Assessment of longitudinal myocardial stiffness is not enough to evaluate diastolic function: what is the relevance of the stiffness of cardiomyocytes in the transverse direction?

cardial stiffness, not only of the ventricle as a whole, but in isolated myocytes as well, which has extended knowledge of both the cellular and molecular mechanisms that regulate myocardial stiffness. Thus, it has been possible to relate the incomplete relaxation phenomenon with an increase in myocardial stiffness, now under more strict control of the variables. However, all of those studies have considered longitudinal myocyte changes, and did not assess modifications that could occur in the transverse axis. Consideration of changes in the longitudinal and transverse axes of the myocytes is particularly important when we address the fact that the structure of the ventricular wall and its cellular distribution is based on helicoidal muscular beams that intercross, giving the ventricular wall the appearance of a grid, which implies that if we would perform a transverse cut to the left ventricle, we would observe in that same cut some myocytes in the longitudinal axis, and others in the transverse axis. That complex structure of the ventricular wall indicates that resistance to stretching, which occurs during each cardiac cycle, is not going to be the same when we observe the myocyte either longitudinally or transversely. Hence, mechanical stress is not only transmitted longitudinally but transversely as well. In other words, during the cardiac cycle, while some myocytes would be generating a given stiffness along the longitudinal axis, others are going to be generating it along the transverse axis. Consequently, the influence on stiffness of incomplete relaxation will not be the same either. In regard to this, Yoshikawa et al4 assessed the effect of incomplete relaxation on myocyte stiffness along the transverse axis, in a model of myocardial hypertrophy induced by chronic administration of isoproterenol. The authors conclude that an alteration in the formation of the actin and myosin cross-bridges, which induced a state of incomplete relaxation, determined the increase in the myocytes’ transverse stiffness. The administration of butanedione monoxime, an inhibitor of the actin-myosin interaction, reversed the stiffness increase, thus confirming the described phenomenon. Although the concept of transverse stiffness of myocytes has been described previously,5 in the study by Yoshikawa et al,4 this phenomerom the pioneering works of Otto Frank and Ernest H. Starling by the end of the 19th century and in the early 20th, myocardial function began to be the subject of intensive studies. However, the numerous studies published at the time only referred to myocardial contraction and not to the diastolic component. This overlooking of the diastolic component was possibly because ventricular filling was considered a completely passive process that occurred only as a result of pressure gradients. In the 1960 s, the first studies of diastolic function appeared and from there the interest in this phase of the cardiac cycle increased. Such interest has continued to the present day, when systole and diastole are equally considered. It should be added that in the past 2 decades the prevalence of heart failure with preserved ejection fraction has increased, and the prognosis of those patients with diastolic dysfunction is poor.1 Detailed study of the diastolic function, not only in intact animals or in patients, but in isolated organs as well, and even at the cellular level, has enabled clear differentiation of 2 phases in the diastolic component: isovolumic relaxation, and myocardial stiffness.