Abstract
Tissue accumulation of radiolabeled uridine, a precursor of uracil, reflects ribonucleic acid (RNA) synthesis and may be a marker of viability. To test this hypothesis, myocardial accumulation of H-3 uridine was compared to deoxyglucose uptake and histopathology in an experimental model of myocardial ischemia. In 18 Wistar rats the left coronary artery was occluded for 5, 10 or 60 minutes followed by reperfusion. Five hours later H-3 uridine and C-14 deoxyglucose were administered intravenously and the animals were sacrificed 45 minutes later. The left ventricle of each animal was divided into 12 segments and myocardial tracer accumulation was determined by measurement of tissue radioactivity. From the results of TTC staining, the animals were divided into 3 groups: Group I — ischemia without infarction (n=9); Group II — non-transmural infarction (n=4) and transmural infarction (n=5). Retention of uridine was observed in ischemic zones with enhanced deoxyglucose accumulation in Group I animals. Uridine accumulation was relatively preserved compared to slightly decreased deoxyglucose accumulation in regions of non-transmural infarction in Group II. In Group III, uridine accumulation decreased in parallel with deoxyglucose in zones of infarction. These results suggest that accumulation of radiolabeled uridine may be a useful indicator of viability in ischemic myocardium.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Goldstein RA, Klein MS, Welch MJ, Sobel BE. External assessment of myocardial metabolism with C-11 plamitatein vivo. J Nucl Med 1980; 21: 342–8.
Lerch RA, Ambos HD, Bergmann SR, Welch MJ, TerPo-gossian MM, Sobel BE. Localization of viable ischemic myocardium by positron-emission tomography with C-11-palmitate. Circulation 1981; 65: 731–8.
Marshall RC, Tillisch JH, Phelps ME, Huang SC, Carson R, Henze E, Schelbert HR. Identification and differentiating of resting myocardial ischemia in man with positron computed tomography, F-18 labeled fluorodeoxyglucose and N-13 ammonia. Circulation 1983; 67: 766–78.
Tillisch J, Brunken R, Marshall RC, Schwaiger M, Mandelkern M, Phelps M, Schelbert HR. Reversibility of cardiac wall motion abnormalities predicted by positron tomography. N Engl J Med 1986; 314: 884–8.
Schwaiger M, Schelbert HR, Ellison D, Hansen H, Yeatman L, Vinten-Johansen J, Selin C, Barrio J, Phelps ME. Sustained regional abnormalities in cardiac metabolism after transient ischemia in chronic dog model. J Am Coll Cardiol 1985; 6: 336–47.
Schwaiger M, Brunken R, Grover-Mckay M, Krivokapich J, Child J, Tillisch JH, Phelps ME, Schelbert HR. Regional myocardial metabolism in patients with acute myocardial infarction assessed by positron emission tomography. J Am Coll Cardiol 1986; 8: 800–8.
Brunken RC, Schwaiger M, Grower-Mckay M, Phelps ME, Tillisch JH, Schelbert HR. Positron emission tomography detects tissue metabolic activity in myocardial segments with persistent thallium perfusion defects. J Am Coll Cardiol 1987; 10: 557–67.
Camici P, Ferrannini E, Opie L. Myocardial metabolism in ischemic heart disease: basic principles and application of positron emission tomography. Prog Cardiovascular Dis 1989; 32 (3): 217–38.
Chouraqui P, Maddahi J, Henkin R, Karesh SM, Galie E, Bergman DS. Comparison of metabolic imaging with Iodine-123-Iodophenyl-9-Methyl Pentadecanoic acid and Thallium-201-chloride for assessment of patients with exercise induced myocardial ischemia. J Nucl Med 1991; 32: 447–52.
Bonow R, Dilsizian V, Cuocolo A, Bacharach S. Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction: comparison of thallium scintigraphy with reinjection and PET imaging with F-18 fluorodeoxyglucose. Circulation 1991; 83: 26–37.
Schwaiger M, Hicks R. The clinical role of metabolic imaging of the heart by positron emission tomography. J Nucl Med 1991; 32: 565–578.
