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Darbepoetin-alpha prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure.
Am J Physiol Heart Circ Physiol. 2008 Dec; 295(6):H2475-82.AJ

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.

Authors+Show Affiliations

Department of Internal Medicine, Henry Ford Heart and Vascular Institute, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18952719

Citation

Rastogi, Sharad, et al. "Darbepoetin-alpha Prevents Progressive Left Ventricular Dysfunction and Remodeling in Nonanemic Dogs With Heart Failure." American Journal of Physiology. Heart and Circulatory Physiology, vol. 295, no. 6, 2008, pp. H2475-82.
Rastogi S, Imai M, Sharov VG, et al. Darbepoetin-alpha prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure. Am J Physiol Heart Circ Physiol. 2008;295(6):H2475-82.
Rastogi, S., Imai, M., Sharov, V. G., Mishra, S., & Sabbah, H. N. (2008). Darbepoetin-alpha prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure. American Journal of Physiology. Heart and Circulatory Physiology, 295(6), H2475-82. https://doi.org/10.1152/ajpheart.00074.2008
Rastogi S, et al. Darbepoetin-alpha Prevents Progressive Left Ventricular Dysfunction and Remodeling in Nonanemic Dogs With Heart Failure. Am J Physiol Heart Circ Physiol. 2008;295(6):H2475-82. PubMed PMID: 18952719.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Darbepoetin-alpha prevents progressive left ventricular dysfunction and remodeling in nonanemic dogs with heart failure. AU - Rastogi,Sharad, AU - Imai,Makoto, AU - Sharov,Victor G, AU - Mishra,Sudhish, AU - Sabbah,Hani N, Y1 - 2008/10/24/ PY - 2008/10/28/pubmed PY - 2009/1/31/medline PY - 2008/10/28/entrez SP - H2475 EP - 82 JF - American journal of physiology. Heart and circulatory physiology JO - Am. J. Physiol. Heart Circ. Physiol. VL - 295 IS - 6 N2 - 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. SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/18952719/Darbepoetin_alpha_prevents_progressive_left_ventricular_dysfunction_and_remodeling_in_nonanemic_dogs_with_heart_failure_ L2 - http://www.physiology.org/doi/full/10.1152/ajpheart.00074.2008?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -