Structure, stress, and tissue repair in aortic valve leaflets.

During the normal cyclic operation of the aortic valve its leaflets are subjected to continual bending, shearing, and membrane stresses. In vivo studies of marked leaflets have shown that the bending stresses are greatest where leaflets are attached to the aortic wall. Pressure stresses during diastole also appear to be high in this region. The internal shearing stresses are difficult to predict because of the semifluid nature of the tissue in the attachment zone. In the present study a model of the attachment region incorporated measurements of leaflet motion from dogs in vivo and from histological sections. From these measurements bending and membrane stresses were derived in order to estimate the total stresses. In this region the total stresses in systole were negligible because membrane stresses are essentially zero, but those in diastole ranged from 76 to 95 g.mm-2 in the circumferential direction and from 37 to 44 g.mm-2 in the radial direction. The calculated stress suggests that excessive tissue wear and valve failure could occur in the absence of tissue replacement. From radioautographic studies of rat valves, proteins and complex sugars of the valve connective tissues were found to be regularly replaced in patterns predictable from the level of stresses.

Endothelial cell orientation on aortic valve leaflets.

Studies of the structure of blood vessels have commonly found that cells lining the vessels are lengthened in the direction of blood flow, presumably as an effect of shear stress. A study of aortic valves has, however, shown that endothelial cells covering both sides of aortic valve leaflets are arranged across the direction of flow. Aortic valve leaflets taken from seven adult mongrel dogs and fixed either open or closed with glutaraldehyde were studied with a scanning electron microscope after critical point drying. On both open and closed leaflets the endothelial cells tended to be aligned circumferentially with the free edge of the leaflet. The circumferential pattern was particularly unexpected on the leaflet surface facing the left ventricle because this surface could be expected to receive the full effect of shear stress from systolic blood flow. The finding suggested that surface cellular alignment on leaflets is determined by some force other than shear stress. The force apparently responsible for organising the collagenous layers in the leaflet, which are best adapted to bear stress, is diastolic blood pressure. Since the endothelium follows the same pattern of alignment as the layers of collagen it seems reasonable to conclude that endothelial orientation is also a response ultimately to pressure stress. The arrangement of the endothelium then serves as a readily observed indicator of those functional stresses that dominate and organise leaflet structure.

Stress sharing between the sinus and leaflets of canine aortic valve.

A knowledge of the behavior of the aortic valve sinuses is necessary to the understanding of stress sharing between the sinuses and the leaflets. Radiopaque markers were placed on the sinuses and the leaflets of dogs during cardiopulmonary bypass, and the movement of the markers was studied using fluoroscopy. The center of the sinus moved radially during each cardiac cycle, but in an inconsistent manner. The sinus was under a dual influence: the passive influence of aortic pressure and the active influence of myocardial contraction. The longitudinal curvature of the sinus showed no dimensional change, whereas the radius of the circumferential curvature decreased by 15.7% from systole to diastole. In diastole, the stress in the sinus was 6.1 g/mm2 and was 24.3 g/mm2 circumferentially and 12.1 g/mm2 radially in the leaflet. Histologically, the main stress-bearing component of the leaflet was made up of thick, dense, collagenous fibers oriented circumferentially. These fibers curved into the sinus wall instead of inserting straight into the aortic wall, thereby suggesting that the high stress in the leaflet is shared with the sinus and that continuity of the circumferential stress exists between the leaflet and the sinus. The leaflet does not pull inwardly on the aortic wall. In diastole, the sinus adapts to the new stress conditions in the leaflet by reducing its radius of circumferential curvature. This stress sharing is important for the longevity of the aortic valve.

Intramural stress as a causative factor in atherosclerotic lesions of the aortic valve.