Gould KL, Yoshida H, Hess MJ, Haynie M, Mullani N, Smalling RW. Myocardial metabolism of fluorodeoxyglucose compared to cell membrane integrity for the potassium analog Rubidium-82 for assessing infarct size in man by PET. J Nucl Med 1991; 31: 1–9.
Henrich MM, Vester E, von der Lohe E, Herzog H, Simon H, Kuikka JT, Feinendegen LE. Comparison of 2-F-18-2-de-oxyglucose and 15-(ortho-I-123-phenyl)-pentadecanoic acid uptake in persisting defects on thallium-201 tomography in myocardial infarction. J Nucl Med 1991; 32: 1353–7.
Wisneski JA, Gertz EW, Neese RA, Gruenke LD, Morris L, Craig JC. Metabolic fate of extracted glucose in normal human myocardium. J Clin Invest 1985; 76: 1819–27.
Bing RJ. Cardiac metabolism. Physiol Rev 1965; 45: 171–213.
Neely JR, Morgan HE. Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Ann Rev Physiol 1974; 36: 413–59.
Bodsch W, Takahashi K. Selective neuronal vulnerability to cerebral protein-and RNA-synthesis in the hippocampus of the gerbil brain. In: Bes A, Braquet P, Paoletti R, Siesjo BK (eds). Cerebral ischemia. 1984: 197–208.
Abe K, Araki T, Kogure K. Recovery from edema and protein synthesis differs between the cortex and caudate following transient focal cerebral ischemia in rats. J Neurochem 1988; 51(5): 1470–5.
Liszczak TM, Hedley-Whyte ET, Adams JF. Limitation of tetrazolium salts in delineating infarcted brain. Acta Neuropathol 1984; 65: 150–7.
Knapp WH, Helus F, Osterag H, Tilmans H, Kuebler W. Up-take and turnover of L-(N-13) glutamate in the normal human heart and patients with coronary artery disease. Eur J Nucl Med 1982; 7: 211–5.
Sokoloff L, Reivich M, Kennedy C, Rosiers MHD, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M. The (C-14) deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized albino rat. J Neurochem 1977; 28: 897–916.
Chen V, McDonough KH, Spitzer JJ. Effects of insulin on glucose metabolism in isolated heart myocytes from adult rats. Biochem Biophys Acta 1985; 846: 398–404.
Kalff V, Schwaiger M, Nguyen N, McClanahan TB, Gallagher KP. The relationship between myocardial blood flow and glucose uptake in ischemic canine myocardium determined with fluorine-18-deoxyglucose. J Nucl Med 1992; 33: 1346–52.
Wijns W, Melin JA, Leners N, Ferrant A, Keyeux A, Rahier J, Cogneau M, Michel C, Bol A, Robert A, Pouleur H, Charlier A, Beckers C. Accumulation of polymorphonuclear leukocytes in reperfused ischemic canine myocardium: relation with tissue viability assessed by fluorine-18-2-deoxyglucose uptake. J Nucl Med 1988; 29: 1826–32.
Shelton ME, Dence CS, Hwang DR, Herrero P, Welch MJ, Bergmann SR.In vivo delineation of myocardial hypoxia during coronary occlusion using fluorine-18 fluoromisonidazole and positron emission tomography: a potent approach for identification of jeopardized myocardium. J Am Coll Cardiol 1990; 16: 477–85.
Martin GV, Caldwell JH, Graham MM, Grierson JR, Kroll K, Cowan MJ, Lewellen TK, Rasey JS, Casciari JJ, Krohn KA. Noninvasive detection of hypoxic myocardium using fluorine-18-fluoromisonidazole and positron emission tomography. J Nucl Med 1992; 33: 2202–8.
Martin GV, Cerqueira MD, Caldwell JH, Rasey JS, Embree I, Krohn KA. Fluoromisonidazole: a metabolic marker of myocardial hypoxia. Circ Res 1990; 67: 240–4.
Gropler RJ, Bergmann SR. Myocardial viability — What is the definition. J Nucl Med 1991; 32: 10–12.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yaoita, H., Fischman, A.J., Strauss, H.W. et al. Uridine: A marker of myocardial viability after coronary occlusion and reperfusion. Int J Cardiac Imag 9, 273–280 (1993). https://doi.org/10.1007/BF01137154
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01137154