Pacing and the Non-Invasive Evaluation of Myocardial Fatty Acid Metabolism by Means of 17-¹²³I-Heptadecanoic Acid Scintigraphy

The extent of myocardial non-esterified fatty acid (NEFA) oxidation depends among other things on exogeneous NEFA supply and energy demand. In 6 patients with a multi-programmable pacemaker scintigraphy with 17-¹²³Iodo-heptadecanoic acid (17-¹²³I-HDA) was performed to investigate NEFA metabolism at two levels: at a control level (basal heart rate 69 ± 6) and at increased pace frequency (104 ± 5). In both situations the derived time-activity curves, measured during a period of 75 min, were fitted with a monoexponential plus a constant curve: A(t) = A(0).exp (-t ln2/T½) + C. The half-time value, the uptake measured as the peak activity and the relative size of the oxidation pool were determined. The median of the half-time value did not change: 24 min (range 19–31) in the control heart rate study and 22 min (19–27) during the increased pace frequency study. The median of the uptake increased significantly from 33 cpm/pixel/2 mCi/100 kg (23–34) to 40 cpm/ pixel/2 mCi/100 kg (35–42; p <0.05 Wilcoxon). The median of the relative size of the oxidation pool increased from 57% (52-62) to 69% (63–71; p <0.05). We conclude that during pacing the augmented need for NEFA resulted in a demonstrable increase in uptake and oxidation of 17-¹²³I-HDA. This result suggests that radioiodinated NEFA may be a valuable tool to quantify non-invasively the level of the myocardial NEFA metabolism in the human heart.

Zusammenfassung

Die Oxidation freier Fettsäuren (FFA) im Herzmuskel ist neben anderen Faktoren von der Menge exogen angebotener FFA und dem kardialen Energiebedarf abhängig. Bei 6 Patienten mit programmierbarem Schrittmacher wurde eine ¹²³J-Heptadekansäure-Szintigraphie durchgeführt, um den FFA-Stoffwechsel des Herzens unter Basalbedingungen (Herzfrequenz 69 ± 6) und bei schrittmacherinduzierter Tachykardie (Herzfrequenz 104 ± 5) durchgeführt. Bei beiden Untersuchungen wurden die erhaltenen kardialen Zeitaktivitätskurven mit einer monoexponentiellen Funktion und einer Konstante gefittet: A(t) = A(0) x Exp(-t x ln2/T½) + C. Es wurden die Halbwertszeit, der maximale Uptake und die relative Poolgröße der FFA-Oxidation ermittelt. Der Median der Halbwertszeit blieb unverändert: 24 min (Streubreite 19–31) unter Kontrollbedingungen und 22 min (19–27) während Frequenzstimulation. Der Median des Uptakes stieg signifikant von 33 cpm/Pixel/2 mCi/100 kg (23–34) auf 40 cpm/Pixel/2 mCi/ 100 kg (35–42; p <0,05; Wilcoxon-Test). Der Median der relativen Poolgröße des FFA-Oxidationspools nahm von 57% (52–62) auf 69% (63–71; p <0,05) zu. Wir folgern, daß während Frequenzstimulation der gesteigerte FFA-Bedarf zu einer nachweisbaren Zunahme von Uptake und Oxidation von ¹²³J-Heptadekansäure führt. Diese Ergebnisse weisen darauf hin, daß radiojodmarkierte freie Fettsäuren zur Untersuchung des Grades der FFA-Oxidation im menschlichen Herzen nützlich sein könnten.

