3. Genesis of cardiac hypertrophy

During acute overloading the total and ex- ternal work of the heart chamber and for each fiber unit increase. Wall stress, expressed as force per unit cross-sectional area, and oxygen consumption per weight unit increase concomi- tantly. These two factors are among the possible triggers of the many metabolic and cellular events occurring during early hypertrophy, the principal components of these being increased protein synthesis4R9 lo. This synthesis is generally local- ized to the specific region under stress. Through a delicate feedback system the process continues to a point where the triggering factors are almost or totally normalized. Thus, there is a funda- mental and ‘probably linear relationship between the degree of hypertrophy and the degree of loading.

Although more subtle indices of contractility, involving the velocity of contraction, are reduced in hypertrophy’* 13, most studies indicate that the hypertrophic myocardium may create as much force per weight unit as normal. heart muscleB9. Several studies indicate that pressure work gives a steeper increase in myocardial oxygen con- sumption and wall tension than flow work8. Accordingly, the increase in muscle mass is usu- ally greater in pressure loading10.

Since both types of overload probably elicit hypertrophy by the same general mechanisms, one would think that the process would have a similar distribution in both conditions. Some observations indicate, however, that pure press-

ure work gives a symmetrically distributed hyper- trophy, and a flow load a more assymmetrical one151h. Such differences may be relevant to the interpretation of ECG patterns seen in volume loading (paper 3).

Several factors may disturb the dynamic state of equilibrium between chamber stress and thc anatomical response to it:

a) Both the development and the regression of hypertrophy require time. I n human, at least months of stable loading are probably needed.

b) The anatomic-physiologic relationship seems generally to be closer in congenital than in acquired heart disease. Possible explanation5 may be a greater potential for compensatory hypertrophy in the former and a greater ten- dency to concomitant fibrosis in the latter.

c) Several associated diseases of the hcart may modify the hypertrophic response. This ap- plies especially to coronary heart disease and hypertrophic cardiomyopathy. The latter is characterized by a muscle mass out of pro- portion to the load. The best established ex- ample is hypertrophic obstructive cardiomyo- pathy; another may be the hypertrophy in subjects with Turner phenotype and pulmon- ary stenosis described in paper 4”.

In addition, methodological problems of a more general nature arise in practical compari- sons of anatomy and physiology.