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Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice
Published on: May 13, 2019
Microtubule depolymerization normalizes in vivo myocardial contractile function in dogs with pressure-overload left
M Koide1, M Hamawaki, T Narishige
1Gazes Cardiac Research Institute, Medical University of South Carolina, Charleston, SC 29403, USA.
Circulation
|August 30, 2000
Summary
Increased microtubule density in heart cells contributes to contractile dysfunction during pressure overload. Depolymerizing microtubules with colchicine restored heart function in dogs with experimental aortic stenosis.
Area of Science:
- Cardiovascular Physiology
- Cell Biology
- Biochemistry
Background:
- Myocardial hypertrophy can progress to heart failure.
- Increased microtubule network density is a proposed mechanism for this transition.
- This cytoskeletal abnormality inhibits cardiocyte contraction by imposing a viscous load.
Purpose of the Study:
- To investigate the role of increased cardiocyte microtubule network density in vivo.
- To test if this cytoskeletal abnormality contributes to contractile dysfunction in experimental aortic stenosis.
- To determine if microtubule depolymerization can restore cardiac function.
Main Methods:
- Induction of experimental aortic stenosis in adult dogs to create pressure overload.
- Measurement of left ventricular (LV) function before and after colchicine administration.
- Examination of cardiocytes via biopsy before and after colchicine treatment.
Main Results:
- Dogs with severe LV pressure overload and contractile dysfunction were studied.
- Intravenous colchicine administration led to microtubule depolymerization.
- Microtubule depolymerization restored LV contractile function both in vivo and in vitro.
Conclusions:
- Increased cardiocyte microtubule network density is a key mechanism in ventricular contractile dysfunction.
- This dysfunction occurs in large mammals with adult-onset pressure-overload-induced cardiac hypertrophy.
- Targeting the microtubule network may offer therapeutic potential for heart failure.
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