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

Background-Cardiac hypertrophy is considered a necessary compensatory respo nse to sustained elevations of left ventricular (LV) wall stress. Methods and Results-To test this, we inhibited calcineurin with cyclosporin e (CsA) in the setting of surgically induced pressure overload in mice and examined in vivo parameters of ventricular volume and function using echoca rdiography. Normalized heart mass increased 45% by 5 weeks after thoracic a ortic banding (TAB; heart weight/body weight, 8.3+/-0.9 mg/g [mean+/-SE] ve rsus 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 TABS C sA treatment, we observed complete inhibition of hypertrophy (heart weight/ body weight, 5.2+/-0.3 mg/g at 5 weeks) and myocyte surface area (endocardi al and epicardial fractions). The mice tolerated abolition of hypertrophy w ith no signs of cardiovascular compromise, and 5-week mortality was not dif ferent from that of banded mice injected with vehicle (TAB+Veh). Despite ab olition of hypertrophy by CsA (LV mass by echo, 83+/-5 mg versus 83+/-2 mg unbanded), chamber size (end-diastolic volume, 33+/-6 mu L versus 37+/-1 mu L unbanded), and systolic ejection performance (ejection fraction, 97+/-2% versus 97+/-1% unbanded) were normal. LV mass differed si,significantly in TAB+Veh animals (103+/-5 mg, P<0.05), but chamber volume (end-diastolic vo lume, 44+/-6 mu L), 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 pre vented LV hypertrophy due to pressure overload. TAB mice treated with CsA m aintain normal LV size and systolic function.