Mano J. Thubrikar

Patterns of calcific deposits in operatively excised stenotic or purely regurgitant aortic valves and their relation to mechanical stress

Two hundred twenty-one aortic cusps from 96 patients who underwent aortic valve replacement were examined. Of all the cusps that showed any calcific deposits, 87% had calcific deposits in 1 of 2 specific patterns: a coaptation pattern, where calcific deposits occurred along the line of cusp coaptation, and a radial pattern, where calcific deposits occurred as spokes spread inward from the cusp attachment to the center of the cusp. This was true irrespective of the patients sex or age, the type of disease, and the type of valve or the extent of calcific deposits. These patterns of calcific deposits relate to the area of maximal cusp flexion and, hence, maximal mechanical stress. It is therefore concluded that calcific deposits in aortic valve cusps occur in specific patterns in most cases, and that mechanical stress may be the initiating or accelerating factor in the calcification of these cusps.

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.

Inhibition of atherosclerosis associated with reduction of arterial intramural stress in rabbits.

Atherosclerotic lesions commonly develop at arterial branch sites, which are also the sites of high arterial Intramural stress produced by Intralumlnal pressure. We Investigated the effect of reduced Intramural stress on the development of atherosclerotic lesions. We exposed the origin of the left renal artery In five rabbits and the aortic bifurcation in another five, lowered the mean arterial pressure to 35 to 45 mm Hg, and poured a dental acrylic liquid around the branch to form a rigid cast When the rabbits recovered and the arterial pressure Increased to normal, the casts prevented the arteries from expanding, thereby maintaining a low Intramural stress. These rabbits plus two unoperated, two sham-operated, two with silicons rubber casts placed at similar pressures, and four with casts placed at 95 mm Hg pressure were given a 2% cholesterol-enriched diet for 7 to 11 weeks, and then their arteries were examined. In all rabbits, atherosclerotic lesions developed at the origins of the Intercostal, cellac, superior mesenterlc, and both renal arteries, and at the aortic bifurcation, with these notable exceptions: no lesions developed at the origins of casted renal arteries or at the casted aortic bifurcations when the cast was placed at a low pressure. Measurements of the diameter and thickness of the aorta In the left renal branch and aortic bifurcation areas, with and without the casts, indicated that there was no significant narrowing of the aortic lumen or thinning of the aorta due to the cast In conclusion, the Inhibition of the development of atherosclerotic lesions appears to be associated with the reduction of arterial Intramural stress.

Study of stress concentration in the walls of the bovine coronary arterial branch

The intramural stress concentration in the arterial wall is studied at the bovine circumflex coronary arterial branch. The material properties, geometry, and strains in the arterial branch are determined from experiments. The stresses are determined using a finite element analysis. The arterial branch is modeled as two interesecting thin cylindrical shells incorporating local variations in the branch geometry, thickness, and material properties. The artery is considered orthotropic and loaded with an incremental pressure of 40 mmHg. The highest intramural stresses are found to be localized at the proximal and distal regions of the ostium and are not significantly affected by the elastic properties. The stresses are 3 to 4 times greater in the branch at the inner surface than in the straight segment. The strains are twice as large at the branch than in the straight segment. We speculate that this stress concentration could injure the artery and make the branch region susceptible to atherosclerosis.

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 cyclic changes and structure of the base of the aortic valve

Abstract The structure and behavior of the base of the aortic valve in the dogs were investigated. The structure was studied under light microscopy to determine the distribution of collagenous, elastic, and myocardial elements. The dimensional changes were studied in vivo, by attaching radio-paque markers to the base and observing their movement by x-ray studies. The base is partly composed of ventricular myocardium. Two of the three trigonal regions consist of myocardium, and the right and left coronary leaflets and sinuses are encompassed by ventricular myocardium. The collagenous tissue that lies internal to the myocardium is neither dense nor thick and does not form a complete ring. The cyclic dimensional changes in the base are similar to the cyclic changes in left ventricular geometry and volume. The base perimeter is maximal in early systole coincident with the “rounding” of the ventricular cavity during isovolumetric contraction. The base perimeter decreases during systole when the ventricular volume decreases during systolic ejection. The base perimeter increases during diastole as the ventricular volume increases due to diastolic filling. The amount of cyclic change in the base perimeter at normal systemic pressure was different for different dogs. In four dogs the amount of change varied from 5% to 28% over a wide range of systemic pressures. The importance of the behavior of the base in normal valvular function is discussed. It is speculated that the mismatch between the nonexpansile sewing ring of an aortic bioprosthesis and the normally expansile base of the valve could cause occasional periprosthetic leaks.

