Background and Purpose-The relationship between middle cerebral artery (MCA) flow velocity (CFV) and cerebral blood flow (CBF) is uncertain because of unknown vessel diameter response to physiological stimuli. The purpose of this study was to directly examine the effect of a simulated orthostatic stress (lower body negative pressure [LBNP]) as well as increased or decreased end-tidal carbon dioxide partial pressure (P ET CO 2 ) on MCA diameter and CFV. Methods-Twelve subjects participated in a CO 2 manipulation protocol and/or an LBNP protocol. In the CO 2 manipulation protocol, subjects breathed room air (normocapnia) or 6% inspired CO 2 (hypercapnia), or they hyperventilated to Ϸ25 mm Hg P ET CO 2 (hypocapnia). In the LBNP protocol, subjects experienced 10 minutes each of Ϫ20 and Ϫ40 mm Hg lower body suction. CFV and diameter of the MCA were measured by transcranial Doppler and MRI, respectively, during the experimental protocols. Results-Compared with normocapnia, hypercapnia produced increases in both P ET CO 2 (from 36Ϯ3 to 40Ϯ4 mm Hg, PϽ0.05) and CFV (from 63Ϯ4 to 80Ϯ6 cm/s, PϽ0.001) but did not change MCA diameters (from 2.9Ϯ0.3 to 2.8Ϯ0.3 mm). Hypocapnia produced decreases in both P ET CO 2 (24Ϯ2 mm Hg, PϽ0.005) and CFV (43Ϯ7 cm/s, PϽ0.001) compared with normocapnia, with no change in MCA diameters (from 2.9Ϯ0.3 to 2.9Ϯ0.4 mm). During Ϫ40 mm Hg LBNP, P ET CO 2 was not changed, but CFV (55Ϯ4 cm/s) was reduced from baseline (58Ϯ4 cm/s, PϽ0.05), with no change in MCA diameter. Conclusions-Under the conditions of this study, changes in MCA diameter were not detected. Therefore, we conclude that relative changes in CFV were representative of changes in CBF during the physiological stimuli of moderate LBNP or changes in P ET CO 2 .

To establish the accuracy of transcranial Doppler ultrasound (TCD) measures of middle cerebral artery (MCA) cerebral blood flow velocity (CBFV) as a surrogate of cerebral blood flow (CBF) during hypercapnia (HC) and hypocapnia (HO), we examined whether the cross-sectional area (CSA) of the MCA changed during HC or HO and whether TCD-based estimates of CBFV were equivalent to estimates from phase contrast (PC) magnetic resonance imaging. MCA CSA was measured from 3T magnetic resonance images during baseline, HO (hyperventilation at 30 breaths/min), and HC (6% carbon dioxide). PC and TCD measures of CBFV were measured during these protocols on separate days. CSA and TCD CBFV were used to calculate CBF. During HC, CSA increased from 5.6 ± 0.8 to 6.5 ± 1.0 mm(2) (P < 0.001, n = 13), while end-tidal carbon dioxide partial pressure (PETCO2) increased from 37 ± 3 to 46 ± 5 Torr (P < 0.001). During HO, CSA decreased from 5.8 ± 0.9 to 5.3 ± 0.9 mm(2) (P < 0.001, n = 15), while PetCO2 decreased from 36 ± 4 to 23 ± 3 Torr (P < 0.001). CBFVs during baseline, HO, and HC were compared between PC and TCD, and the intraclass correlation coefficient was 0.83 (P < 0.001). The relative increase from baseline was 18 ± 8% greater (P < 0.001) for CBF than TCD CBFV during HC, and the relative decrease of CBF during HO was 7 ± 4% greater than the change in TCD CBFV (P < 0.001). These findings challenge the assumption that the CSA of the MCA does not change over modest changes in PETCO2.

