Cardiocyte cytoskeleton in hypertrophied myocardium.

Abstract

The Frank-Starling mechanism, by which load directly regulates muscle length and thus performance is the means by which the mechanics and energetics of cardiac muscle are regulated on a beat-to-beat basis. When this short-term compensation for increased load is insufficient, the long-term compensation of cardiac hypertrophy ensues. The simplest and most direct mechanism for load regulation of cardiac mass would obtain if an analog of the short-term Frank-Starling mechanism of functional regulation operated in the long-term time domain of mass regulation; that is, if heart muscle were able to directly transduce increased load into growth. It is now clear that load does indeed serve as a direct regulator of cardiac mass in the adult. Cardiac hypertrophy, at the levels of intact animal, isolated tissue, and cultured cells, is a direct response of the adult mammalian cardiocyte to increased load, modified by but without the requisite involvement of factors external to the cell. The extent to which such hypertrophy is compensatory is critically dependent on the type of hemodynamic overload that serves as the hypertrophic stimulus. Thus, cardiac hypertrophy is not intrinsically maladaptive; rather, it is the nature of the inducing load rather than hypertrophy itself that is responsible for the frequent deterioration of initially compensatory hypertrophy into the congestive heart failure state. As one example reviewed here of this load specificity of maladaptation, increased microtubule network density is a persistent feature of severely pressure overloaded, hypertrophied and failing myocardium which imposes a viscous load on active myofilaments during contraction.