Myocardial Plasticity and Heart-Chamber Stability

MYOCARDIAL PLASTICITY AND HEART-CHAMBER STABILITY DAVID M. REGEN* Introduction The myocardium is normally quite stable, in the sense that no sector of a chamber wall becomes progressively longer, thinner, and weaker until it blows out, and no chamber dilates progressively until it occupies so much of the chest as to interfere with ventilation. Because the myocardium usually achieves stability despite a wide range of normal and abnormal burdens even with substantial myocardial disease, the issue of myocardial stability gets little scientific attention. This essay will consider the requirements for stability, the factors tending to destabilize and stabilize the myocardium, and possible mechanisms of decompensation. Central to this matter is the fact that average arterial pressure must assume that value (set point) that causes fluid excretion to equal fluid intake. If average arterial pressure is below its set point, fluid excretion will be less than fluid intake, the positive fluid balance resulting in increased end-diastolic volumes. This normally increases cardiac output and arterial pressure until the set point is reached where fluid balance occurs. In light of this principle (which I call Guyton's law), one can see that a heart chamber will be stable if a durable increase of its diastolic circumferential length results in a durable increase of cardiac output; and a heart chamber will be unstable and will decompensate if a durable increase of its diastolic circumferential length does not result in a durable increase of cardiac output. A similar but more complicated rule applies to any sector of the chamber's wall. Following a sudden and sustained increase of end-diastolic volume, the immediate response is due to increased sarcomere lengths, the longer sarcomeres being more able to develop stress and more able to ?Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232.© 1991 by The University of Chicago. All rights reserved. 003 1-5982/91/3402-0728$01 .00 162 J David M. Regen ¦ Heart-Chamber Stability shorten. This can increase stroke volume, cardiac output, and arterial pressure even if the heart is decompensating. However, during subsequent hours and days, the number of sarcomeres between ends of the longer myocytes increases eventually in proportion to the increase of average myocyte length. Thus, within a week or so, sarcomere lengths decline toward normal, as do the abilities to develop stress and to shorten. As this occurs (with a constant elevation of end-diastolic volume ), average cardiac output declines. In a stable heart, it declines to a value which is greater than that which prevailed prior to elevation of end-diastolic volume. In a decompensating heart, it declines to a value that is the same as or less than that which prevailed before the elevation of end-diastolic volume. Thus, the remodeling that normalizes sarcomere length is instrumental in the decompensatory process. It tends to make the myocardium unstable. If average cardiac output fails to increase with average end-diastolic volume, positive fluid balance will be endless and at least one heart chamber will dilate endlessly. Cardiac output is stroke volume multiplied by heart rate. In principle, cardiac output could fail to increase with end-diastolic volume if heart rate were to become inversely proportional to end-diastolic volume (or worse), but there is no mechanism to produce such a relation. Stroke volume is end-diastolic volume multiplied by ejection fraction. In fact, decompensation occurs when average stroke volume does not increase with average end-diastolic volume, and this occurs when average ejection fraction becomes inversely proportional to average end-diastolic volume (or worse). Average ejection fraction depends on three independent factors—stress afterload (a weighted average of stresses experienced by the myocardium during ejection), contractility (the stress that the myocardium could develop at average end-diastolic distension if contraction were entirely isovolumic), and mobility or shortening ability (the ejection fraction or shortening fraction that would occur from average end-diastolic distension or extension if afterload were zero). Contractility and mobility are favorable to ejection fraction; and either or both might become inversely dependent on end-diastolic volume, such that each increase of end-diastolic volume is followed by a decline of contractility and/or mobility sufficient to reduce ejection fraction in...