Document Detail

Cardiac hypertrophy is not a required compensatory response to short-term pressure overload.
MedLine Citation:
PMID:  10859294     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Cardiac hypertrophy is considered a necessary compensatory response to sustained elevations of left ventricular (LV) wall stress. METHODS AND RESULTS: To test this, we inhibited calcineurin with cyclosporine (CsA) in the setting of surgically induced pressure overload in mice and examined in vivo parameters of ventricular volume and function using echocardiography. Normalized heart mass increased 45% by 5 weeks after thoracic aortic banding (TAB; heart weight/body weight, 8.3+/-0.9 mg/g [mean+/-SEM] versus 5. 7+/-0.1 mg/g unbanded, P<0.05). Similar increases were documented in the cell-surface area of isolated LV myocytes. In mice subjected to TAB+CsA treatment, we observed complete inhibition of hypertrophy (heart weight/body weight, 5.2+/-0.3 mg/g at 5 weeks) and myocyte surface area (endocardial and epicardial fractions). The mice tolerated abolition of hypertrophy with no signs of cardiovascular compromise, and 5-week mortality was not different from that of banded mice injected with vehicle (TAB+Veh). Despite abolition of hypertrophy by CsA (LV mass by echo, 83+/-5 mg versus 83+/-2 mg unbanded), chamber size (end-diastolic volume, 33+/-6 microL versus 37+/-1 microL unbanded), and systolic ejection performance (ejection fraction, 97+/-2% versus 97+/-1% unbanded) were normal. LV mass differed significantly in TAB+Veh animals (103+/-5 mg, P<0.05), but chamber volume (end-diastolic volume, 44+/-6 microL), ejection fraction (92+/-2%), and transstenotic pressure gradients (70+/-14 mm Hg in TAB+Veh versus 77+/-11 mm Hg in TAB+CsA) were not different. CONCLUSIONS: In this experimental setting, calcineurin blockade with CsA prevented LV hypertrophy due to pressure overload. TAB mice treated with CsA maintain normal LV size and systolic function.
J A Hill; M Karimi; W Kutschke; R L Davisson; K Zimmerman; Z Wang; R E Kerber; R M Weiss
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  101     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-07-13     Completed Date:  2000-07-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2863-9     Citation Subset:  AIM; IM    
Division of Cardiovascular Diseases, Department of Internal Medicine, Department of Veterans Affairs, University of Iowa College of Medicine, Iowa City 52242-1081, USA.
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MeSH Terms
Acute Disease
Adaptation, Physiological*
Aorta, Thoracic
Calcineurin / antagonists & inhibitors
Cardiomegaly / etiology*,  prevention & control,  ultrasonography
Cyclosporine / pharmacology
Enzyme Inhibitors / pharmacology
Hemodynamics / drug effects
Hypertension / complications*,  etiology,  physiopathology*,  ultrasonography
Mice, Inbred C57BL
Reg. No./Substance:
0/Enzyme Inhibitors; 59865-13-3/Cyclosporine; EC

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