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(Circulation. 2000;102:1045.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Microtubule Depolymerization Normalizes In Vivo Myocardial Contractile Function in Dogs With Pressure-Overload Left Ventricular Hypertrophy

Masaaki Koide, MD; Masayoshi Hamawaki, MD; Takahiro Narishige, MD; Hiroshi Sato, MD; Shintaro Nemoto, MD; Gilberto DeFreyte, BS; Michael R. Zile, MD; George Cooper, IV, MD; Blase A. Carabello, MD

From the Gazes Cardiac Research Institute, Medical University of South Carolina, and the Department of Veterans Affairs Medical Center, Charleston, SC.

Background—Because initially compensatory myocardial hypertrophy in response to pressure overloading may eventually decompensate to myocardial failure, mechanisms responsible for this transition have long been sought. One such mechanism established in vitro is densification of the cellular microtubule network, which imposes a viscous load that inhibits cardiocyte contraction.

Methods and Results—In the present study, we extended this in vitro finding to the in vivo level and tested the hypothesis that this cytoskeletal abnormality is important in the in vivo contractile dysfunction that occurs in experimental aortic stenosis in the adult dog. In 8 dogs in which gradual stenosis of the ascending aorta had caused severe left ventricular (LV) pressure overloading (gradient, 152±16 mm Hg) with contractile dysfunction, LV function was measured at baseline and 1 hour after the intravenous administration of colchicine. Cardiocytes obtained by biopsy before and after in vivo colchicine administration were examined in tandem. Microtubule depolymerization restored LV contractile function both in vivo and in vitro.

Conclusions—These and additional corroborative data show that increased cardiocyte microtubule network density is an important mechanism for the ventricular contractile dysfunction that develops in large mammals with adult-onset pressure-overload–induced cardiac hypertrophy.

Key Words: heart failure • hypertrophy • stenosis • cells • microtubules

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