PII S0361-9230(00)00315-4 Cerebral vasoconstriction precedes orthostatic intolerance after parabolic flight J. M. Serrador, 1 J. K. Shoemaker, 1 * T. E. Brown, 2 M. S. Kassam, 3 R. L. Bondar 3 and T. T. Schlegel 4 1 Neurovascular Research Lab, School of Kinesiology, The University of Western Ontario, London, Ontario, Canada; 2 Wyle Laboratories, Houston, TX, USA; 3 Faculty of Applied Science and Engineering, Ryerson Polytechnic University, Toronto, Ontario, Canada; and 4 Life Sciences Research Laboratories, National Aeronautics and Space Administration, Johnson Space Center, Houston, TX, USA [Received 24 April 2000; Accepted 15 May 2000] ABSTRACT: The effects of brief but repeated bouts of micro- and hypergravity on cerebrovascular responses to head-up tilt (HUT) were examined in 13 individuals after (compared to be- fore) parabolic flight. Middle cerebral artery mean flow velocity (MCA MFV; transcranial Doppler ultrasound), eye level blood pressure (BP) and end tidal CO 2 (P ET CO 2 ) were measured while supine and during 80° HUT for 30 min or until presyncope. In the postflight tests subjects were classified as being orthostatically tolerant (OT) (n  7) or intolerant (OI) (n  6). BP was diminished with HUT in the OT group in both tests (p < 0.05) whereas postflight BP was not different from supine in the OI group. Postflight compared to preflight, the reduction in P ET CO 2 with HUT (p < 0.05) increased in both groups, although significantly so only in the OI group (p < 0.05). The OI group also had a significant decrease in supine MCA MFV postflight (p < 0.05) that was unaccompanied by a change in supine P ET CO 2 . The decrease in MCA MFV that occurred during HUT in both groups preflight (p < 0.05) was accentuated only in the OI group post- flight, particularly during the final 30 s of HUT (p < 0.05). How- ever, this accentuated decrease in MCA MFV was not corre- lated to the greater decrease in P ET CO 2 during the same period (R  0.20, p  0.42). Although cerebral vascular resistance (CVR) also increased in the OI group during the last 30 s of HUT postflight (p < 0.05), the dynamic autoregulatory gain was not simultaneously changed. Therefore, we conclude that in the OI individuals, parabolic flight was associated with cerebral hypo- perfusion following a paradoxical augmentation of CVR by a mechanism that was not related to changes in autoregulation nor strictly to changes in P ET CO 2 . © 2000 Elsevier Science Inc. KEY WORDS: Transcranial Doppler, Middle cerebral artery, Mi- crogravity, Head-up tilt. INTRODUCTION Exposure to both real [4,9] and simulated [30,32] microgravity leads to an increased incidence of orthostatic intolerance (OI). This increased incidence of OI occurs regardless of whether the expo- sure to microgravity is prolonged [4] or brief [5]. Recently, an increased incidence of OI following repeated exposures to brief periods of micro- and hypergravity produced by parabolic flight has been reported [27]. OI is critically dependent upon adequate cerebral perfusion. In turn, cerebral perfusion is modulated by metabolic (CO 2 ), neuro- humoral and mechanical stimuli. However, very little is presently known about how exposure to microgravity affects cerebrovascu- lar responses to any of these stimuli. Of the various modulators of cerebral blood vessel tone, cerebral autoregulatory responses rep- resent an important and rapid mechanism to counter the reduction in cerebral perfusion pressure on moving from supine to the upright posture [2,13,21]. Thus, after exposure to microgravity, any impairment of cerebral autoregulation might predispose indi- viduals to OI [17]. Postural reductions in middle cerebral artery mean flow velocity (MCA MFV) following parabolic flight have been reported that were not associated with hypotension [27]. These data are reminiscent of those published by Bondar et al. [3] wherein reductions in MCA MFV were observed during lower body negative pressure (LBNP) in presyncopal individuals without concurrent hypotension. Bondar et al. [3] have hypothesized that during presyncopal LBNP tests, the curve representing the auto- regulatory range of cerebral blood flow control is shifted down- ward such that cerebral autoregulation is normal but operating at a reduced absolute level of cerebral blood flow (Fig. 1). In contrast, Zhang et al. [35] have found decreased MCA MFV during presyn- copal LBNP tests in conjunction with diminished dynamic auto- regulatory responses, hypothesizing with Levine et al. [17] an alternative rightward shift in the static cerebral autoregulatory curve. To determine whether impaired cerebral autoregulation con- tributes to the development of OI in humans after brief but re- peated exposures to micro- and hypergravity, we examined dy- namic cerebral autoregulatory responses to head up tilt (HUT) both before and after 2-h parabolic flights. Pre- and postparabolic flight cerebrovascular and hemodynamic responses to HUT were ob- tained as part of a larger, collaborative study [27]. We hypothe- sized that subjects who developed OI after parabolic flight would demonstrate greater decreases in MFV and increases in cerebral vascular resistance (CVR) without impairment of dynamic auto- regulation. * Address for correspondence: J. Kevin Shoemaker, Ph.D., Neurovascular Research Laboratory, School of Kinesiology, Room 3110, Thames Hall, University of Western Ontario, London, Ontario, Canada N6A 3K7; Fax: +1-(519)-661-2008; E-mail: kshoemak@julian.uwo.ca Brain Research Bulletin, Vol. 53, No. 1, pp. 113–120, 2000 Copyright © 2000 Elsevier Science Inc. Printed in the USA. All rights reserved 0361-9230/00/$–see front matter 113