Inhibition of nitric oxide synthase does not alter dynamic cerebral autoregulation in humans

The aim of this study was to determine whether inhibition of nitric oxide synthase (NOS) alters dynamic cerebral autoregulation in humans. Beat-to-beat blood pressure (BP) and cerebral blood flow (CBF) velocity (transcranial Doppler) were measured in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). NOS was inhibited by intravenous NG-monomethyl-L-arginine (L-NMMA) infusion. Dynamic cerebral autoregulation was quantified by transfer function analysis of beat-to-beat changes in BP and CBF velocity. Pressor effects of L-NMMA on cerebral hemodynamics were compared with those of phenylephrine infusion. In the supine position, L-NMMA increased mean BP from 83+/-3 to 94+/-3 mmHg (P < 0.01). However, CBF velocity remained unchanged. Consequently, cerebrovascular resistance index (CVRI) increased by 15% (P < 0.05). BP and CBF velocity variability and transfer function gain at the low frequencies of 0.07-0.20 Hz did not change with L-NMMA infusion. Similar changes in mean BP, CBF velocity, and CVRI were observed after phenylephrine infusion, suggesting that increase in CVRI after L-NMMA was mediated myogenically by increase in arterial pressure rather than a direct effect of cerebrovascular NOS inhibition. During baseline tilt without L-NMMA, steady-state BP increased and CBF velocity decreased. BP and CBF velocity variability at low frequencies increased in parallel by 277% and 217%, respectively (P < 0.05). However, transfer function gain remained unchanged. During tilt with L-NMMA, changes in steady-state hemodynamics and BP and CBF velocity variability as well as transfer gain and phase were similar to those without L-NMMA. These data suggest that inhibition of tonic production of NO does not appear to alter dynamic cerebral autoregulation in humans.     

Dynamic cerebral autoregulation is preserved in neurally mediated syncope.

To test whether cerebral autoregulation is impaired in patients with neurally mediated syncope (NMS), we evaluated 15 normal subjects and 37 patients with recurrent NMS. Blood pressure (BP), heart rate, and cerebral blood velocity (CBV) (transcranial Doppler) were recorded at rest and during 80 degrees head-up tilt (HUT). Static cerebral autoregulation as assessed from the change in cerebrovascular resistance during HUT was the same in NMS and controls. Properties of dynamic cerebral autoregulation were inferred from transfer gain, coherence, and phase of the relationship between BP and CBV estimated from filtered data segments (0.02-0.8 Hz). During the 3 min preceding syncope, dynamic cerebral autoregulation of subjects with NMS did not differ from that of controls nor did it change over the course of HUT in patients with NMS or in control subjects. Dynamic cerebral autoregulation was also unaffected by the degree of orthostatic intolerance as inferred from latency to onset of syncope. We conclude that cerebral autoregulation in patients with recurrent syncope does not differ from that of normal control subjects.     

Cerebral blood flow during orthostasis: role of arterial CO2

Reductions in end-tidal Pco(2) (Pet(CO(2))) during upright posture have been suggested to be the result of hyperventilation and the cause of decreases in cerebral blood flow (CBF). The goal of this study was to determine whether decreases in Pet(CO(2)) reflected decreases in arterial Pco(2) (Pa(CO(2))) and their relation to increases in alveolar ventilation (Va) and decreases in CBF. Fifteen healthy subjects (10 women and 5 men) were subjected to a 10-min head-up tilt (HUT) protocol. Pa(CO(2)), Va, and cerebral flow velocity (CFV) in the middle and anterior cerebral arteries were examined. In 12 subjects who completed the protocol, reductions in Pet(CO(2)) and Pa(CO(2)) (-1.7 +/- 0.5 and -1.1 +/- 0.4 mmHg, P < 0.05) during minute 1 of HUT were associated with a significant increase in Va (+0.7 +/- 0.3 l/min, P < 0.05). However, further decreases in Pa(CO(2)) (-0.5 +/- 0.5 mmHg, P < 0.05), from minute 1 to the last minute of HUT, occurred even though Va did not change significantly (-0.2 +/- 0.3 l/min, P = not significant). Similarly, CFV in the middle and anterior cerebral arteries decreased (-7 +/- 2 and -8 +/- 2%, P < 0.05) from minute 1 to the last minute of HUT, despite minimal changes in Pa(CO(2)). These data suggest that decreases in Pet(CO(2)) and Pa(CO(2)) during upright posture are not solely due to increased Va but could be due to ventilation-perfusion mismatch or a redistribution of CO(2) stores. Furthermore, the reduction in Pa(CO(2)) did not fully explain the decrease in CFV throughout HUT. These data suggest that factors in addition to a reduction in Pa(CO(2)) play a role in the CBF response to orthostatic stress.     

