O'Rourke Michael F, Hashimoto Junichiro
St. Vincent's Clinic/University of New South Wales, Sydney, Australia.
J Am Coll Cardiol. 2007 Jul 3;50(1):1-13. doi: 10.1016/j.jacc.2006.12.050. Epub 2007 Jun 18.
The human arterial system in youth is beautifully designed for its role of receiving spurts of blood from the left ventricle and distributing this as steady flow through peripheral capillaries. Central to such design is "tuning" of the heart to arterial tree; this minimizes aortic pressure fluctuations and confines flow pulsations to the larger arteries. With aging, repetitive pulsations (some 30 million/year) cause fatigue and fracture of elastin lamellae of central arteries, causing them to stiffen (and dilate), so that reflections return earlier to the heart; in consequence, aortic systolic pressure rises, diastolic pressure falls, and pulsations of flow extend further into smaller vessels of vasodilated organs (notably the brain and kidney). Stiffening leads to increased left ventricular (LV) load with hypertrophy, decreased capacity for myocardial perfusion, and increased stresses on small arterial vessels, particularly of brain and kidney. Clinical manifestations are a result of diastolic LV dysfunction with dyspnea, predisposition to angina, and heart failure, and small vessel degeneration in brain and kidney with intellectual deterioration and renal failure. While aortic stiffening is the principal cause of cardiovascular disease with age in persons who escape atherosclerotic complications, it is not a specific target for therapy. The principal target is the smooth muscle in distributing arteries, whose relaxation has little effect on peripheral resistance but causes substantial reduction in the magnitude of wave reflection. Such relaxation is achieved through regular exercise and with the vasodilating drugs that are used in modern treatment of hypertension and cardiac failure.
年轻人的人体动脉系统设计精妙，能够接收来自左心室的一股股血液，并将其作为稳定的血流通过外周毛细血管进行分配。这种设计的核心是心脏与动脉树的“调谐”；这能使主动脉压力波动最小化，并将血流脉动限制在较大的动脉中。随着年龄增长，重复性脉动（约每年3000万次）会导致中心动脉弹性蛋白薄片疲劳和断裂，使其变硬（并扩张），从而使反射更早返回心脏；结果，主动脉收缩压升高，舒张压降低，血流脉动进一步扩展到血管扩张器官的较小血管（尤其是大脑和肾脏）。动脉僵硬会导致左心室（LV）负荷增加并伴有肥厚，心肌灌注能力下降，以及小动脉血管（尤其是大脑和肾脏的小动脉血管）压力增加。临床表现是舒张期左心室功能障碍导致呼吸困难、易患心绞痛和心力衰竭，以及大脑和肾脏的小血管退化导致智力衰退和肾衰竭。虽然在没有发生动脉粥样硬化并发症的人群中，主动脉僵硬是随年龄增长导致心血管疾病的主要原因，但它并非治疗的特定靶点。主要靶点是分布动脉中的平滑肌，其舒张对外周阻力影响不大，但能大幅降低波反射的幅度。通过规律运动以及现代治疗高血压和心力衰竭时使用的血管舒张药物可实现这种舒张。