No abstract

No abstract

The purpose of the present study was to determine the cortical structures involved with integrated baroreceptor-mediated modulation of autonomic cardiovascular function in conscious humans independent of changes in arterial blood pressure. We assessed the brain regions associated with lower body negative pressure (LBNP)-induced baroreflex control using functional magnetic resonance imaging with blood oxygen level-dependent (BOLD) contrast in eight healthy male volunteer subjects. The levels of LBNP administered were 5, 15 and 35 mmHg. Heart rate (HR; representing the cardiovascular response) and LBNP (representing the baroreceptor activation level) were simultaneously monitored during the scanning period. In addition, estimated central venous pressure (CVP), arterial blood pressure (ABP) and muscle sympathetic nerve activity were recorded on a separate session. Random effects analyses (SPM2) were used to evaluate significant (P < 0.05) BOLD signal changes that correlated separately with both LBNP and HR (15-and 35-mmHg versus 5-mmHg LBNP). Compared to baseline, steady-state LBNP at 15 and 35 mmHg decreased CVP (from 7 ± 1 to 5 ± 1 and 4 ± 1 mmHg, respectively) and increased MSNA (from 12 ± 1 to 23 ± 3 and 36 ± 4 bursts min −1 , respectively, both P < 0.05 versus baseline). Furthermore, steady-state LBNP elevated HR from 54 ± 2 beats min −1 at baseline to 64 ± 2 beats min −1 at 35-mmHg suction. Both mean arterial and pulse pressure were not different between rest and any level of LBNP. Cortical regions demonstrating increased activity that correlated with higher HR and greater LBNP included the right superior posterior insula, frontoparietal cortex and the left cerebellum. Conversely, using the identical statistical paradigm, bilateral anterior insular cortices, the right anterior cingulate, orbitofrontal cortex, amygdala, midbrain and mediodorsal nucleus of the thalamus showed decreased neural activation. These data corroborate previous investigations highlighting the involved roles of the insula, anterior cingulate cortex and amygdala in central autonomic cardiovascular control. In addition, we have provided the first evidence for the identification of the cortical network involved specifically with baroreflex-mediated autonomic cardiovascular function in conscious humans.

The hypothesis that the rate of increase in muscle O2 uptake (VO2mus) at the onset of exercise is influenced by muscle blood flow was tested during forearm exercise with the arm either above or below heart level to modify perfusion pressure. Ten young men exercised at a power of approximately 2.2 W, and five of these subjects also worked at 1.4 W. Blood flow to the forearm was calculated from the product of blood velocity and cross-sectional area obtained with Doppler techniques. Venous blood was sampled from a deep forearm vein to determine O2 extraction. The rate of increase in VO2mus and blood flow was assessed from the mean response time (MRT), which is the time to achieve approximately 63% increase from baseline to steady state. In the arm below heart position during the 2.2-W exercise, blood flow and VO2mus both increased, with a MRT of approximately 30 s. With the arm above the heart at this power, the MRTs for blood flow [79.8 +/- 15.7 (SE)s] and VO2mus (50.2 +/- 4.0 s) were both significantly slower. Consistent with these findings were the greater increases in venous plasma lactate concentration over resting valued in the above heart position (2.8 +/- 0.4 mmol/l) than in the below heart position (0.9 +/- mmol/l). At the lower power, both blood flow and VO2mus also increased more rapidly with the arm below compared with above the heart. These data support the hypothesis that changes in blood flow at the onset of exercise have a direct effect on oxidative metabolism through alterations in O2 transport.

