Stehbens William E
Department of Pathology, Wellington School of Medicine, Wellington, New Zealand.
Cardiovasc Pathol. 1997 May-Jun;6(3):123-53. doi: 10.1016/s1054-8807(96)00090-7.
The consistent topography, transmural involvement, and variation in severity and rate of progression in individual atherosclerotic lesions collectively indicate the dominant, primary role of hemodynamics. Specific anatomic configurations, vessels with elevated pressure, high velocity, or disturbed flow and iatrogenic production of accelerated atherosclerosis and its complications in therapeutic venous bypass grafts and arteriovenous shunts point to this role. The morphology and complications are consistent with the loss of cohesion and tensile strength of mural constituents and irreconcilably different from those of cholesterol- or fat-overfed animals and from other metabolic lipid storage disorders. These observations preclude dietary and circulating humoral factors and negate currently prevailing etiologic hypotheses that do not account for topography, pathogenesis, or complications. Atherosclerosis is the response to hemodynamically induced repetitive tensile stresses due to the pulse pressure and lesser flow-generated vibrations resulting in bioengineering fatigue occasioned by cumulative molecular fragmentation of mural constituents. This phenomenon also accounts for free-radical formation and lipoperoxidation. Atherosclerosis thus constitutes the combined manifestations of tissue fatigue and compensatory repair. When fatigue predominates, mural failure leads to the development of the primary complications (mural tears, dissection, ectasia, tortuosity, aneurysms). Lipid accumulation and thromboembolism are secondary phenomena. Fatigue onset is enhanced by hypertension and acquired or inherited defects of individual mural constituents. Iatrogenic and experimental production of atherosclerosis, its pathogenesis, and complications by hemodynamic means provides the ultimate proof of the causal role of bioengineering fatigue.
个体动脉粥样硬化病变中一致的形态、透壁累及情况以及严重程度和进展速度的差异共同表明了血流动力学的主导和主要作用。特定的解剖结构、压力升高、血流速度快或紊乱的血管，以及治疗性静脉搭桥移植和动静脉分流术中因医源性因素导致的动脉粥样硬化加速及其并发症，都指向了这一作用。其形态和并发症与壁成分凝聚力和抗张强度的丧失一致，与胆固醇或脂肪过量喂养动物以及其他代谢性脂质储存障碍的情况截然不同。这些观察结果排除了饮食和循环体液因素，并否定了目前流行的病因假说，这些假说无法解释病变的形态、发病机制或并发症。动脉粥样硬化是对由于脉压和较小的血流产生的振动所导致的血流动力学诱导的重复性拉伸应力的反应，这种应力会导致壁成分的累积分子碎片化，从而引发生物工程疲劳。这种现象也解释了自由基的形成和脂质过氧化。因此，动脉粥样硬化构成了组织疲劳和代偿性修复的综合表现。当疲劳占主导时，壁衰竭会导致主要并发症（壁撕裂、夹层、扩张、迂曲、动脉瘤）的发生。脂质积聚和血栓栓塞是继发现象。高血压以及个体壁成分的后天或遗传缺陷会加剧疲劳的发生。通过血流动力学手段医源性和实验性地产生动脉粥样硬化、其发病机制和并发症，为生物工程疲劳的因果作用提供了最终证据。