Topographic distribution of atherosclerotic lesions of the aortic valve was investigated in rabbits on a 2%-cholesterol-enriched diet and related to distribution of intramural stress in the valve. Initially the lesions appeared at the base of the leaflet on the aortic face and with time spread further out into the leaflet and up the wall of the aortic sinus. In the leaflet, the lesion occurred only in the pressure-bearing part and was primarily composed of a mass of foam cells. By 10 weeks primary fatty plaques were still confined to the aortic face but fibroblasts within the leaflet had also taken up fat. Even after 33 weeks, the atheromatous plaque had not spread beyond the pressure-bearing part of the leaflet. From silicone rubber casts of the valve it was observed that only part of the leaflet was under pressure and the remaining leaflet sustained no pressure gradient. The maximum intramural stress occurred during diastole on the pressure-bearing part. In systole, the blood flow produced shear stress on the entire leaflet. Hence, occurrence of atherosclerotic lesions only in the area of maximum intramural stress suggests that intramural stress and not shear stress plays an important role in accelerating the process of atherosclerosis.

Role of mechanical stress in calcification of aortic bioprosthetic valves.

Calcification of bioprostheses used for heart valve replacement is a serious problem, since it causes bioprosthetic dysfunction. In vivo, bioprostheses are subjected to large mechanical stresses during each cardiac cycle. We investigated whether stresses play a major role in calcification of bioprostheses. Previous studies of Carpentier-Edwards porcine, Hancock porcine, and Ionescu-Shiley pericardial bioprostheses indicated that the highest stresses occurred in the areas of greatest flexion of the leaflet. In porcine bioprostheses, stresses were greater in the commissural region than at the base, and were compressive on the aortic surface of the leaflet. The pericardial tissue showed shear deformation in the zone of flexion. In the present study, the three types of bioprostheses were implanted in the aortic position in calves to investigate the development, location, and distribution of calcification. Visual, radiographic, and histologic techniques were used. All bioprostheses showed calcification which began in the area of leaflet flexion. In porcine bioprostheses, calcification occurred earlier in the commissural region than at the base. The earliest calcific deposits were localized within collagen cords on the aortic surface of the leaflets. In pericardial bioprostheses, calcification occurred at multiple foci along the zone of leaflet flexion and was located between and within layers of collagen along planes parallel to the leaflet surface. Hence calcification in all bioprostheses began in the areas of greatest stress. In porcine bioprostheses, calcification was present where collagen fibers are likely to have been damaged by compressive stresses. In pericardial bioprostheses, calcification was found along the planes of shear where structural integrity is likely to have been disrupted by the sliding of individual layers of collagen over each other. It is concluded that mechanical stresses initiate calcification by damaging the structural integrity of the leaflet tissue. Therefore, calcification of bioprostheses can be inhibited by reducing functional stresses through the modification of design and tissue properties to duplicate those of the natural aortic valve.

Stresses of natural versus prosthetic aortic valve leaflets in vivo.

During normal function of the aortic valve, the aortic leaflets undergo not only cyclic loading and unloading but also cyclic reversal of their curvature. The stresses induced in the leaflet due to these variations have been computed using a new concept based on the structure of the leaflet. Membrane stresses have been related to the pressure difference across the leaflet and bending stresses to the leaflet curvature. Total stresses were obtained by adding the two stresses. Total stresses in bioprosthetic and synthetic leaflets also were computed using the same approach. In systole, the natural leaflet is subjected to much lower total stress than a bioprosthetic or a synthetic leaflet. The natural leaflet is not subjected to compressive stresses during the cardiac cycle, whereas bioprosthetic and synthetic leaflets must sustain compressive stresses during systole. The differences in stress patterns of these leaflets indicate that there is a difference in their longevity.

The effect of denervation on bony overgrowth after below knee amputation in rats.

Bony overgrowth of amputated limbs of children is an infrequent but difficult problem. This article presents the hypothesis that the bony overgrowth is under nerve control and may represent an abortive form of partial limb regeneration. Tested in young rats, denervation produces a significant reduction in the mass and length of the bony overgrowth and a reduced rate of periosteal cell mitosis.

The dynamic aortic root. Its role in aortic valve function.

By attaching appropriate measuring devices to the wall of an intact aortic root at the level of leaflet coaptation, we have measured a 16 per cent diameter change during each cardiac cycle. The dimensional changes observed can by themselves explain aortic valve function and obviate the postulation that the leaflets shorten and lengthen during each cardiac cycle. The tissue composition of the aortic root and leaflets is more compatible with this theory than with other postulations. Such a dynamic aortic root may explain the longevity of the actual aortic leaflets, in that leaflet fatigue stress is minimized by changes in aortic root dimension.