Abstract 16945: Aberrant Citric Acid Cycle Metabolites Temporally Coincide With Myocardial Dysfunction in a Rat Model of Stress Cardiomyopathy

• DOI: 10.1161/circ.148.suppl_1.16945
• Publication Date: 2023-11-06T07:38:29Z
• Authors: Amit Iyengar; Noah Weingarten; Jessica Dominic; Danika Meldrum; Rachel Wilson; Andrew Belec; Joyce Ho; Melissa Seiberlich; Pavan Atluri
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

Introduction: Stress cardiomyopathy is characterized by transient contractile dysfunction with a poorly understood mechanism. Targeting metabolic derangements has proven efficacious in chronic heart failure, but the role of metabolism acute cardiac ill-defined. Hypothesis: Characterizing any alterations stress may help identify potential therapeutic targets. Methods: Sprague-Dawley rats (350 ± 57 g) were given single intraperitoneal injection 75 mg/kg isoprenaline. Animals allocated into groups (N=30 each) based on designated time-points for assessment after injection: control (no injection), day 1, 3, and 7. Rats underwent left ventricular PV loop catheterization followed harvesting apical tissue. Targeted metabolomic analyses performed via LC-MS supplemented enzyme activity assays, qPCR, Western blotting. Results: Stroke work, output, ejection fraction all significantly reduced 1 recovery 7 (Figure A, p<0.05). tissue metabolomics revealed peaks nearly citric acid cycle metabolites, pyruvate, lactate that similarly correlated illness B). In tandem, anaplerotic amino acids rose injury while triglycerides decreased. Pyruvate dehydrogenase phosphorylation decreased expression pyruvate kinase C). However, no differences noted acylcarnitine levels despite increased serum fatty (all p>0.05). Conclusions: Profound rises metabolites accompanying increases are suggestive reprogramming setting energetic deficits. Notably, these trends differ from those found represent novel phenotypic characterization implications.