Biology of cardiac overload.

Mechanical overload in the heart induces two different types of adaptational mechanisms. (a) From a qualitative point of view, the maximum speed of shortening is depressed in relation to a myosin isoenzymic change responsible for decreased ATPase and, although the relaxation appears normal from a physiological point of view, the existence of an abnormality in Ca2+ uptake in the sarcoplasmic reticulum has been well documented. Both of these processes appear to improve efficiency by decreasing the heat produced per gram of tension. The existence of a large broadening of the action potential has now been well established, but it remains unexplained at the biochemical level. The functioning of mitochondria is rather controversial, and although it has been shown that they are both more abundant and smaller, the reason why their respiratory index changes remains unknown. (b) From a quantitative point of view, the adult heart adapts to overload by increasing its mass. This is mainly a consequence of a hypertrophy of the myocytes and a mitotic multiplication of nonmuscular cells. Data suggest that myocyte amitotic divisions may occur, at least in humans, and perhaps in very sizeable experimental hypertrophy. To this phenomenon has been added the development of polyploidy of myocyte nuclei, which seems to be specific to certain species. The stimulation of protein synthesis occurs very soon after pressure overload, and is delayed in volume overload; protein lysis also increases, although this is controversial. The process occurs whatever the proteins. This is accompanied by increased nuclear activity and a stimulation in RNA synthesis, which is especially precocious for messenger RNA. Among the very early events which could be potential signals for protein synthesis, attention has been focused on polyamine, RNA polymerase, and uridine kinase. The trigger mechanism, of course remains hypothetical. As a trigger for protein synthesis, several data suggest an increase in wall stress and stretch; a drop in efficiency is suggested as a trigger for qualitative changes.