Dynamic modulation of cerebrovascular resistance as an index of autoregulation under tilt and controlled PET(CO(2))

Transfer function analysis of the arterial blood pressure (BP)-mean flow velocity (MFV) relationship describes an aspect of cerebrovascular autoregulation. We hypothesized that the transfer function relating BP to cerebrovascular resistance (CVRi) would be sensitive to low-frequency changes in autoregulation induced by head-up tilt (HUT) and altered arterial PCO(2). Nine subjects were studied in supine and HUT positions with end-tidal PCO(2) (PET(CO(2))) kept constant at normal levels: +5 and -5 mmHg. The BP-MFV relationship had low coherence at low frequencies, and there were significant effects of HUT on gain only at high frequencies and of PCO(2) on phase only at low frequencies. BP --> CVRi had coherence >0.5 from very low to low frequencies. There was a significant reduction of gain with increased PCO(2) in the very low and low frequencies and with HUT at the low frequency. Phase was affected by PCO(2) in the very low frequencies. Transfer function analysis of BP --> CVRi provides direct evidence of altered cerebrovascular autoregulation under HUT and higher levels of PCO(2).     

Cerebral circulation during mild +Gz hypergravity by short-arm human centrifuge

We examined changes in cerebral circulation in 15 healthy men during exposure to mild +Gz hypergravity (1.5 Gz, head-to-foot) using a short-arm centrifuge. Continuous arterial pressure waveform (tonometry), cerebral blood flow (CBF) velocity in the middle cerebral artery (transcranial Doppler ultrasonography), and partial pressure of end-tidal carbon dioxide (ETco(2)) were measured in the sitting position (1 Gz) and during 21 min of exposure to mild hypergravity (1.5 Gz). Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis between beat-to-beat mean arterial pressure (MAP) and mean CBF velocity (MCBFV). Steady-state MAP did not change, but MCBFV was significantly reduced with 1.5 Gz (-7%). ETco(2) was also reduced (-12%). Variability of MAP increased significantly with 1.5 Gz in low (53%)- and high-frequency ranges (88%), but variability of MCBFV did not change in these frequency ranges, resulting in significant decreases in transfer function gain between MAP and MCBFV (gain in low-frequency range, -17%; gain in high-frequency range, -13%). In contrast, all of these indexes in the very low-frequency range were unchanged. Transfer from arterial pressure oscillations to CBF fluctuations was thus suppressed in low- and high-frequency ranges. These results suggest that steady-state global CBF was reduced, but dynamic cerebral autoregulation in low- and high-frequency ranges was improved with stabilization of CBF fluctuations despite increases in arterial pressure oscillations during mild +Gz hypergravity. We speculate that this improvement in dynamic cerebral autoregulation within these frequency ranges may have been due to compensatory effects against the reduction in steady-state global CBF.     

Cerebral autoregulation is preserved in postural tachycardia syndrome.

