Cardiac Hypertrophy Is Not a Required Compensatory Response to Short-Term Pressure Overload

Joseph A Hill; Mohsen Karimi; William Kutschke; Kathy Zimmerman; Robert M Weiss; Robin L Davisson; Zhengyi Wang; Richard E Kerber

doi:10.1161/01.CIR.101.24.2863

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Cardiac Hypertrophy Is Not a Required Compensatory Response to Short-Term Pressure Overload

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Cardiac Hypertrophy Is Not a Required Compensatory Response to Short-Term Pressure Overload

Joseph A Hill, Mohsen Karimi, William Kutschke, Kathy Zimmerman, Robert M Weiss, Robin L Davisson, Zhengyi Wang and Richard E Kerber

Circulation (New York, N.Y.), Vol.101(24), pp.2863-2869

06/20/2000

DOI: 10.1161/01.CIR.101.24.2863

PMID: 10859294

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Abstract

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 μL versus 37±1 μL 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 μL), 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.

Details

Title: Subtitle: Cardiac Hypertrophy Is Not a Required Compensatory Response to Short-Term Pressure Overload
Creators: Joseph A Hill - From the Division of Cardiovascular Diseases, Department of Internal Medicine (J.A.H., W.K., Z.W., R.E.K., R.M.W.), Department of Pharmacology (J.A.H.), Department of Veterans Affairs (J.A.H., K.Z., R.M.W.), Department of Surgery (M.K.), and Department of Anatomy and Cell Biology (R.L.D.), University of Iowa College of Medicine, Iowa City
Mohsen Karimi - From the Division of Cardiovascular Diseases, Department of Internal Medicine (J.A.H., W.K., Z.W., R.E.K., R.M.W.), Department of Pharmacology (J.A.H.), Department of Veterans Affairs (J.A.H., K.Z., R.M.W.), Department of Surgery (M.K.), and Department of Anatomy and Cell Biology (R.L.D.), University of Iowa College of Medicine, Iowa City
William Kutschke - From the Division of Cardiovascular Diseases, Department of Internal Medicine (J.A.H., W.K., Z.W., R.E.K., R.M.W.), Department of Pharmacology (J.A.H.), Department of Veterans Affairs (J.A.H., K.Z., R.M.W.), Department of Surgery (M.K.), and Department of Anatomy and Cell Biology (R.L.D.), University of Iowa College of Medicine, Iowa City
Kathy Zimmerman - From the Division of Cardiovascular Diseases, Department of Internal Medicine (J.A.H., W.K., Z.W., R.E.K., R.M.W.), Department of Pharmacology (J.A.H.), Department of Veterans Affairs (J.A.H., K.Z., R.M.W.), Department of Surgery (M.K.), and Department of Anatomy and Cell Biology (R.L.D.), University of Iowa College of Medicine, Iowa City
Robert M Weiss - From the Division of Cardiovascular Diseases, Department of Internal Medicine (J.A.H., W.K., Z.W., R.E.K., R.M.W.), Department of Pharmacology (J.A.H.), Department of Veterans Affairs (J.A.H., K.Z., R.M.W.), Department of Surgery (M.K.), and Department of Anatomy and Cell Biology (R.L.D.), University of Iowa College of Medicine, Iowa City
Robin L Davisson - From the Division of Cardiovascular Diseases, Department of Internal Medicine (J.A.H., W.K., Z.W., R.E.K., R.M.W.), Department of Pharmacology (J.A.H.), Department of Veterans Affairs (J.A.H., K.Z., R.M.W.), Department of Surgery (M.K.), and Department of Anatomy and Cell Biology (R.L.D.), University of Iowa College of Medicine, Iowa City
Zhengyi Wang - From the Division of Cardiovascular Diseases, Department of Internal Medicine (J.A.H., W.K., Z.W., R.E.K., R.M.W.), Department of Pharmacology (J.A.H.), Department of Veterans Affairs (J.A.H., K.Z., R.M.W.), Department of Surgery (M.K.), and Department of Anatomy and Cell Biology (R.L.D.), University of Iowa College of Medicine, Iowa City
Richard E Kerber - From the Division of Cardiovascular Diseases, Department of Internal Medicine (J.A.H., W.K., Z.W., R.E.K., R.M.W.), Department of Pharmacology (J.A.H.), Department of Veterans Affairs (J.A.H., K.Z., R.M.W.), Department of Surgery (M.K.), and Department of Anatomy and Cell Biology (R.L.D.), University of Iowa College of Medicine, Iowa City
Resource Type: Journal article
Publication Details: Circulation (New York, N.Y.), Vol.101(24), pp.2863-2869
DOI: 10.1161/01.CIR.101.24.2863
PMID: 10859294
NLM abbreviation: Circulation
ISSN: 0009-7322
eISSN: 1524-4539
Publisher: Lippincott Williams & Wilkins
Language: English
Date published: 06/20/2000
Academic Unit: Cardiovascular Medicine; Surgery; Cardiothoracic Surgery; Internal Medicine
Record Identifier: 9984094747802771

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