Chronic Therapy With a Partial Adenosine A1-Receptor Agonist Improves Left Ventricular Function and Remodeling in Dogs With Advanced Heart Failure
| Autor: | Hani N. Sabbah, Mengjun Wang, Sharad Rastogi, Barbara Albrecht-Küpper, Kefei Zhang, Smita Kohli, Nicole Diedrichs, Ramesh C. Gupta, Katja Zimmermann |
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| Rok vydání: | 2013 |
| Předmět: |
Agonist
medicine.medical_specialty medicine.drug_class Aminopyridines Ventricular Function Left Article Adenosine A1 receptor Dogs Internal medicine Ventricular Pressure medicine Natriuretic peptide Animals Ventricular remodeling Heart Failure Ejection fraction Ventricular Remodeling business.industry Hemodynamics Stroke Volume medicine.disease Adenosine Adenosine receptor Echocardiography Doppler Adenosine A1 Receptor Agonists Thiazoles Endocrinology Heart failure Cardiology Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Circulation: Heart Failure. 6:563-571 |
| ISSN: | 1941-3297 1941-3289 |
| DOI: | 10.1161/circheartfailure.112.000208 |
| Popis: | Background— Adenosine elicits cardioprotection through A1-receptor activation. Therapy with adenosine A1-receptor agonists, however, is limited by undesirable actions of full agonism, such as bradycardia. This study examined the effects of capadenoson (CAP), a partial adenosine A1-receptor agonist, on left ventricular (LV) function and remodeling in dogs with heart failure. Methods and Results— Twelve dogs with microembolization-induced heart failure were randomized to 12 weeks oral therapy with CAP (7.5 mg BID; n=6) or to no therapy (control; n=6). LV end-diastolic and end-systolic volumes, ejection fraction, plasma norepinephrine, and n-terminal pro–brain natriuretic peptide were measured before (pre) and 1 and 12 weeks after therapy (post). LV tissue obtained at post was used to assess volume fraction of interstitial fibrosis, sarcoplasmic reticulum calcium ATPase-2a activity, expression of mitochondria uncoupling proteins (UCP) and glucose transporters (GLUT). In controls, end-diastolic and end-systolic volumes increased and ejection fraction decreased significantly from pre to post (ejection fraction, 30±2 versus 27±1%; P P P Conclusions— In heart failure dogs, CAP improves LV function and prevents progressive remodeling. Improvement of LV systolic function occurs early after initiating therapy. The results support development of partial adenosine A1-receptor agonists for the treatment of chronic heart failure. |
| Databáze: | OpenAIRE |
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