Structural Basis for the Ascending Limb of Left Ventricular Function

Abstract

Midwall sarcomere lengths near maximal have been reported at left ventricular end-diastolic pressures at the upper limits of normal, but an ascending limb of cardiac function can exist at much higher filling pressures. Accordingly, an analysis was made of sarcomere length distributions across the left ventricular wall over a range of end-diastolic pressures between 2 and 20 mm Hg. In 11 dogs, significant ascending limbs of ventricular function were documented at filling pressures between 2 and 12 mm Hg and between 12 and 20 mm Hg. Nine hearts were arrested and rapidly fixed in diastole with intracoronary glutaraldehyde perfusion, and tissues from five sites equally distributed across the left ventricular free wall were examined by electron microscopy. At filling pressures at the lower end of the normal range (2, 6, and 12 mm Hg), an uneven distribution of sarcomere lengths across the wall was noted: mean sarcomere lengths were shortest at the subendocardial layer, longest at a site between the subendocardial and the midwall layers, and then progressively shorter toward the epicardium. All differences were highly significant. At an end-diastolic pressure of 20 mm Hg, the difference in sarcomere lengths between layers was small; sarcomere lengths decreased only slightly from endocardium to epicardium. Despite maximal sarcomere lengths just inside the midwall in hearts fixed at 12 mm Hg (2.253µ), sarcomere lengths in other layers-the subendocardial and the subepicardial regions-were increased substantially from 2.129 and 2.183µ, respectively, at 12 mm Hg to 2.283 and 2.247µ at 20 mm Hg ( P < 0.001 and P < 0.002, respectively). Therefore, sarcomeres from all layers of the wall increase in length up to a filling pressure of 12 mm Hg; however, as filling pressure is increased further, only short sarcomeres from the subendocardial and the subepicardial layers are recruited. The latter mechanism forms the ultrastructural basis for the ascending limb of normal ventricular function at elevated left ventricular filling pressures.