Removal of the normal head-to-foot gravity vector and chronic weightlessness during spaceflight might induce cardiovascular and metabolic adaptations related to changes in arterial pressure and reduction in physical activity. We tested hypotheses that stiffness of arteries located above the heart would be increased postflight, and that blood biomarkers inflight would be consistent with changes in vascular function. Possible sex differences in responses were explored in four male and four female astronauts who lived on the International Space Station for 6 mo. Carotid artery distensibility coefficient (P = 0.005) and β-stiffness index (P = 0.006) reflected 17-30% increases in arterial stiffness when measured within 38 h of return to Earth compared with preflight. Spaceflight-by-sex interaction effects were found with greater changes in β-stiffness index in women (P = 0.017), but greater changes in pulse wave transit time in men (P = 0.006). Several blood biomarkers were changed from preflight to inflight, including an increase in an index of insulin resistance (P< 0.001) with a spaceflight-by-sex term suggesting greater change in men (P = 0.034). Spaceflight-by-sex interactions for renin (P = 0.016) and aldosterone (P = 0.010) indicated greater increases in women than men. Six-month spaceflight caused increased arterial stiffness. Altered hydrostatic arterial pressure gradients as well as changes in insulin resistance and other biomarkers might have contributed to alterations in arterial properties, including sex differences between male and female astronauts.

(SD 4)] performed repetitions (6 -8) of twolegged, moderate-intensity, knee-extension exercise during two separate protocols that included step transitions from 3 W to 90% estimated lactate threshold ( L) performed as a single step (S3) and in two equal steps (S1, 3 W to ϳ45% L; S2, ϳ45% L to ϳ90% L). The time constants ( ) of pulmonary oxygen uptake (V O2), leg blood flow (LBF), heart rate (HR), and muscle deoxygenation (HHb) were greater (P Ͻ 0.05) in S2 ( V O2, ϳ52 s; LBF, ϳ 39 s; HR, ϳ42 s; HHb, ϳ33 s) compared with S1 ( V O2, ϳ24 s; LBF, ϳ21 s; HR, ϳ21 s; HHb, ϳ16 s), while the delay before an increase in HHb was reduced (P Ͻ 0.05) in S2 (ϳ14 s) compared with S1 (ϳ20 s). The V O2 and HHb amplitudes were greater (P Ͻ 0.05) in S2 compared with S1, whereas the LBF amplitude was similar in S2 and S1. Thus the slowed V O2 response in S2 compared with S1 is consistent with a mechanism whereby V O2 kinetics is limited, in part, by a slowed adaptation of blood flow and/or O2 transport when exercise was initiated from a baseline of moderate-intensity exercise.oxygen uptake kinetics; femoral arterial blood flow kinetics; Doppler ultrasound; knee-extension exercise; near-infrared spectroscopy ACCOMPANYING A RISE IN EXERCISE intensity, there is a challenge to increase the rate of oxidative phosphorylation to meet the new metabolic demand of the working muscle. To meet this demand, the respiratory and cardiovascular systems must adapt in a coordinated manner to transport O 2 from the atmosphere to the mitochondria of the exercising muscle, thus allowing oxidative phosphorylation to proceed at the required rate. Pulmonary O 2 uptake (V O 2 ) kinetics is an index of the overall efficiency and conditioning of these integrated systems and can provide pertinent information with regard to the various mechanisms regulating O 2 delivery and O 2 utilization by skeletal muscle during exercise.Recently, it was reported (8) that, for a given absolute increase in work rate (WR), the adaptation of V O 2 during leg-cycling exercise was slower and the gain (G) (i.e., ⌬V O 2 / ⌬WR) was greater when exercise was initiated in the upper compared with the lower regions of the moderate-intensity exercise domain. These observations agree with those of Hughson and Morrissey (22,23) and DiPrampero et al. (13), but differ from those of DiPrampero et al. (12) and Diamond et al.(10), who reported either a faster or similar adaptation, respectively, when comparing exercise initiated from either prior moderate-intensity exercise or rest.Brittain et al. (8) attributed the slowing of V O 2 kinetics in the upper region of the moderate-intensity domain to the bioenergetic properties of the newly recruited motor units, which were assumed to be less efficient (i.e., greater O 2 or ATP cost per contraction) with a more slowly adapting V O 2 response than those motor units recruited initially at exercise onset from rest or very light exercise (i.e., lower region of the moderateintensity domain). Hughson and Morrissey (22,23), however, suggested that the sl...