To test whether cerebral autoregulation is impaired in patients with postural tachycardia syndrome (POTS), we evaluated 17 healthy control subjects and 27 patients with POTS. Blood pressure, heart rate, and cerebral blood velocity (transcranial Doppler) were recorded at rest and during 80 degree head-up tilt (HUT). Static cerebral autoregulation, as assessed from the change in cerebrovascular resistance during HUT, was the same in POTS and in controls. The properties of dynamic cerebral autoregulation were inferred from transfer gain, coherence, and phase of the relationship between blood pressure and cerebral blood velocity estimated from filtered data segments (0.02-0.8 Hz). Dynamic cerebral autoregulation of patients with POTS did not differ from that of controls. The patients' dynamic cerebral autoregulation did not change over the course of HUT, despite increased tachycardia suggestive of worsening orthostatic stress. Inflation of military anti-shock trouser pants substantially reduced the tachycardia of patients with POTS without affecting cerebral autoregulation. Symptoms of orthostatic intolerance were reduced in one-half of the patients following military anti-shock trouser pants inflation. We conclude that cerebral perfusion and autoregulation in many patients with POTS do not differ from that of normal control subjects.     

Effect of acute exposure to 3660 m altitude on orthostatic responses and tolerance.

Orthostatic reflexes were examined at 375 m and after 60 min of exposure in a hypobaric chamber at 3660 m using a 20-min 70 degrees head-up tilt (HUT) test. Mean arterial blood pressure, R wave-R wave interval (RRI), and mean cerebral blood flow velocity (MFV) were examined with coarse-graining spectral analysis. Of 14 subjects, 7 at 375 m and 12 at 3660 m were presyncopal. Immediately on arrival to high altitude, breathing frequency and MFV increased, and endtidal PCO2, RRI, RRI complexity, and the parasympathetic nervous system indicator decreased. MFV was similar in HUT at both altitudes. The sympathetic nervous system indicator increased with tilt at 3660 m, whereas parasympathetic nervous system indicator decreased with tilt at both altitudes. Multiple regression analysis of supine variables from either 375 or 3660 m and the time to presyncope at 3660 m indicated that, after 1 h of exposure, increased presyncope at altitude was the result of 1). ineffective peripheral vasoconstriction, despite increased cardiac sympathetic nervous system activity with HUT, and 2). insufficient cerebral perfusion owing to cerebral vasoconstriction as the result of hypoxic hyperventilation-induced hypocapnia.     

Dynamic cerebral autoregulation is preserved during acute head-down tilt.

Complete ganglion blockade alters dynamic cerebral autoregulation, suggesting links between systemic autonomic traffic and regulation of cerebral blood flow velocity. We tested the hypothesis that acute head-down tilt, a physiological maneuver that decreases systemic sympathetic activity, would similarly disrupt normal dynamic cerebral autoregulation. We studied 10 healthy young subjects (5 men and 5 women; age 21 +/- 0.88 yr, height 169 +/- 3.1 cm, and weight 76 +/- 6.1 kg). ECG, beat-by-beat arterial pressure, respiratory rate, end-tidal CO2 concentration, and middle cerebral blood flow velocity were recorded continuously while subjects breathed to a metronome. We recorded data during 5-min periods and averaged responses from three Valsalva maneuvers with subjects in both the supine and -10 degrees head-down tilt positions (randomized). Controlled-breathing data were analyzed in the frequency domain with power spectral analysis. The magnitude of input-output relations were determined with cross-spectral techniques. Head-down tilt significantly reduced Valsalva phase IV systolic pressure overshoot from 36 +/- 4.0 (supine position) to 25 +/- 4.0 mmHg (head down) (P = 0.03). Systolic arterial pressure spectral power at the low frequency decreased from 5.7 +/- 1.6 (supine) to 4.4 +/- 1.6 mmHg2 (head down) (P = 0.02), and mean arterial pressure spectral power at the low frequency decreased from 3.3 +/- 0.79 (supine) to 2.0 +/- 0.38 mmHg2 (head down) (P = 0.05). Head-down tilt did not affect cerebral blood flow velocity or the transfer function magnitude and phase angle between arterial pressure and cerebral blood flow velocity. Our results show that in healthy humans, mild physiological manipulation of autonomic activity with acute head-down tilt has no effect on the ability of the cerebral vasculature to regulate flow velocity.     

