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Evaluation of cellular viability by quantitative autoradiographic study of myocardial uptake of a fatty acid analogue in isoproterenol-induced focal rat heart necrosis
Authors:Thierry Humbert  Cuong Luu-Duc  Michel Comet  Pierre Demenge
Institution:(1) Université Joseph Fourier, URA CNRS, 1287 Grenoble, France;(2) Laboratoire de Physiologie-Pharmacologie, Université Joseph Fourier, Domaine de la Merci, F-38700 La Tronche, France
Abstract:Previous studies led us to hypothesize that a fatty acid analogue, 15-p-iodophenyl-beta-methyl pentadecanoic acid (IMPPA or BMIPP), which is taken up but not quickly metabolized by heart cells, would be a more suitable tracer of cellular viability than thallium-201. Biodistribution studies of 1-14C-IMPPA in conscious, freely moving rats showed that the concentration ratio of radioactivity in the heart with respect to the blood was about 8 for at least 60 min after intravenous administration, permitting its use as a putative tracer in these conscious, freely moving rats. Thereafter, the myocardial uptake of14C-IMPPA was studied in isoproterenol-treated rats (daily treatment for 10 days in order to induce cardiac hypertrophy and necrotic foci) with respect to control ones. Comparison of myocardial localizations by quantitative autoradiography of the uptake of201Tl and14C-IMPPA with that of triphenyltetrazolium chloride (TTC) staining enabled comparative evaluation of nutritional blood flow, localization and uptake of14C-IMPPA and necrotic foci size. Distributions of14C-IMPPA and2011 T1 in control rats' hearts were homogeneous, like TTC staining. In infarcted hearts, areas of decreased14C-IMPPA uptake were nearly the same (100%±5%) as those unstained by TTC. These areas were larger than those showing a decrease in thallium uptake (about 70%±5% of the total scar size). Therefore, IMPPA seems to be a more accurate and sensitive indicator of necrosis localization compared with thallium. It may be a useful agent for assessment of myocardial viability by single photon emission tomography (SPET) imaging.
Keywords:15p-Iodophenyl-beta-methyl pentadecanoic acid (IMPPA)" target="_blank">gif" alt="beta" align="MIDDLE" BORDER="0">-methyl pentadecanoic acid (IMPPA)  Thallium-201  Viability  Quantitative autoradiography  Focal myocardial necrosis  Isoproterenol
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