Cardiac hypertrophy is not a required compensatory response to short- term pressure overload

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

Research output: Contribution to journalArticlepeer-review

244 Scopus citations

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 handing (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 ± 14mm Hg in TAB+Veh versus 77 ± 11 mmHg 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.

Original languageEnglish (US)
Pages (from-to)2863-2869
Number of pages7
JournalCirculation
Volume101
Issue number24
DOIs
StatePublished - Jun 20 2000

Keywords

  • Calcineurin
  • Cyclosporine
  • Hypertrophy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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