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Am J Physiol Regul Integr Comp Physiol 291: R1355-R1368, 2006. First published June 22, 2006; doi:10.1152/ajpregu.00205.2006
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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Modeling baroreflex regulation of heart rate during orthostatic stress

Mette S. Olufsen,1 Hien T. Tran,1 Johnny T. Ottesen,2 Research Experiences for Undergraduates Program1 Lewis A. Lipsitz,3,4,5 Vera Novak4,5

1Department of Mathematics, North Carolina State University, Raleigh, North Carolina; 2Department of Mathematics and Physics, Roskilde University, Roskilde, Denmark; 3Institute for Aging Research, Hebrew Senior Life, Boston, Massachusetts; 4Division of Gerontology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and 5Harvard Medical School, Boston, Massachusetts

Submitted 21 March 2006 ; accepted in final form 27 May 2006

During orthostatic stress, arterial and cardiopulmonary baroreflexes play a key role in maintaining arterial pressure by regulating heart rate. This study presents a mathematical model that can predict the dynamics of heart rate regulation in response to postural change from sitting to standing. The model uses blood pressure measured in the finger as an input to model heart rate dynamics in response to changes in baroreceptor nerve firing rate, sympathetic and parasympathetic responses, vestibulo-sympathetic reflex, and concentrations of norepinephrine and acetylcholine. We formulate an inverse least squares problem for parameter estimation and successfully demonstrate that our mathematical model can accurately predict heart rate dynamics observed in data obtained from healthy young, healthy elderly, and hypertensive elderly subjects. One of our key findings indicates that, to successfully validate our model against clinical data, it is necessary to include the vestibulo-sympathetic reflex. Furthermore, our model reveals that the transfer between the nerve firing and blood pressure is nonlinear and follows a hysteresis curve. In healthy young people, the hysteresis loop is wide, whereas, in healthy and hypertensive elderly people, the hysteresis loop shifts to higher blood pressure values, and its area is diminished. Finally, for hypertensive elderly people, the hysteresis loop is generally not closed, indicating that, during postural change from sitting to standing, baroreflex modulation does not return to steady state during the first minute of standing.

mathematical modeling; heart rate control; baroreflex function; sympathetic and parasympathetic responses; vestibulo-sympathetic reflex


Address for reprint requests and other correspondence: M. Olufsen, Dept. of Mathematics, North Carolina State Univ., Campus Box 8205, Raleigh, NC 27695 (e-mail: msolufse{at}math.ncsu.edu)






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