Title: Cardiac hypertrophy as early adjustments to a chronically sustained mechanical overload.
Abstract: There is a distinct inverse relationship between the force and the extent or velocity of muscle shortening in isolated muscle at a constant resting muscle length or in the intact heart with the preload and inotropic state held constant. In the normal ventricle, however, preload is usually allowed to increase as the aortic pressure is augmented, and the stroke volume tends to be maintained constant. Such complex interaction between increases in preload and afterload can be analyzed by a two dimensional framework in terms of the appropriateness of the matching between afterload and the level of inotropic state as modulated by preload. The initial response to chronic volume overload consists of near maximum use of the Frank-Starling mechanism. An increase in afterload due to the wall thinning and increased chamber size does not produce a fall of wall shortening. As an eccentric hypertrophy develops with series addition of sarcomeres, a delivery of much larger stroke volume is attained without any further use of the Frank-Starling mechanism, with a optimal extent of wall shortening per unit of circumference. Acute severe pressure overloading causes an acute after load mismatch despite the maximum use of preload reserve. Subsequently, chronic adaptation takes place with development of concentric hypertrophy which returns the ventricle to the control force-velocity curve. As wall thickening accomplishes a decrease in wall stress, wall shortening also becomes normal. Thus, chronic mechanical overload is initially adjusted by an adequate hypertrophy to correct afterload mismatch. Inadequate hypertrophy results in an elevation of wall stress and produces a decrease in stroke volume with the expenditure of the preload. The long standing hypertrophy may cause substantial depression of inotropic state with over heart failure. Further study will be needed how and when the pathological process overcomes the physiological adaptations.