β3-Adrenergic receptor antagonist improves exercise performance in pacing-induced heart failure
| Autor: | Hiroshi Hasegawa, Qing-Hua Han, Heng-Jie Cheng, Atsushi Morimoto, Satoshi Masutani, Che Ping Cheng, William C. Little |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Contraction (grammar) Physiology medicine.drug_class Physical Exertion Diastole Stimulation Contractility Ventricular Dysfunction Left Integrative Cardiovascular Physiology and Pathophysiology Dogs Physiology (medical) Internal medicine Heart rate medicine Animals Heart Failure Exercise Tolerance business.industry Antagonist medicine.disease Receptor antagonist Treatment Outcome Receptors Adrenergic beta-3 Heart failure Exercise Test Cardiology Adrenergic beta-3 Receptor Antagonists Cardiology and Cardiovascular Medicine business |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 305:H923-H930 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00371.2012 |
| Popis: | In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise. We have previously shown that in HF at rest stimulation of β3-adrenergic receptors by endogenous catecholamine depresses LV contraction and relaxation. β3-Adrenergic receptors are activated at higher concentrations of catecholamine. Thus exercise may cause increased stimulation of cardiac β3-adrenergic receptors and contribute to this abnormal response. We assessed the effect of L-748,337 (50 μg/kg iv), a selective β3-adrenergic receptor antagonist (β3-ANT), on LV dynamics during exercise in 12 chronically instrumented dogs with pacing-induced HF. Compared with HF at rest, exercise increased LV end-systolic pressure (PES), minimum LV pressure (LVPmin), and the time constant of LV relaxation (τ) with an upward shift of early diastolic portion of LV pressure-volume loop. LV contractility decreased and arterial elastance (EA) increased. LV arterial coupling (EES/EA) (0.40 vs. 0.51) was impaired. Compared with exercise in HF preparation, exercise after β3-ANT caused similar increases in heart rate and PES but significantly decreased τ (34.9 vs. 38.3 ms) and LVPmin with a downward shift of the early diastolic portion of LV pressure-volume loop and further augmented dV/d tmax. Both EES and EES/EA (0.68 vs. 0.40) were increased. LV mechanical efficiency improved from 0.39 to 0.53. In conclusion, after HF, β3-ANT improves LV diastolic filling; increases LV contractility, LV arterial coupling, and mechanical efficiency; and improves exercise performance. |
| Databáze: | OpenAIRE |
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