Document Detail


Chronic treatment of enbrel in rats with isoproterenol-induced congestive heart failure limits left ventricular dysfunction and remodeling.
MedLine Citation:
PMID:  12215284     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To investigate the effect of chronic treatment of enbrel (EB), a TNF-alpha antagonist, in a well defined congestive heart failure (CHF) rat model and test the hypothesis that chronic treatment of EB in CHF rats may limit the progression of Left ventricular (LV) dysfunction and structure remodeling and decrease cardiac IL-1beta levels. METHODS: We measured cardiac conformation, contractile performance and cytokines level in 8 age-matched normal adult rats (control group) and 8 rats with isoproterenol (ISO)-induced Heart failure (ISO group) and 8 rats with ISO-induced lesion but received EB treatment (EB group). RESULTS: LV end diastolic diameter and LV end systolic diameter in EB group were significantly less and LV fractional shortening was significantly larger than ISO group (9.2 +/- 0.3 mm vs 9.5 +/- 0.2 mm, 5.8 +/- 0.5 mm vs 6.5 +/- 0.3 mm, 0.37 +/- 0.03 vs 0.31 +/- 0.02, P < 0.05, P < 0.01, P < 0.01 respectively , but there was no significant difference of LV posterior wall thickness at end diastole between the two groups; LV end systolic pressure (P(ES)) dp/dt(max) in EB group were significantly greater than ISO group (104.8 +/- 4.6 mm Hg vs 98.4 +/- 4.9 mm Hg, 8395 +/- 940 mm Hg/s vs 6898 +/- 612 mm Hg, P < 0.05 P < 0.01 respectively), and LV end diastolic pressure (P(ED)) dp/dt(min), time constant of LV relaxation were significantly lower than ISO group (3.8 +/- 0.6 mm Hg vs 7.1 +/- 0.8 mm Hg, -5963 +/- 475 mm Hg/s vs-5030 +/- 316 mm Hg/s,15.4 +/- 0.8 ms vs 21.3 +/- 1.4 ms, P < 0.01, respectively . Although cardiac contractile performance in the EB group was greatly improved, there still was a big gap when compared with the control group. The ratio of LV weight to body weight in the EB group was significantly higher than control group 2.82 +/- 0.07 mg/g vs 2.28 +/- 0.08 mg/g, P < 0.01 but there was no significant difference when compared with the ISO group. There was no significant difference between the serum level of TNF-alpha in EB group and ISO group the it could not be detected in control group. TNF-alpha levels in LV of EB group was significantly higher than control group, 757.6 +/- 46.8 pg/g vs 367.5 +/- 22.7 pg/g, P < 0.01 but there was no significant difference when compared with ISO group. The IL-1beta level in LV of EB group was significantly lower than ISO group 356.2 +/- 28.5 pg/g vs 518.4 +/- 32.5 pg/g, P < 0.05 and it could not be detected in control group. The serum level of IL-1beta could not be detected in any rats. CONCLUSION: EB administered as soon as possible when ISO induced myocardial necrosis occurs can greatly improve cardiac contraction, and the improvement may be partly due to a decrease in the IL-1beta level in LV, besides the direct blocking effect of EB on TNF-alpha. EB can alleviate cardiac remodeling by its effect on LVEDD.
Authors:
Weimin Li; Runtao Gan; Guifang Sun
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chinese medical journal     Volume:  115     ISSN:  0366-6999     ISO Abbreviation:  Chin. Med. J.     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-09-06     Completed Date:  2003-01-28     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7513795     Medline TA:  Chin Med J (Engl)     Country:  China    
Other Details:
Languages:  eng     Pagination:  1166-9     Citation Subset:  IM    
Affiliation:
Departmant of Cardiology, The First Clinical College, Harbin Medical University, Harbin 150001 China. wml@public.hr.hl.cn
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight / drug effects
Echocardiography
Heart Failure / drug therapy*,  physiopathology,  ultrasonography
Immunoglobulin G / therapeutic use*
Interleukin-1 / analysis
Isoproterenol / pharmacology*
Male
Rats
Rats, Wistar
Receptors, Tumor Necrosis Factor / therapeutic use*
Tumor Necrosis Factor-alpha / analysis,  antagonists & inhibitors*
Ventricular Dysfunction, Left / prevention & control*
Chemical
Reg. No./Substance:
0/Immunoglobulin G; 0/Interleukin-1; 0/Receptors, Tumor Necrosis Factor; 0/Tumor Necrosis Factor-alpha; 185243-69-0/TNFR-Fc fusion protein; 7683-59-2/Isoproterenol

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