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Nitrogen-13 ammonia cardiac positron emission tomography in mice: effects of clonidine-induced changes in cardiac work on myocardial perfusion

  • Molecular Imaging
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Abstract

We explored the feasibility of imaging myocardial perfusion and of demonstrating the flow changes in response to reduction of cardiac work non-invasively in anesthetized mice using high spatial resolution, dedicated small-animal positron emission tomography (microPET). In 31 C57BL/6 mice anesthetized with pentobarbital or isoflurane, 13N-ammonia was injected intravenously and images were recorded with microPET from 4 to 20 min. Fifteen mice (group 1) were studied consecutively at baseline (BL) and after reduction of heart rate (HR) with intraperitoneal injection of clonidine (CLN) to investigate effects of CLN-induced reduction of cardiac work on myocardial 13N-ammonia uptake. Eight mice (group 2) were imaged repeatedly at BL and eight mice (group 3) twice after CLN to examine reproducibility. Total myocardial 13N-ammonia accumulation was determined from the transaxial images and normalized for injected dose (%ID). HR was 412±97 beats/min at BL and 212±44 beats/min after CLN (P<0.0001). In group 1, the %ID significantly decreased from 1.50%±0.27% at BL to 1.29%±0.28% after CLN (P<0.0001). In groups 2 and 3, reproducibility of %ID was good (y=0.96x+0.105, SEE=0.212%, r 2=0.749, P<0.0001). In conclusion, 13N-ammonia microPET imaging demonstrated non-invasively a reduction of myocardial perfusion induced by clonidine in mice. We believe this study is of importance as the first report on myocardial perfusion imaging and flow validation in in vivo mouse hearts with a left ventricular size of only 5 mm using 13N-ammonia and PET. MicroPET will aid in elucidating cardiac pathophysiology in transgenic mice and monitoring effects of gene therapies on myocardial perfusion.

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Acknowledgement

We thank Judy Edwards and Waldemar Ladno for assisting in the microPET studies, and Nagichettiar Satyamurthy and the cyclotron staff for providing 13N-ammonia. This work was supported by the U.S. Department of Energy Contract #DE-AC03-76-SF00012. The experiments were approved by the UCLA Animal Research Committee and performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals.

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Correspondence to Heinrich R. Schelbert.

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Inubushi, M., Jordan, M.C., Roos, K.P. et al. Nitrogen-13 ammonia cardiac positron emission tomography in mice: effects of clonidine-induced changes in cardiac work on myocardial perfusion. Eur J Nucl Med Mol Imaging 31, 110–116 (2004). https://doi.org/10.1007/s00259-003-1328-5

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