The Influence of Lactate and Dipyridamole on Myocardial Fatty Acid Metabolism in Man, Traced with ¹²³l-17-lodo-heptadecanoic Acid^[*]

Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with ¹²³l-17-iodoheptadecanoic acid (¹²³l-17-HDA). In patients (paired, n = 7) lactate loading decreased the uptake of ¹²³l-17-HDA significantly from 27 (control: 22-36) to 20 counts/min/pixel (16-31; p <0.05 Wilcoxon). The half-time value increased to more than 60 rriin (n = 5), oxidation decreased from 61 to 42%. Coronary vasodilatation, a well-known side effect of lactate loading, was studied separately in a dipyridamole study (paired, n = 6). Coronary vasodilatation did not influence the parameters of the time-activity curve. These results suggest that changes in plasma lactate level as occurring, among other effects, during exercise will influence the parameters of dynamic ¹²³l-17-HDA scintigraphy of the heart.

Zusammenfassung

Nach intravenöser Applikation von jodmarkierter Fettsäure können Veränderungen im Myokardstoffwechsel durch externe Registrierung von Zeitaktivitätskurven festgestellt werden. In dieser szintigraphischen Studie wurde mittels ¹²³I-17-Jod-Heptadekansäure (¹²³J-17-HDA) der Einfluß des Laktats auf den Fettsäurestoffwechsel im gesunden menschlichen Myokard untersucht. Bei Patienten (n = 7) verringerte gleichzeitige Gabe von Laktat die myokardiale Aufnahme von ¹²³I-17-HDA signifikant von 27 (Streubreite 22-36) auf 20 Counts/ min/Pixel (16-31; p <0,05). Die Halbwertszeit stieg auf Werte über 60 min (n = 5), die relative Poolgröße der Oxidation verringerte sich von 61 auf 42%. Die koronare Gefäßerweiterung, eine bekannte Nebenwirkung der Laktat-Belastung, wurde in einer Dipyridamolstudie separat untersucht (n = 6). Die koronare Dilatation hatte keinen Einfluß auf die Parameter. Diese Ergebnisse legen nahe, daß bei Änderungen im Plasma-Laktatspiegel die myokardialen Parameter der dynamischen ¹²³I-17-HDA-Szintigraphie beeinflußt werden.

