Department of Mechanical Engineering, University of Louisville, Louisville, KY 20299, USA
Eur J Clin Invest. 2011 Aug;41(8):807-19. doi: 10.1111/j.1365-2362.2010.02466.x. Epub 2011 Jan 31.
Of the many possible factors that may contribute to orthostatic intolerance, the loss of circulating blood because of capillary filtration is one of the few that can explain the gradual decline of arterial pressure during stand tests. This study used a computer model to investigate the relative importance of haemodynamic parameters, including capillary filtration, as potential contributors to orthostatic intolerance. Simulated orthostatic tolerance times were compared to previous experiments combining head-up tilt and lower body negative pressure graded orthostatic stress, which provided haemodynamic data, in particular haematocrit measurements that allowed subject-specific modelling of capillary transport.
The cardiovascular system was simulated using a seven-compartment model with measured heart rate, stroke volume, total peripheral resistance, mean arterial pressure and haematocrit data for 12 subjects. Simulations were controlled by decreasing the total blood volume at the measured rates of capillary filtration until cerebral pressure dropped below a threshold for consciousness. Predicted times to syncope were compared to actual times to presyncope, and sensitivity of arterial pressure and cardiac output to independent system parameters were determined.
There was no statistical difference in modelled times to syncope and actual times to presyncope. Both arterial pressure and cardiac output were most sensitive to total blood volume and least sensitive to caudal compliance parameters.
The feasibility of subject-specific simulations of cardiovascular response to orthostatic stress was demonstrated, providing stronger evidence that capillary filtration is a prominent mechanism in causing orthostatic intolerance. These results may have clinical and spaceflight applications.
在导致直立不耐受的众多可能因素中,由于毛细血管滤过而导致的循环血量损失是少数几个可以解释直立试验期间动脉压逐渐下降的因素之一。本研究使用计算机模型来研究血液动力学参数(包括毛细血管滤过)作为潜在的直立不耐受因素的相对重要性。模拟的直立耐受时间与之前的实验进行了比较,该实验将头高位倾斜和下体负压分级直立应激相结合,提供了血液动力学数据,特别是血细胞比容测量值,允许对毛细血管转运进行特定于个体的建模。
使用具有测量心率、每搏量、总外周阻力、平均动脉压和 12 名受试者血细胞比容数据的七腔室模型模拟心血管系统。通过以测量的毛细血管滤过率降低总血容量来控制模拟,直到脑压降至意识阈值以下。将预测的晕厥时间与实际的晕厥前时间进行比较,并确定动脉压和心输出量对独立系统参数的敏感性。
模拟的晕厥时间与实际的晕厥前时间没有统计学差异。动脉压和心输出量对总血容量最敏感,对尾部顺应性参数最不敏感。
证明了对直立应激心血管反应进行特定于个体的模拟的可行性,为毛细血管滤过是导致直立不耐受的主要机制提供了更强有力的证据。这些结果可能具有临床和太空飞行应用价值。