PubMed] [Google Scholar]
- Ter-Pogossian M. M., Klein M. S., Markham J., Roberts R., Sobel B. E. Regional assessment of myocardial metabolic integrity in vivo by positron-emission tomography with 11C-labeled palmitate. Circulation. 1980 Feb;61(2):242–255. doi: 10.1161/01.cir.61.2.242. [DOI] [PubMed] [Google Scholar]
- Wisneski J. A., Gertz E. W., Neese R. A., Gruenke L. D., Morris D. L., Craig J. C. Metabolic fate of extracted glucose in normal human myocardium. J Clin Invest. 1985 Nov;76(5):1819–1827. doi: 10.1172/JCI112174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wisneski J. A., Gertz E. W., Neese R., Soo W. J., Bristow J. D., Adams J. R., Beaudry J. P. Myocardial metabolic alterations after contrast angiography. Am J Cardiol. 1982 Aug;50(2):239–245. doi: 10.1016/0002-9149(82)90172-2. [DOI] [PubMed] [Google Scholar]