Cerebral white matter blood flow is constant during human non-rapid eye movement sleep: a positron emission tomographic study.

This study aimed to identify brain regions with the least decreased cerebral blood flow (CBF) and their relationship to physiological parameters during human non-rapid eye movement (NREM) sleep. Using [(15)O]H(2)O positron emission tomography, CBF was measured for nine normal young adults during nighttime. As NREM sleep progressed, mean arterial blood pressure and whole brain mean CBF decreased significantly; arterial partial pressure of CO(2) and, selectively, relative CBF of the cerebral white matter increased significantly. Absolute CBF remained constant in the cerebral white matter, registering 25.9 +/- 3.8 during wakefulness, 25.8 +/- 3.3 during light NREM sleep, and 26.9 +/- 3.0 (ml.100 g(-1).min(-1)) during deep NREM sleep (P = 0.592), and in the occipital cortex (P = 0.611). The regression slope of the absolute CBF significantly differed with respect to arterial partial pressure of CO(2) between the cerebral white matter (slope 0.054, R = - 0.04) and frontoparietal association cortex (slope - 0.776, R = - 0.31) (P = 0.005) or thalamus (slope - 1.933, R = - 0.47) (P = 0.004) and between the occipital cortex (slope 0.084, R = 0.06) and frontoparietal association cortex (P = 0.021) or thalamus (P < 0.001), and, with respect to mean arterial blood pressure, between the cerebral white matter (slope - 0.067, R = - 0.10) and thalamus (slope 0.637, R = 0.31) (P = 0.044). The cerebral white matter CBF keeps constant during NREM sleep as well as the occipital cortical CBF, and may be specifically regulated by both CO(2) vasoreactivity and pressure autoregulation.     

Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction

Conflicting data exist on the role of nitric oxide (NO) in cerebral blood flow (CBF) autoregulation. Previous studies involving human and animal subjects seem to indicate that NO involvement is limited to the CO(2)-dependent mechanism (chemoregulation) and not to the pressure-dependent autoregulation (mechanoregulation). We tested this hypothesis in patients with impaired endothelial function compared with healthy controls. Blood pressure, heart rate, end-tidal Pco(2), CBF velocities (CBFV), forearm blood flow, and reactive hyperemia were assessed in 16 patients with diabetes mellitus and/or hypertension and compared with 12 age- and sex-matched healthy controls. Pressure-dependent autoregulation was determined by escalating doses of phenylephrine. CO(2) vasoreactivity index was extrapolated from individual slopes of mean CBFV during normocapnia, hyperventilation, and CO(2) inhalation. Measurements were repeated after sodium nitroprusside infusion. Indexes of endothelial function, maximal and area under the curve (AUC) of forearm blood flow (FBF) changes, were significantly impaired in patients (maximal flow: 488 +/- 75 vs. 297 +/- 31%; P = 0.01, AUC DeltaFBF: 173 +/- 17 vs. 127 +/- 11; P = 0.03). Patients and controls showed similar changes in cerebrovascular resistance during blood pressure challenges (identical slopes). CO(2) vasoreactivity was impaired in patients compared with controls: 1.19 +/- 0.1 vs. 1.54 +/- 0.1 cm.s(-1).mmHg(-1); P = 0.04. NO donor (sodium nitroprusside) offsets this disparity. These results suggest that patients with endothelial dysfunction have impaired CO(2) vasoreactivity and preserved pressure-dependent autoregulation. This supports our hypothesis that NO is involved in CO(2)-dependent CBF regulation alone. CBFV chemoregulation could therefore be a surrogate of local cerebral endothelial function.     

Does nitric oxide buffer arterial blood pressure variability in humans?

