{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:49:10Z","timestamp":1783039750477,"version":"3.54.6"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,5,16]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiac metabolic abnormalities are present in heart failure. Few studies have followed metabolic changes accompanying diastolic and systolic heart failure in the same model. We examined metabolic changes during the development of diastolic and severe systolic dysfunction in spontaneously hypertensive rats (SHR).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We serially measured myocardial glucose uptake rates with dynamic 2\u2010[\n              <jats:sup>18<\/jats:sup>\n              F] fluoro\u20102\u2010deoxy\u2010\n              <jats:sc>d<\/jats:sc>\n              \u2010glucose positron emission tomography in vivo in 9\u2010, 12\u2010, and 18\u2010month\u2010old SHR and Wistar Kyoto rats. Cardiac magnetic resonance imaging determined systolic function\u00a0(ejection fraction) and diastolic function (isovolumetric relaxation time) and left ventricular mass in the same rats. Cardiac metabolomics was performed at 12 and 18\u2009months in separate rats. At 12\u2009months, SHR hearts, compared with Wistar Kyoto hearts, demonstrated increased isovolumetric relaxation time and slightly reduced ejection fraction indicating diastolic and mild systolic dysfunction, respectively, and higher (versus 9\u2010month\u2010old SHR decreasing) 2\u2010[\n              <jats:sup>18<\/jats:sup>\n              F] fluoro\u20102\u2010deoxy\u2010\n              <jats:sc>d<\/jats:sc>\n              \u2010glucose uptake rates (Ki). At 18\u2009months, only few SHR hearts maintained similar abnormalities as 12\u2010month\u2010old SHR, while most exhibited severe systolic dysfunction, worsening diastolic function, and markedly reduced 2\u2010[\n              <jats:sup>18<\/jats:sup>\n              F] fluoro\u20102\u2010deoxy\u2010\n              <jats:sc>d<\/jats:sc>\n              \u2010glucose uptake rates. Left ventricular mass normalized to body weight was elevated in SHR, more pronounced with severe systolic dysfunction. Cardiac metabolite changes differed between SHR hearts at 12 and 18\u2009months, indicating progressive defects in fatty acid, glucose, branched chain amino acid, and ketone body metabolism.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Diastolic and severe systolic dysfunction in SHR are associated with decreasing cardiac glucose uptake, and progressive abnormalities in metabolite profiles. Whether and which metabolic changes trigger progressive heart failure needs to be established.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.026950","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T10:15:06Z","timestamp":1684145706000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Progressive Cardiac Metabolic Defects Accompany Diastolic and Severe Systolic Dysfunction in Spontaneously Hypertensive Rat Hearts"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-4835","authenticated-orcid":false,"given":"Jie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Minczuk","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"},{"name":"Department of Experimental Physiology and Pathophysiology Medical University of Bia\u0142ystok Bialystok Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9044-2464","authenticated-orcid":false,"given":"Qiao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon A.","family":"Kemp","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology and Metabolism University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Howell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology and Metabolism University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-4697","authenticated-orcid":false,"given":"Mahendra D.","family":"Chordia","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Jack","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7392-830X","authenticated-orcid":false,"given":"James T.","family":"Patrie","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3905-5490","authenticated-orcid":false,"given":"Zoraiz","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"},{"name":"Department of Computer Science University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2057-7731","authenticated-orcid":false,"given":"Christopher M.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiovascular Division University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1954-1988","authenticated-orcid":false,"given":"Frederick H.","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7238-7396","authenticated-orcid":false,"given":"Robert M.","family":"Carey","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology and Metabolism University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2683-9165","authenticated-orcid":false,"given":"Bijoy K.","family":"Kundu","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"},{"name":"Department of Biomedical Engineering University of Virginia Charlottesville VA"},{"name":"Cardiovascular Research Center University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3089-7766","authenticated-orcid":false,"given":"Susanna R.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology and Metabolism University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/20009666.2016.1264696"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq121"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq426"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000509"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051530"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0801369"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1511939"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318241"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00076-5"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.010926"},{"key":"e_1_3_2_12_2","first-page":"366","article-title":"Metabolic, functional and structural remodeling of spontaneously hypertensive rat hearts over time","volume":"59","author":"Li J","year":"2018","unstructured":"Li J, Huang Q, Cui S, Luo D, Desai S, Patrie J, Chordia M, Roy J, Kramer C, Epstein F, et al. 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