• REFERENCES

• 1 Braunwald E, Ross Jr J, Sonnenblick E H. Mechanism of contraction of the normal and failing heart. Sec. Ed. Boston: Little Brown and Company; 1976
• 2 Bremer J, Osmundson H. Fatty acid oxidation and its regulation. In: Numa S. ed. Fatty acid metabolism and its regulation. Amsterdam - New York - Oxford: Elsevier Science Publishers; 1984. 05 113-54.
• 3 Cobb L A, Johnson W P. Hemodynamic relationship of anaerobic metabolism and plasma free fatty acids during prolonged strenuous exercise in trained and un-trained subjects. J Clin Invest 1963; 42: 800-10.
• 4 Crass III M F, McCaskill E S, Shipp J C. Effect of pressure development on glucose and palmitate metabolism in the perfused heart. Am J Physiol 1969; 216: 1569-76.
• 5 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.
• 6 Dubois F, Depresseux J C, Bontemps L. et al. Mathematical model of the metabolism of 123-I-16-iodo-9-hexadecanoic acid in an isolated rat heart. Eur J Nucl Med 1986; 11: 453-8.
• 7 Dudczak R. Myokardszintigraphie mit Jod-123-markierten Fettsäuren. Wien Klin Wschr 1983; 95 (Suppl. 143) 1-35.
• 8 Dudczak R, Kletter K, Frischauf H, Losert U, Angelberger P, Schmoliner R. The use of I-123-labeled heptadecanoic acid (HDA) as metabolic tracer: a preliminary report. Eur J Nucl Med 1984; 09: 81-5.
• 9 Duwel C M B, Visser F C, Eenige van M J, Lugt van der H A M. 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.
• 10 Eenige van M J, Visser F C, Duwel C M B. et al. Analysis of myocardial time-activity curves of I-123 heptadecanoic acid. Part 1: Curve fitting. Nucl-Med 1987; 26: 241-7.
• 11 Eenige van M J, Visser F C, Karreman A J P. et al. Analysis of myocardial time-activity curves of I-123 heptadecanoic acid. Part 2: The acquisition time. Nucl-Med 1987; 26: 248-52.
• 12 Feinendegen L F, Vyska K, Freundlieb C. et al. Non-invasive analysis of metabolic reactions in body tissues. The case of myocardial fatty acids. Eur J Nucl Med 1981; 06: 191-200.
• 13 Freundlieb C, Höck A, Vyska K. et al. Myocardial imaging and metabolic studies with 17-( 123-I) iodoheptadecanoic acid. J Nucl Med 1980; 21: 1043-50.
• 14 Gertz E W, Wisneski J A, Neese R, House A, Korte R, Bristow J D. Myocardial lactate extraction: multidetermined metabolic function. Circulation 1980; 61: 256-61.
• 15 Grover-McKay M, Schelbert H R, Schwaiger M. et al. Identification of impaired metabolic reserve by atrial pacing in patients with significant coronary artery stenosis. Circulation 1986; 74: 281-92.
• 16 Gibbs C L, Chapman J B. Cardiac energetics. In: Berne R M. ed. Handbook of Physiology, Section 2; The cardiovascular system, vol. 1: The heart. Baltimore-Maryland: Williams and Wilkins Co; 1979: 775-804.
• 17 Issekutz Jr B, Miller H I, Paul P, Rodahl K. Effect of lactic acid on free fatty acids and glucose oxidation in dogs. Am J Physiol 1965; 209: 1137-44.
• 18 Keul J, Doll E, Steim H, Fleer U, Reindell H. Über den Stoffwechsel des menschlichen Herzens. III. Der oxidative Stoffwechsel des menschlichen Herzens unter verschiedenen Arbeitsbedingungen. Pflüg Arch 1965; 282: 43-53.
• 19 Kloster G, Stöcklin G, Smith E F, Schrör K. Omegahalofatty acids: a probe for mitochondrial membrane integrity. In vitro investigations in normal and ischaemic myocardium. Eur J Nucl Med 1984; 09: 305-11.
• 20 Krebs R. Über die Beteiligung des basalen Sauerstoffverbrauches, der Aktivierung des Myokards sowie hämodynamischer Parameter am Gesamtsauerstoffverbrauch des Herzens. Klin Wschr 1970; 48: 767-76.
• 21 Margaria R, Cerretelli P, Aghemo P, Sassi G. Energy cost of running. J Appl Physiol 1963; 18: 367-70.
• 22 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.
• 23 Neely J R, Liebermeister H, Battersby E J, Morgan H E. Effekt of pressure development on oxygen consumption by isolated rat heart. Am J Physiol 1967; 212: 804-14.
• 24 Neely J R, Bowman R H, Morgan H E. Effect of ventricular pressure development and palmitate on glucose transport. Am J Physiol 1969; 216: 804-11.
• 25 Neely J R, Rovetto M J, Oram J R. Myocardial utilization of carbohydrate and lipids. Prog Cardiovasc Dis 1972; 15: 289-329.
• 26 Newsholme E A, Challis R A J, Crabtree B. Substrate cycles: their role in improving sensitivity in metabolic control. In: Ochs R S, Hanson R W, Hall J. eds. Metabolic regulation. Amsterdam - New York - Oxford: Elsevier Science Publishers; 1985: 102-6.
• 27 Opie L H. Effects of regional ischemia on metabolism of glucose and fatty acids. Circ Res 1976; 38 (Suppl. 01) 52-68.
• 28 Schön H R, Schelbert H B, Robinson G. et al. C-II labeled palmitic acid for the noninvasive evaluation of regional myocardial fatty acid metabolism with positron-computed tomography. I. Kinetics of C-ll palmitic acid in normal myocardium. Am Heart J 1982; 103: 532-47.
• 29 Schön H R, Senekowitsch R, Berg D. et al. Measurement of myocardial fatty acid metabolism: kinetics of iodine-123 heptadecanoic aicd in the normal dog heart. J Nucl Med 1986; 27: 1449-55.
• 30 Kloster G, Stöckling G. Determination of the rate limiting step in halofatty acid turnover in the heart. Radioakt Isotop Klin Forsch 1982; 15: 235-41.
• 31 Spitzer J J. Effect of lactate infusion on canine myocardial free fatty acid metabolism in vivo. Am J Physiol 1974; 226: 213-7.
• 32 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.
• 33 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.
• 34 Vyska K, Freundlieb C, Höck A, Feinendegen L E, Machulla H J, Stöcklin G. Myocardial imaging and measuring of myocardial fatty acid metabolism using omega-I-123-heptadecanoic acid. Adv Clin Cardiol 1980; 01: 422.
• 35 Wisneski J H, Gertz E W, Neese R A, Mayer M. Myocardial metabolism of free fatty acids. Studies with 14-C-labeled substrates in humans. J Clin Invest 1987; 79: 359-66.