Document Detail


High-dose norepinephrine induces disruption of myocardial extracellular matrix and left ventricular dilatation and dysfunction in a novel feline model.
MedLine Citation:
PMID:  16970269     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Intravenous norepinephrine (NE) at a dose of 1-6 microg/kg/minute can induce increased extracellular matrix (ECM) and hypertrophic cardiomyopathy. This study aimed to investigate the effects of a higher dose of NE on cardiac remodeling. METHODS: After intraperitoneal urethane-chloralose anesthesia, 7 cats (3.03 +/- 0.58 kg) received intravenous infusion of NE 30 microg/kg/minute for 3 hours. Aortic blood pressure and heart rate (HR) were measured by polygraphy at 0, 5, 15, 30, 60, 90, 120, and 180 minutes. Left ventricular size and ejection fraction (EF) were measured by M-mode echocardiography before and after NE administration. Histopathology was performed by hematoxylin-eosin, silver impregnation, and Sirius red staining. Activity of matrix metalloproteinases (MMP) in the left ventricle was measured by zymography. RESULTS: Mean blood pressure (mmHg) increased from 139 +/- 20 to 198 +/- 19, 187 +/- 23, and 166 +/- 16 at 15, 30, and 60 minutes, respectively, during NE infusion. HR (beats/minute) decreased from 214 +/- 10 to 158 +/- 28 at 15 minutes and then recovered gradually. The left ventricles showed significant dilatation (end-diastolic diameter: from 1.20 +/- 0.18 to 1.58 +/- 0.23cm, p=0.003; end-systolic diameter: from 0.62 +/- 0.23 to 1.35 +/- 0.29cm, p=0.002) and hypokinesia (EF: from 86.2 +/- 5.2 to 33.1 +/- 16.5%, p < 0.001). Histopathology revealed that left ventricular myocytes were elongated, wavy, and fragmented, while collagen fibers were overstretched, straightened, and disrupted. MMP-9 activity was significantly elevated (p = 0.003 vs. control), while MMP-2 activity was unchanged. CONCLUSION: High-dose NE increases MMP-9 activity and causes ECM disruption, left ventricular dilatation and dysfunction.
Authors:
Yung-Tsung Chiu; Ching-Chang Cheng; Nai-Nu Lin; Yi-Wen Hung; Ying-Tsung Chen; Shih-Lan Hsu; Ching-Shiang Chi; Yun-Ching Fu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the Chinese Medical Association : JCMA     Volume:  69     ISSN:  1726-4901     ISO Abbreviation:  J Chin Med Assoc     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-09-14     Completed Date:  2006-10-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  101174817     Medline TA:  J Chin Med Assoc     Country:  China (Republic : 1949- )    
Other Details:
Languages:  eng     Pagination:  343-50     Citation Subset:  IM    
Affiliation:
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Cats
Dilatation, Pathologic
Extracellular Matrix / drug effects*
Heart Rate / drug effects
Heart Ventricles / drug effects*,  pathology
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Myocardium / enzymology,  pathology
Norepinephrine / toxicity*
Ventricular Dysfunction, Left / chemically induced*
Chemical
Reg. No./Substance:
51-41-2/Norepinephrine; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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