Isoenzymic changes in myosin and hypertrophy; adaptation during chronic mechanical overload.

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Hypertrophy and a decrease in maximal contractile rate characterize the cardiac response to chronic mechanical overload. Both protect the myocardium, the first by increasing the number of contractile units, the second by maintaining the normal energy balance. Decrease in the contractile rate is correlated with (and is probably a function of) the decrease in myosin ATPase. This is due to an isoenzymic change, which has been demonstrated in the rat but remains hypothetical in man, towards a fetal form with a low ATPase activity. This redistribution, correlated with the degree of hypertrophy, is seen after stenosis or aortic insufficiency, infarction, a genetic tendency to hypertension and, after a longer latency, aorto-caval fistulae. The maximal contractile rate, measured for papillary muscle using the ‘zero-load clamp’ technique, is correlated with this isoenzymic change. Mechanisms associated with the onset of hypertrophy have been studied by continuous infusion of tyrosine C14 or lysine H3 as a protein synthesis precursor, and uridine H3 as an RNA precursor. While the rate of protein synthesis doubled after both aortic stenosis and aortic insufficiency, in the former case this doubling was seen after four days, while in the latter, it occurred only after 15 days. Myosin synthesis is normally twice as rapid as actin synthesis, and despite the increase in both, this proportion remained constant after four days of stenosis. The rise in protein synthesis preceded the increase in synthesis of ribosomal RNA 28 S fraction; thus the cardiac ribosomal stock is sufficiently large to allow an increase in protein synthesis in the absence of At novo ribosomal synthesis.