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We investigate specific metabolic adaptations to direct future therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>An isoprenaline-injection female rat model (vs. sham) was studied at Day 3; recovery assessed at Day 7. Substrate uptake, metabolism, inflammation, and remodelling were investigated by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography, metabolomics, quantitative PCR, and western blot (WB). Isolated cardiomyocytes were patch-clamped during stress protocols for redox states of NAD(P)H\/FAD or [Ca2+]c, [Ca2+]m, and sarcomere length. Mitochondrial respiration was assessed by seahorse\/Clark electrode (glycolytic and \u03b2-oxidation substrates). Cardiac 18F-FDG metabolic rate was increased in takotsubo (P\u2009=\u20090.006), as was the expression of GLUT4-RNA\/GLUT1\/HK2-RNA and HK activity (all P\u2009&amp;lt;\u20090.05), with concomitant accumulation of glucose- and fructose-6-phosphates (P\u2009&amp;gt;\u20090.0001). Both lactate and pyruvate were lower (P\u2009&amp;lt;\u20090.05) despite increases in LDH-RNA and PDH (P\u2009&amp;lt;\u20090.05 both). \u03b2-Oxidation enzymes CPT1b-RNA and 3-ketoacyl-CoA thiolase were increased (P\u2009&amp;lt;\u20090.01) but malonyl-CoA (CPT-1 regulator) was upregulated (P\u2009=\u20090.01) with decreased fatty acids and acyl-carnitines levels (P\u2009=\u20090.0001\u20130.02). Krebs cycle intermediates \u03b1-ketoglutarate and succinyl-carnitine were reduced (P\u2009&amp;lt;\u20090.05) as was cellular ATP reporter dihydroorotate (P\u2009=\u20090.003). Mitochondrial Ca2+ uptake during high workload was impaired on Day 3 (P\u2009&amp;lt;\u20090.0001), inducing the oxidation of NAD(P)H and FAD (P\u2009=\u20090.03) but resolved by Day 7. There were no differences in mitochondrial respiratory function, sarcomere shortening, or [Ca2+] transients of isolated cardiomyocytes, implying preserved integrity of both mitochondria and cardiomyocyte. Inflammation and remodelling were upregulated\u2014increased CD68-RNA, collagen RNA\/protein, and skeletal actin RNA (all P\u2009&amp;lt;\u20090.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dysregulation of glucose and lipid metabolic pathways with decreases in final glycolytic and \u03b2-oxidation metabolites and reduced availability of Krebs intermediates characterizes takotsubo myocardium. The energetic deficit accompanies defective Ca2+ handling, inflammation, and upregulation of remodelling pathways, with the preservation of sarcomeric and mitochondrial integrity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvab081","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T15:11:08Z","timestamp":1615302668000},"page":"1932-1946","source":"Crossref","is-referenced-by-count":53,"title":["Metabolic alterations in a rat model of takotsubo syndrome"],"prefix":"10.1093","volume":"118","author":[{"given":"Nadine","family":"Godsman","sequence":"first","affiliation":[{"name":"Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Polwarth Building, Foresterhill , Aberdeen AB25 2ZD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6132-6037","authenticated-orcid":false,"given":"Michael","family":"Kohlhaas","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center (CHFC) , W\u00fcrzburg, Deutsches Zentrum f\u00fcr Herzinsuffizienz W\u00fcrzburg, Universit\u00e4tsklinikum W\u00fcrzburg, Am Schwarzenberg 15, Haus A15, 97078 W\u00fcrzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Nickel","sequence":"additional","affiliation":[{"name":"Comprehensive Heart Failure Center (CHFC) , W\u00fcrzburg, Deutsches Zentrum f\u00fcr Herzinsuffizienz W\u00fcrzburg, Universit\u00e4tsklinikum W\u00fcrzburg, Am Schwarzenberg 15, Haus A15, 97078 W\u00fcrzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Cheyne","sequence":"additional","affiliation":[{"name":"Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Polwarth Building, Foresterhill , Aberdeen AB25 2ZD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mingarelli","sequence":"additional","affiliation":[{"name":"Biomedical Physics, University of Aberdeen , Aberdeen AB25 2ZD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Schweiger","sequence":"additional","affiliation":[{"name":"John Mallard Scottish P.E.T. 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