Modelling of cardiovascular response to graded orthostatic stress: role of capillary filtration

Abstract

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.