Animal studies suggest that nitric oxide (NO) plays an important role in buffering short-term arterial pressure variability, but data from humans addressing this hypothesis are scarce. We evaluated the effects of NO synthase (NOS) inhibition on arterial blood pressure (BP) variability in eight healthy subjects in the supine position and during 60 degrees head-up tilt (HUT). Systemic NOS was blocked by intravenous infusion of N(G)-monomethyl-L-arginine (L-NMMA). Electrocardiogram and beat-by-beat BP in the finger (Finapres) were recorded continuously for 6 min, and brachial cuff BP was recorded before and after L-NMMA in each body position. BP and R-R variability and their transfer functions were quantified by power spectral analysis in the low-frequency (LF; 0.05-0.15 Hz) and high-frequency (HF; 0.15-0.35 Hz) ranges. L-NMMA infusion increased supine BP (systolic, 109 +/- 4 vs. 122 +/- 3 mmHg, P = 0.03; diastolic, 68 +/- 2 vs. 78 +/- 3 mmHg, P = 0.002), but it did not affect supine R-R interval or BP variability. Before L-NMMA, HUT decreased HF R-R variability (P = 0.03), decreased transfer function gain (LF, 12 +/- 2 vs. 5 +/- 1 ms/mmHg, P = 0.007; HF, 18 +/- 3 vs. 3 +/- 1 ms/mmHg, P = 0.002), and increased LF BP variability (P < 0.0001). After L-NMMA, HUT resulted in similar changes in BP and R-R variability compared with tilt without L-NMMA. Increased supine BP after L-NMMA with no effect on BP variability during HUT suggests that tonic release of NO is important for systemic vascular tone and thus steady-state arterial pressure, but NO does not buffer dynamic BP oscillations in humans.     

Impaired cerebrovascular autoregulation and reduced CO₂ reactivity after long duration spaceflight

Long duration habitation on the International Space Station (ISS) is associated with chronic elevations in arterial blood pressure in the brain compared with normal upright posture on Earth and elevated inspired CO(2). Although results from short-duration spaceflights suggested possibly improved cerebrovascular autoregulation, animal models provided evidence of structural and functional changes in cerebral vessels that might negatively impact autoregulation with longer periods in microgravity. Seven astronauts (1 woman) spent 147 ± 49 days on ISS. Preflight testing (30-60 days before launch) was compared with postflight testing on landing day (n = 4) or the morning 1 (n = 2) or 2 days (n = 1) after return to Earth. Arterial blood pressure at the level of the middle cerebral artery (BP(MCA)) and expired CO(2) were monitored along with transcranial Doppler ultrasound assessment of middle cerebral artery (MCA) blood flow velocity (CBFV). Cerebrovascular resistance index was calculated as (CVRi = BP(MCA)/CBFV). Cerebrovascular autoregulation and CO(2) reactivity were assessed in a supine position from an autoregressive moving average (ARMA) model of data obtained during a test where two breaths of 10% CO(2) were given four times during a 5-min period. CBFV and Doppler pulsatility index were reduced during -20 mmHg lower body negative pressure, with no differences pre- to postflight. The postflight indicator of dynamic autoregulation from the ARMA model revealed reduced gain for the CVRi response to BP(MCA) (P = 0.017). The postflight responses to CO(2) were reduced for CBFV (P = 0.056) and CVRi (P = 0.047). These results indicate that long duration missions on the ISS impaired dynamic cerebrovascular autoregulation and reduced cerebrovascular CO(2) reactivity.     

External respiration and gas metabolism in orthostatic syncopes

Cardiorespiratory reactions to tilt tests were compared in 80 healthy male subjects with an adequate orthostatic tolerance and in 19 subjects who fainted during tilting. They showed significant differences in the gas exchange, hemodynamics, and external respiration. Variations in the heart rate, pulmonary ventilation and the alveolar CO2 tension were most demonstrative. The findings, particularly the lack of the expected decrease o= oxygen consumption in the presyncopal state contribute to the concepts of the pathogenesis of the orthostatic collapse.     

Cerebral hemodynamics during orthostatic stress assessed by nonlinear modeling.

