Bicuspid aortic valves undergo excessive strain during opening: a simulation study.

OBJECTIVE: The objective of this study was to examine the influence of the morphologic characteristics of the bicuspid aortic valve on its disease progression by comparing the motion, stress/strain distribution, and blood flow of normal and stenotic tricuspid valves using simulation models. METHODS: Bicuspid, stenotic tricuspid with commissural fusion or thickened leaflet, and normal aortic valves were modeled with internal blood flow. Blood flow and the motion of aortic valve leaflets were studied using fluid-structure interaction finite element analysis, and stress/strain (curvature) distributions were calculated during the cardiac cycle. To mimic disease progression, we modified the local thickness of the leaflet where the bending stress was above a threshold. RESULTS: Transvalvular pressure gradient was greater in the bicuspid valve compared with the stenotic tricuspid valve with a similar valvular area. The bending strain (curvature) increased in both stenotic tricuspid and bicuspid valves, but a greater increase was observed in the bicuspid valve, and this was concentrated on the midline of the fused leaflets. During disease progression analysis, severity of the stenosis increased only in the bicuspid aortic valve model in terms of valvular area and pressure gradient. CONCLUSIONS: The characteristic morphology of the bicuspid valve creates excessive bending strain on the leaflets during ventricular ejection. Such mechanical stress may be responsible for the rapid progression of this disease.

The sinus of Valsalva relieves abnormal stress on aortic valve leaflets by facilitating smooth closure.

OBJECTIVE: Recently, various modifications have been made to aortic root replacement procedures to include the pseudosinus in the synthetic graft, but its effect on valve function still remains to be elucidated. The purpose of this study was to compare the flow dynamics and its influence on the stress/strain in the valve leaflet in two types of aortic root, either with or without the pseudosinus, with a simulation model. METHODS: The proximal portions of the ascending aorta and aortic valves were modeled with blood flowing inside. Blood flow and the motion of aortic valve leaflets were studied while applying a physiologic pressure waveform using fluid-structure interaction finite element analysis. Waveforms were varied to simulate the change in cardiac contractility. RESULTS: In the aorta without the sinus, the time during which the valve was open was longer and the rapid valve closing velocity was faster under all conditions studied. In the pseudosinus model, we could clearly observe vortex formation from the early phase of ejection, which seemed to facilitate the gradual but smooth closure of the valve. Valve leaflets without the sinus were subject to greater stress and underwent bending deformation in the longitudinal direction. CONCLUSIONS: Sinuses of Valsalva facilitate the smooth closure of the aortic valve, thereby avoiding the building up of abnormal stress in the leaflet. Such an effect may assure the durability of valve leaflets in aortic grafts with a pseudosinus.

Relationship between prostatic alpha(1)-adrenoceptor binding and reduction in intraurethral pressure following continuous infusion of KMD-3213 in rats.

The relationship between alpha(1)-adrenoceptor binding in rat tissues and pharmacodynamic effects of continuous infusion of KMD-3213 was examined. In vivo specific binding of [(3)H]KMD-3213 after continuous intravenous infusion of the ligand (100 pmol/kg/min for 10 min, followed by 30 pmol/kg/min for 60 or 90 min) differed largely among the tissues examined. Specific binding of [(3)H]KMD-3213 in aorta, heart, lung, and kidney was not different in terms of infusion time in the case of continuous infusion for 10, 70 and 100 min, whereas the binding in prostate, vas deferens, and submaxillary gland by 70- and/or 100-min infusion was significantly greater than that by the 10-min infusion. A similar extent of specific binding in the prostate was observed by the infusion (100 min) of a three-fold higher dose of [(3)H]KMD- 3213. Continuous intravenous infusion of KMD-3213 (100 pmol/kg/min for 10 min, followed by 30 pmol/kg/min) for 70 or 100 min significantly reduced the phenylephrine-induced increase in the mean blood pressure and that in the intraurethral pressure of anesthetized rats. Extent and time course of the KMD-3213 effect reduction in the phenylephrine-induced increase in intraurethral pressure were closely associated with those in prostatic [(3)H]KMD-3213 binding after continuous infusion of the corresponding dosage of the radioligand. The reduction in the phenylephrine-induced increase by the infusion of a three-fold higher dose of KMD-3213 was significantly greater in the case of the intraurethral pressure than in that of the mean blood pressure, thereby suggesting a greater selectivity for the alpha(1)-adrenoceptor in the lower urinary tract than for that in the vascular tissue. In conclusion, the present study has shown that specific binding of [(3)H]KMD-3213 in the rat prostate after the continuous intravenous infusion of the radioligand may be closely associated with the pharmacological effect of this drug on the lower urinary tract.