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(Circulation. 2000;101:2863.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Cardiac Hypertrophy Is Not a Required Compensatory Response to Short-Term Pressure Overload
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.
Correspondence to Joseph A. Hill, MD, PhD, Cardiovascular Division, University of Iowa College of Medicine, E318GH, UIHC, 200 Hawkins Dr, Iowa City, IA 52242-1081. E-mail joseph-hill{at}uiowa.edu
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.
Key Words: hypertrophy • cyclosporine • calcineurin
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