Impairment of the adrenergic reserve associated with exercise intolerance in a murine model of heart failure with preserved ejection fraction

• DOI: 10.1111/apha.14124
• Publication Date: 2024-03-04T10:06:30Z
• Authors: Lukas Semmler; Tobias Jeising; Judith Huettemeister; Marc Bathe‐Peters; Konstantina Georg...; Rashin Roshanbin; Paulina Sander; Shu Fu; David Bode; Felix Hohendanner; Burkert Pieske; Paolo Annibale; Gabriele G. Schia...; Christian U. Oeing; Frank R. Heinzel
• Keywords: Lusitropy; Myofilament; Exercise intolerance

Abstract Aim Exercise intolerance is the central symptom in patients with heart failure preserved ejection fraction. In present study, we investigated adrenergic reserve both vivo and cardiomyocytes of a murine cardiometabolic HFpEF model. Methods 12‐week‐old male C57BL/6J mice were fed regular chow (control) or high‐fat diet L‐NAME (HFpEF) for 15 weeks. At 27 weeks, performed (stress) echocardiography exercise testing measured its modulation by nitric oxide reactive oxygen species left ventricular cardiomyocytes. Results (preserved fraction, increased E/e', pulmonary congestion [wet lung weight/TL]) exhibited reduced capacity reduction stroke volume cardiac output stress. isolated from mice, sarcomere shortening had higher amplitude faster relaxation compared to control animals. Increased was caused shift myofilament calcium sensitivity. With addition isoproterenol, there no differences function between mice. This resulted inotropic lusitropic Preincubation inhibitors synthases glutathione partially restored HFpEF. Conclusion this model, on stimulation impaired. cardiomyocytes, found congruent loss reserve. contractility at rest, mediated nitro‐oxidative signaling.