NDLI: Darbepoetin-alpha prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Rastogi, Sharad Imai, Makoto Sharov, Victor G. Mishra, Sudhish Sabbah, Hani N.
Description	Country affiliation: United States Author Affiliation: Rastogi S ( Department of Internal Medicine, Henry Ford Heart and Vascular Institute, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, USA.)
Abstract	In anemic patients with heart failure (HF), erythropoietin-type drugs can elicit clinical improvement. This study examined the effects of chronic monotherapy with darbepoetin-alpha (DARB) on left ventricular (LV) function and remodeling in nonanemic dogs with advanced HF. HF [LV ejection fraction (EF) approximately 25%] was produced in 14 dogs by intracoronary microembolizations. Dogs were randomized to once a week subcutaneous injection of DARB (1.0 microg/kg, n=7) or to no therapy (HF, n=7). All procedures were performed during cardiac catheterization under general anesthesia and under sterile conditions. LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were measured before the initiation of therapy and at the end of 3 mo of therapy. mRNA and protein expression of caspase-3, hypoxia inducible factor-1alpha, and the bone marrow-derived stem cell marker c-Kit were determined in LV tissue. In HF dogs, EDV and ESV increased and EF decreased after 3 mo of followup. Treatment with DARB prevented the increase in EDV, decreased ESV, and increased EF. DARB therapy also normalized the expression of HIF-1alpha and active caspase-3 and enhanced the expression of c-Kit. We conclude that chronic monotherapy with DARB prevents progressive LV dysfunction and dilation in nonanemic dogs with advanced HF. These results suggest that DARB elicits beneficial effects in HF that are independent of the presence of anemia.
File Format	HTM / HTML
ISSN	03636135
e-ISSN	15221539
DOI	10.1152/ajpheart.00074.2008
Journal	AJP: Heart and Circulatory Physiology
Issue Number	6
Volume Number	295
Language	English
Publisher	American Physiological Society
Publisher Date	2008-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Physiology Discipline Cardiology Cardiotonic Agents Pharmacology Erythropoietin Analogs & Derivatives Heart Failure Drug Therapy Ventricular Dysfunction, Left Prevention & Control Ventricular Remodeling Drug Effects Anemia Etiology Animals Bone Marrow Cells Pathology Administration & Dosage Caspase 3 Genetics Metabolism Darbepoetin Alfa Disease Models, Animal Disease Progression Complications Physiopathology Hematinics Hematopoietic Stem Cells Hypoxia-inducible Factor 1, Alpha Subunit Injections, Subcutaneous Myocardium Proto-oncogene Proteins C-kit Rna, Messenger Stroke Volume Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Cardiology and Cardiovascular Medicine

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