Rickards CA, Ryan KL, Cooke WH, Lurie KG, Convertino VA. Inspiratory resistance delays the reporting of symptoms with central hypovolemia: association with cerebral blood flow. Am J Physiol Regul Integr Comp Physiol 293: R243-R250, 2007. First published May 16, 2007; doi:10.1152/ajpregu.00087.2007.-We tested the hypothesis that breathing through an inspiratory threshold device (ITD) during progressive central hypovolemia would protect cerebral perfusion and attenuate the reporting of presyncopal symptoms. Eight human subjects were exposed to lower-body negative pressure (LBNP) until the presence of symptoms while breathing through either an active ITD (Ϫ7 cmH2O impedance) or a sham ITD (0 cmH2O). Cerebral blood flow velocity (CBFV) was measured continuously via transcranial Doppler and analyzed in both time and frequency domains. Subjects were asked to report any subjective presyncopal symptoms (e.g., dizziness, nausea) at the conclusion of each LBNP exposure. Symptoms were coincident with physiological evidence of cardiovascular collapse (e.g., hypotension, bradycardia). Breathing on the active ITD increased LBNP tolerance time (mean Ϯ SE) from 2,014 Ϯ 106 s to 2,259 Ϯ 138 s (P ϭ 0.006). We compared CBFV responses at the time of symptoms during the sham ITD trial with those at the same absolute time during the active ITD trial (when there were no symptoms). While there was no difference in mean CBFV at these time points (sham, 44 Ϯ 4 cm/s vs. active, 47 Ϯ 4; P ϭ 0.587), total oscillations (sum of high-and low-frequency spectral power) of CBFV were higher (P ϭ 0.004) with the active ITD (45.6 Ϯ 10.2 cm/s 2 ) than the sham ITD (22.1 Ϯ 5.4 cm/s 2 ). We conclude that greater oscillations around the same absolute level of mean CBFV are induced by inspiratory resistance and may contribute to the delay in symptoms and cardiovascular collapse that accompany progressive central hypovolemia.inspiratory threshold device; cerebral blood flow regulation; lowerbody negative pressure THE PRESERVATION OF CEREBRAL blood flow during hypotensive stress is integral in delaying the onset of presyncopal symptoms and maintaining consciousness. Recent data reported from several investigations have demonstrated the benefits of an inspiratory impedance threshold device (ITD) in elevating cerebral perfusion pressure in animals (39, 40) and reducing the reporting of presyncopal symptoms in humans (8, 27) with reductions in central blood volume.The ITD was designed to create a greater reduction in intrathoracic pressure during inspiration, enhancing the natural vacuum within the chest (26, 37). This vacuum promotes an increase in venous return, thereby increasing ventricular preload and subsequent cardiac output (Q) and arterial blood pressure (9, 26). Breathing on the ITD also increases cerebral blood flow velocity (CBFV) in resting, supine humans (12) and in the hemorrhaging porcine model, application of negative intrathoracic pressure reduces intracranial pressure (ICP) and subsequently elevates cerebral perfusion pressure (40, 41). Th...