Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, California, United States.
Laboratoire de Mécanique Paris-Saclay, Université Paris-Saclay, Paris, France.
Am J Physiol Heart Circ Physiol. 2023 Nov 1;325(5):H1193-H1209. doi: 10.1152/ajpheart.00314.2023. Epub 2023 Sep 15.
Age-related changes in aortic biomechanics can impact the brain by reducing blood flow and increasing pulsatile energy transmission. Clinical studies have shown that impaired cardiac function in patients with heart failure is associated with cognitive impairment. Although previous studies have attempted to elucidate the complex relationship between age-associated aortic stiffening and pulsatility transmission to the cerebral network, they have not adequately addressed the effect of interactions between aortic stiffness and left ventricle (LV) contractility (neither on energy transmission nor on brain perfusion). In this study, we use a well-established and validated one-dimensional blood flow and pulse wave computational model of the circulatory system to address how age-related changes in cardiac function and vasculature affect the underlying mechanisms involved in the LV-aorta-brain hemodynamic coupling. Our results reveal how LV contractility affects pulsatile energy transmission to the brain, even with preserved cardiac output. Our model demonstrates the existence of an optimal heart rate (near the normal human heart rate) that minimizes pulsatile energy transmission to the brain at different contractility levels. Our findings further suggest that the reduction in cerebral blood flow at low levels of LV contractility is more prominent in the setting of age-related aortic stiffening. Maintaining optimal blood flow to the brain requires either an increase in contractility or an increase in heart rate. The former consistently leads to higher pulsatile power transmission, and the latter can either increase or decrease subsequent pulsatile power transmission to the brain. We investigated the impact of major aging mechanisms of the arterial system and cardiac function on brain hemodynamics. Our findings suggest that aging has a significant impact on heart-aorta-brain coupling through changes in both arterial stiffening and left ventricle (LV) contractility. Understanding the underlying physical mechanisms involved here can potentially be a key step for developing more effective therapeutic strategies that can mitigate the contributions of abnormal LV-arterial coupling toward neurodegenerative diseases and dementia.
年龄相关的主动脉生物力学变化可通过减少血流和增加脉动能量传递来影响大脑。临床研究表明，心力衰竭患者的心脏功能受损与认知障碍有关。虽然先前的研究试图阐明与年龄相关的主动脉僵硬和脉动向大脑网络的传递之间的复杂关系，但它们没有充分考虑主动脉僵硬和左心室 (LV) 收缩性之间的相互作用的影响（无论是在能量传递还是在脑灌注方面）。在这项研究中，我们使用了一个经过充分验证的一维血流和脉搏波计算模型来研究心脏功能和脉管系统的年龄相关变化如何影响 LV-主动脉-大脑血流动力学耦合的潜在机制。我们的研究结果揭示了 LV 收缩性如何影响脉动能量向大脑的传递，即使心输出量保持不变。我们的模型表明，在不同的收缩性水平下，存在一个最佳心率（接近正常人的心率），可以使脉动能量向大脑的传递最小化。我们的研究结果还表明，在与年龄相关的主动脉僵硬的情况下，LV 收缩性降低会导致大脑血流减少更为明显。保持大脑的最佳血流需要增加收缩性或增加心率。前者始终会导致更高的脉动功率传递，而后者可以增加或减少随后向大脑传递的脉动功率。我们研究了动脉系统和心脏功能的主要衰老机制对脑血流动力学的影响。我们的研究结果表明，通过动脉僵硬和左心室 (LV) 收缩性的变化，衰老对心脏-主动脉-大脑耦联有重大影响。了解这里涉及的潜在物理机制可能是开发更有效的治疗策略的关键步骤，这些策略可以减轻异常 LV-动脉耦联对神经退行性疾病和痴呆的贡献。