Normal aortic valve function in dogs

Abstract Previous trileaflet aortic prostheses failed from fatigue and flexion stresses because their design was not based on the physiology of the normal valve. The dynamics of normal aortic valves were studied in terms of movement of aortic valve commissures and leaflets in vivo. Eight dogs were placed on total cardiopulmonary bypass; through an aortotomy, radiopaque platinum markers were placed on the commissures at the level of leaflet coaptation and at the center of the leaflets free edge. Three dogs were studied immediately and five dogs after 10 or more days. Marker movement in the beating heart was recorded under fluoroscopy on videotape. The aortic root expands 12 ± 0.4 percent (mean ± standard error of the mean) during systole at a blood pressure of 12080mm Hg; it expands 8.5 to 24 percent at blood pressures ranging from 5030 to 240180 mm Hg. The relation between aortic root diameter and blood pressure is similar to a classic tension-radius relation of the aorta. The aortic root diameter is controlled by blood pressure and by the pressure gradient across the valve. The functional elastic modulus of the aortic root is 4.4 × 10 5 dynes/cm 2 . Expansion of the aortic root begins 20 to 40 msec before the valve opens. The velocity of leaflet opening is 97 cm/sec. The orifice of the opened valve is circular and maximal at the beginning, gradually decreasing to the point when the valve snaps shut. Commissural expansion gives a smooth opening, less shear stress on the leaflet surface, less flexion stress at the center of the leaflet and less fatigue strain on the leaflet, thereby maximizing the life and efficiency of the aortic valve. If these characteristics were incorporated into aortic prostheses, prosthetic failure due to fatigue and flexion stresses should be reduced.

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.

Change in endothelial cell morphology at arterial branch sites caused by a reduction of intramural stress

Arterial branch sites have very high intramural stresses at physiologic intraluminal pressures; the same sites have a predilection for atherosclerosis. The effect of intramural stress on endothelial cell morphology was investigated. Five rabbits had permanent casts placed around a segment of the abdominal aorta-left renal artery branch area during controlled hypotension, thus reducing intramural stress without narrowing the lumen. These five animals, and three normal rabbits, were sacrificed after 4-8 weeks, and the vessels were perfused with buffered 2.5% glutaraldehyde for 2 h at 100 mm Hg pressure. The aortas were examined by scanning electron microscopy. In normal aortas, the distal region of the ostia of the left renal and celiac arteries just beyond the flow divider displayed many morphologically altered endothelial cells ranging from spindle shape to cobble-stone shape. The same aortic area of casted rabbits, as well as the straight abdominal aorta in all rabbits, showed a smooth surface of endothelial cells with intact cell borders and no morphologically altered cells. At branch sites, the occurrence of morphologically altered endothelial cells may be due to increased intramural stress. When intramural stress is reduced, the morphology of branch endothelial cells changes to resemble that of the unbranched regions. In conclusion, endothelial cell morphology changes in response to changes in intramural stress.

Distribution of low density lipoprotein in the branch and non-branch regions of the aorta☆

Atherosclerosis occurs focally in branch segments of the artery. Understanding why these segments are more susceptible to the development of the disease is at the root of understanding atherogenesis. We investigated accumulation of low density lipoprotein (LDL) in the branch and non-branch regions of the aorta to determine why the disease develops in branch regions. Abdominal aortas and their major branches were harvested from 36 rabbits. Rabbit LDL was prepared from whole blood and radiolabeled with 125I. The aorta was incubated with radiolabeled LDL in the lumen at 37 degrees C, under intraluminal pressure of 2-3 mmHg, for 1 h. Disks of 1.8 mm diameter were punched from the branch and non-branch regions of the aorta, cryosectioned and the sections counted in a gamma counter. Protein bound radioactivity was determined by TCA precipitation. LDL accumulation was highest towards the aortic intima and declined sharply towards the media. LDL accumulation at any given depth was higher in the branch than non-branch region. LDL accumulation in the intimal-medial sections was 87% higher in the branch than non-branch region. Total LDL accumulation in the branch was almost twice that in the non-branch region. Mean LDL accumulation was also greater in the branch than non-branch region. The aorta was significantly thicker at the branch. LDL distribution profiles indicate that LDL is present in a greater concentration and over a greater depth in the branch than non-branch region. The tendency of the branch region to accumulate LDL in greater amounts may explain its susceptibility to atherosclerotic lesion development.