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(Circulation Research. 2006;99:228.)
© 2006 American Heart Association, Inc.

Editorials

Containing Hypertrophy With a PICOT Fence

Gerald W. Dorn, II

From the Center for Molecular Cardiovascular Research, University of Cincinnati, Ohio.

Correspondence to Gerald W Dorn II MD, Hanna Professor and Director, Molecular Cardiovascular Research, 231 Albert Sabin Way, ML 0839, Cincinnati, OH 45267-0839. E-mail dorngw@ucmail.uc.edu

See related article, pages 307–314

Key Words: Protein kinase C • hypertrophy regression • transgenic mouse

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Cardiac hypertrophy is the common myocardial response to chronic hemodynamic overload. It currently affects nearly 5 million Americans and is responsible for &50 000 deaths annually.

	Why Is a Big Heart a Bad Thing?

 
From the perspective of cardiac mechanics, it seems surprising that cardiac hypertrophy is a killer. The physics of reactive hypertrophy date to the 19th century¹ and predict that hypertrophy will compensate for increased hemodynamic loading through normalization of ventricular wall stress, the phylogenetically conserved set point for cardiac load.² The Laplace relationship (stress= pr/h), describes wall stress increasing in direct proportion with intraluminal pressure (p) and chamber radius (r), but decreasing as wall thickness (h) grows. Accordingly, whether the ventricle dilates or is subjected to increased pressure, hypertrophic thickening of its walls should compensate.³ And it does. However, long-term functional compensation relies on the quality of hypertrophied myocardium being invariant as quantity increases, which is not the case. Multiple studies have defined molecular, cellular, and functional characteristics of reactive hypertrophy that differentiate it from normal myocardium and from cardiac enlargement caused by physiological conditioning.^4–6 Such findings gave rise to the notions of pathological and physiological hypertrophies⁷ and provide a mechanistic framework for why reactive hypertrophy ultimately fails,⁸ whereas physiological conditioning of the heart does not.

Cardiac hypertrophy also has effects unrelated to contractility and ventricular ejection performance. To quote Joseph Stalin out of context, "Quantity has a quality all its own", meaning that a steady quantitative change can create a sudden qualitative shift. The heart aptly demonstrates this principle because reactive hypertrophy and wall . . . [Full Text of this Article]

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