• REFERENCES

• 1 Altura B M, Altura B T. Interactions of locally produced humoral substances in regulation of the microcirculation. In: Van Houtte PM, Lensen I. eds. Mechanisms of vasodilation. New York: Karger; 1978: 98-106.
• 2 Bassingthwaighte J B, Caldwell J H, Martin G V. Regional flows and capillary permeability surfaces are proportionally heterogeneous in the dog heart. J Nucl Med 1989; 30: 798.
• 3 Bielefeld D R, Vary T C, Neely J R. Inhibition of carnitine palmitoyl-Co-A transferase activity and fatty acid oxidation by lactate and oxfenicine in cardiac musclc. J Mol Cell Cardiol 1985; 17: 619-25.
• 4 Boucher C A, Brewster D C, Darling R C. et al. Determination of cardiac risk by dipyridamole thallium imaging before peripheral vascular surgery. N Engl J Med 1985; 312: 389-94.
• 5 Bremer J, Osmundson H. Fatty acid oxidation and its regulation. In: Numa S. ed. Fatty acid oxidation and its regulation. Amsterdam - New York - Oxford: Elsevier; 1984: 113-54.
• 6 Bruce R, Blackmon J R, Jones J W, Strait G. Exercise testing in adult normal subjects and cardiac patients. Pediatrics 1963; 32: 742-56.
• 7 Cobb L A, Johnson W P. Hemodynamic relationship of anaerobic metabolism and plasma free fatty acids during prolonged strenuous exercise in trained and untrained subjects. J Clin Invest 1963; 42: 800-10.
• 8 Cuchet P, Demaison L, Bontemps L. et al. Do iodinated fatty acids undergo a nonspecific deiodination in the myocardium?. Eur J Nucl Med 1985; 10: 505-10.
• 9 Drake A J, Haines J R, Noble M I M. Preferential uptake of lactate by the normal myocardium in dogs. Cardiovasc Res 1980; 14: 65-72.
• 10 Dudczak R, Kletter K, Frischauf H. et al. The use of I-123-labeled heptadecanoic acid (HDA) as metabolic tracer: a preliminary report. Eur J Nucl Med 1984; 09: 81-5.
• 11 Duwel CMB, Visser F C, Eenige van M J, Den Hollander W, Roos J P. The fate of ¹²³I-17-iodoheptadecanoic acid during lactate loading: its oxidation is strongly inhibited in favor of its esterification. A radiochemical study in the canine heart. Nucl-Med 1990; 29: 24-7.
• 12 Duwel CMB, Visser F C, Eenige van M J, Roos J P. Variables of myocardial backdiffusion, determined with 17-iodo-heptadecanoic acid in the normal dog heart. Mol Cell Biochem 1989; 88: 191-4.
• 13 Duwel CMB, Visser F C, Eenige van M J, Roos J C, Roos J P. Pacing and the noninvasive evaluation of myocardial fatty acid metabolism by means of 17-¹²³I-heptadecanoic acid scintigraphy. Nucl-Med 1988; 27: 204-8.
• 14 Duwel CMB, Visser F C, Eenige van M J, Van der Lugt HAM, Roos J P. The influence of glucose on the myocardial time-activity curve during 17-iodo-123 heptadecanoic acid scintigraphy. Nucl Med Comm 1987; 08: 207-15.
• 15 Eenige van M J, Visser F C, Duwel C M B. et al. Analysis of myocardial time-activity curves of ¹²³I-heptadecanoic acid. I. Curve fitting. Nucl-Med 1987; 26: 241-7.
• 16 Eenige van M J, Visser F C, Karreman A J P. et al. Analysis of myocardial time-activity curves of ¹²³I-heptadecanoic acid. II. The acquisition time. Nucl-Med 1987; 26: 248-52.
• 17 Eenige van M J, Visser F C, Duwel C M B. et al. Comparison of 17-1-131 heptadecanoic acid kinetics from externally measured time-activity curves and from serial myocardial biopsies in an open-chcst caninc model. J Nucl Med 1988; 29: 1934-42.
• 18 Fixier D E, Watson J T, Wheeler J M, Willerson J T. Effect of hypertonic mannitol and isoproterenol on regional coronary flow following right ventriculotomy. Circulation 1976; 54: 26-31.
• 19 Freundlieb Ch, Höck A, Vyska K. et al. Myocardial imaging and metabolic studies with 17-123-iodoheptadecanoic acid. J Nucl Med 1980; 21: 1043-50.
• 20 Fridrich L, Gassner A, Sommer G. et al. Dynamic 123-I-HDA myocardial scintigraphy after aortocoronary bypass grafting. Eur J Nucl Med 1986; 12 (Suppl.): 24-6.
• 21 Höck A, Freundlieb Ch, Vyska K. et al. The influence of rehabilitation training on fatty acid metabolism in patients with myocardial infarction. In: Faivre G, Bertrand A, Cherrier F, Amor M, Neimann J L. eds. Noninvasive methods in ischemic heart disease. Nancy: Specia; 1982: 300-3.
• 22 Kloster G, Stöcklin G, Smith III E F, Schrör K. Omega-halofatty acids: a probe for mitochondrial membrane integrity. In vitro investigation in normal and ischemic myocardium. Eur J Nucl Med 1984; 09: 305-11.
• 23 Liedke A J. Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Prog Cardiovasc Dis 1981; 23: 321-36.
• 24 Liithy P, Chatelain P, Papageorgiou I, Schubiger A, Lerch R A. Assessment of myocardial metabolism with iodine-123 heptadecanoic acid: the effect of decreased fatty acid oxidation on deiodination. J Nucl Med 1988; 29: 1088-95.
• 25 Mulder C, Schouten J A, Popp-Snijders C. Determination of free fatty acids: a comparative study of the enzymatic versus the gas chromatographic and the colorimetric method. J Clin Chem Clin Biochem 1983; 21: 823-7.
• 26 Neely J R, Rovetto M J, Oram J F. Myocardial utilization of carbohydrates and lipids. Prog Cardiovasc Dis 1972; 15: 289-329.
• 27 Opie L H. Effects of regional ischemia on metabolism of glucose and fatty acids. Circ Res(Suppl 1) 1967; 38: 52-68.
• 28 Rabinovitch M A, Kalff V, Allen R. et al. co-123-I-hexadecanoic acid metabolic prove of cardiomyopathy. Eur J Nucl Med 1985; 10: 222-7.
• 29 Railton R, Rodger J C, Small D R, Harrower A D B. Myocardial scintigraphy with I-123 heptadecanoic acid as a test for coronary heart disease. Eur J Nucl Med 1987; 13: 63-6.
• 30 Reske S N, Schön S, Schmitt W. et al. Effect of myocardial perfusion and metabolic interventions on cardiac kinetics of phenylpentadecanoic acid (IPPA) 1-123. Eur J Nucl Med 1986; 12 (Suppl.): 27-31.
• 31 Rose C P, Goreski C A. Constraints on the uptake of labeled palmitate by the heart. Circ Res 1977; 41: 534-45.
• 32 Rosier H, Hess T, Weiss M. et al. Tomoscintigraphy assessment of myocardial metabolic heterogeneity. J Nucl Med 1983; 24: 285-96.
• 33 Schelbert H R, Henze E, Schön H R. et al. C-ll palmitate for the noninvasive evaluation of regional myocardial fatty acid metabolism with positron computed tomography. III. In vivo demonstration of the effects of substrate availability on myocardial metabolism. Am Heart J 1983; 105: 492-504.
• 34 Styles C B, Noujaim A A, Jugdutt B I, Sykes T R, Turner C. Omega iodo fatty acids scintigraphy - What are we measuring?. Eur Heart J 1985; 06 (Suppl B); 103-6.
• 35 Visser F C, Eenige van M J, Westera G. et al. Metabolic fate of radioiodinated heptadecanoic acid in the normal canine myocardium. Circulation 1985; 72: 565-71.
• 36 Visser F C, Eenige van M J, Duwel C M B, Roos J P. Radioiodinated free fatty acids: can we measure myocardial metabolism?. Eur J Nucl Med 1986; 12: 20-3.
• 37 Westera G, Wall van der E E, Visser F C. et al. The uptake of iodinated free fatty acids in the (ischemic) dog heart. Indications for a dual uptake mechanism. Int J Nucl Med Biol 1983; 10: 231-6.
• 38 Wall van der E E. Dynamic myocardial scintigraphy with ¹²³I-labeled free fatty acids. (Dissertation) Rodopi, Amsterdam: Free University; 1981
• 39 Wall van der E E, Heidendal G A K, Den Hollander W, Westera G, Roos J P. Metabolic imaging with 1-123 labeled heptadecanoic acid in patients with angina pectoris. Eur J Nucl Med 1981; 06: 391-6.
• 40 Wall van der E E, Westera G, Visser F C. et al. Influence of beta-adrenergic blockade on myocardial uptake of free fatty acids in experimental ischemia: an alternative role of beta blockade in the treatment of arrhythmias. In: Levi S, Gerard R. eds. Recent advances in cardiac arrhythmias I. London: John Libbey; 1983: 13-9.