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J Appl Physiol 97: 984-990, 2004. First published May 7, 2004; doi:10.1152/japplphysiol.00162.2004
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Bionic epidural stimulation restores arterial pressure regulation during orthostasis

Yusuke Yanagiya,1,2 Takayuki Sato,1,3 Toru Kawada,1 Masashi Inagaki,1 Teiji Tatewaki,1,4 Can Zheng,1,2 Atsunori Kamiya,1 Hiroshi Takaki,1 Masaru Sugimachi,1 and Kenji Sunagawa1

1Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565; 2Pharmaceuticals and Medical Devices Agency, Chiyoda-ku, Tokyo 100-0013; 3Department of Cardiovascular Control, Kochi Medical School, Nankoku, Kochi 783-8505; and 4Japan Association for the Advancement of Medical Equipment, Bunkyo-ku, Tokyo 113-0033, Japan

Submitted 13 February 2004 ; accepted in final form 30 April 2004

A bionic baroreflex system (BBS) is a computer-assisted intelligent feedback system to control arterial pressure (AP) for the treatment of baroreflex failure. To apply this system clinically, an appropriate efferent neural (sympathetic vasomotor) interface has to be explored. We examined whether the spinal cord is a candidate site for such interface. In six anesthetized and baroreflex-deafferentiated cats, a multielectrode catheter was inserted into the epidural space to deliver epidural spinal cord stimulation (ESCS). Stepwise changes in ESCS rate revealed a linear correlation between ESCS rate and AP for ESCS rates of 2 pulses/s and above (r2, 0.876–0.979; slope, 14.3 ± 5.8 mmHg·pulses–1·s; pressure axis intercept, 35.7 ± 25.9 mmHg). Random changes in ESCS rate with a white noise sequence revealed dynamic transfer function of peripheral effectors. The transfer function resembled a second-order, low-pass filter with a lag time (gain, 16.7 ± 8.3 mmHg·pulses–1·s; natural frequency, 0.022 ± 0.007 Hz; damping coefficient, 2.40 ± 1.07; lag time, 1.06 ± 0.41 s). On the basis of the transfer function, we designed an artificial vasomotor center to attenuate hypotension. We evaluated the performance of the BBS against hypotension induced by 60° head-up tilt. In the cats with baroreflex failure, head-up tilt dropped AP by 37 ± 5 mmHg in 5 s and 59 ± 11 mmHg in 30 s. BBS with optimized feedback parameters attenuated hypotension to 21 ± 2 mmHg in 5 s (P < 0.05) and 8 ± 4 mmHg in 30 s (P < 0.05). These results indicate that ESCS-mediated BBS prevents orthostatic hypotension. Because epidural stimulation is a clinically feasible procedure, this BBS can be applied clinically to combat hypotension associated with various pathophysiologies.

baroreceptors; blood pressure; autonomic nervous system; Shy-Drager syndrome; orthostatic hypotension



Address for reprint requests and other correspondence: M. Sugimachi, Dept. of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita 565–8565, Japan.




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