| A growth hormone secretagogue prevents ischemic-induced mortality independently of the growth hormone pathway in dogs with chronic dilated cardiomyopathy. | |
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MedLine Citation:
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PMID: 12750438 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To determine the functional role of growth hormone (GH) secretagogue in myocardium with ischemia, left ventricular (LV) pressure gauge, wall thickness crystals, coronary occluder, pacers, and catheters were implanted in 26 dogs. Beginning 1 week after ventricular pacing (240 beats/min) was initiated, dogs were treated (s.c.) with GH releasing peptide-6 (GHRP-6, n = 8, 0.2 mg/kg/day), GH (n = 7, 0.06 mg/kg/day), or vehicle (n = 11). Two weeks of pacing was associated with similar decreases in LV pressure, rate of change of LV pressure, systolic wall thickening (WT), and an increase in left atrial pressure in all groups. Coronary artery occlusion (CAO) resulted in a similar loss of WT in ischemic regions, which did not recover during reperfusion period in all groups. WT in nonischemic regions, however, was enhanced in the GHRP-6 group compared with the GH and vehicle groups, e.g., increase of WT after 1 h of reperfusion was greater (p <0.05) in the GHRP-6 (+53 +/- 8%) than in the GH (+14 +/- 12%) or (+14 +/- 6%). There were no differences in myocardial blood flow, hemodynamics, or arrhythmic beats among all groups during CAO and reperfusion periods. Strikingly, no dogs in the GHRP-6 group died during CAO, whereas the survival rates for GH and vehicle groups were 57 and 55%, respectively. Our data demonstrate, for the first time, that chronic therapy with a GH secretagogue prevents sudden death in dogs with dilated cardiomyopathy subjected to acute ischemia. This seems to be related to an enhanced nonischemic compensatory mechanism mediated by the GH secretagogue receptors rather than via the GH/insulin growth factor-1 pathway. |
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Authors:
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You-Tang Shen; Joseph J Lynch; Richard J Hargreaves; Robert J Gould |
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Publication Detail:
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Type: Journal Article Date: 2003-05-15 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 306 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 2003 Aug |
Date Detail:
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Created Date: 2003-07-21 Completed Date: 2003-08-28 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: United States |
Other Details:
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Languages: eng Pagination: 815-20 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA. you-tang_shen@merck.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiomyopathy, Dilated / complications*, mortality Chronic Disease Coronary Stenosis / complications Disease Models, Animal Dogs Growth Hormone / therapeutic use* Heart Ventricles / drug effects Hemodynamics / drug effects Mortality Myocardial Contraction Myocardial Ischemia / complications*, mortality Myocardial Reperfusion Oligopeptides / therapeutic use* Reperfusion Injury / prevention & control* |
| Chemical | |
Reg. No./Substance:
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0/Oligopeptides; 87616-84-0/growth hormone releasing hexapeptide; 9002-72-6/Growth Hormone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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