The effects of orthostatic stress, induced by lower body negative pressure (LBNP), on cerebral hemodynamics were examined in a nonlinear context. Spontaneous fluctuations of beat-to-beat mean arterial blood pressure (MABP) in the finger, mean cerebral blood flow velocity (MCBFV) in the middle cerebral artery, as well as breath-by-breath end-tidal CO2 concentration (P(ET(CO2))) were measured continuously in 10 healthy subjects under resting conditions and during graded LBNP to presyncope. A two-input nonlinear Laguerre-Volterra network model was employed to study the dynamic effects of MABP and P(ET(CO2)) changes, as well as their nonlinear interactions, on MCBFV variations in the very low (VLF; below 0.04 Hz), low (LF; 0.04-0.15 Hz), and high frequency (HF; 0.15-0.30 Hz) ranges. Dynamic cerebral autoregulation was described by the model terms corresponding to MABP, whereas cerebral vasomotor reactivity was described by the model P(ET(CO2)) terms. The nonlinear model terms reduced the output prediction normalized mean square error substantially (by 15-20%) and had a prominent effect in the VLF range, both under resting conditions and during LBNP. Whereas MABP fluctuations dominated in the HF range and played a significant role in the VLF and LF ranges, changes in P(ET(CO2)) accounted for a considerable fraction of the VLF and LF MCBFV variations, especially at high LBNP levels. The magnitude of the linear and nonlinear MABP-MCBFV Volterra kernels increased substantially above -30 mmHg LBNP in the VLF range, implying impaired dynamic autoregulation. In contrast, the magnitude of the P(ET(CO2))-MCBFV kernels reduced during LBNP at all frequencies, suggesting attenuated cerebral vasomotor reactivity under dynamic conditions. We speculate that these changes may reflect a progressively reduced cerebrovascular reserve to compensate for the increasingly unstable systemic circulation during orthostatic stress that could ultimately lead to cerebral hypoperfusion and syncope.     

Dynamic cerebral autoregulation remains stable during physical challenge in healthy persons

The effects of physical activity on cerebral blood flow (CBF) and cerebral autoregulation (CA) have not yet been fully evaluated. There is controversy as to whether increasing heart rate (HR), blood pressure (BP), and sympathetic and metabolic activity with altered levels of CO2 might compromise CBF and CA. To evaluate these effects, we studied middle cerebral artery blood flow velocity (CBFV) and CA in 40 healthy young adults at rest and during increasing levels of physical exercise. We continuously monitored HR, BP, end-expiratory CO2, and CBFV with transcranial Doppler sonography at rest and during stepwise ergometric challenge at 50, 100, and 150 W. The modulation of BP and CBFV in the low-frequency (LF) range (0.04-0.14 Hz) was calculated with an autoregression algorithm. CA was evaluated by calculating the phase shift angle and gain between BP and CBFV oscillations in the LF range. The LF BP-CBFV gain was then normalized by conductance. Cerebrovascular resistance (CVR) was calculated as mean BP adjusted to brain level divided by mean CBFV. HR, BP, CO2, and CBFV increased significantly with exercise. Phase shift angle, absolute and normalized LF BP-CBFV gain, and CVR, however, remained stable. Stable phase shift, LF BP-CBFV gain, and CVR demonstrate that progressive physical exercise does not alter CA despite increasing HR, BP, and CO2. CA seems to compensate for the hemodynamic effects and increasing CO2 levels during exercise.     

Effects of combination alfaxalone and alfadolone, anesthetic derivatives of pregnanedione, on cerebral hemodynamics in cats]

Intravenous injection of CT 1341 (a mixture of alphaxalone and alphadolone dissolved in cremophor el) induced a decrease in cerebral blood flow (CBF) measured by 133Xe clearance in cats with artificial respiration (the mean reduction in CBF was 2 ml/100 g/mn for 1,2 mg/kg or CT 1341. So, CBF was decreased by 22% when CT 1341 (7,2 mg/kg) was intravenously injected, (mean Pa CO2 equals 30 mm Hg). Changes in CBF following CT 1341 intravenous injection seems to be caused by cerebral vascular constriction evidenced by the direct observation of pial vessels. Following intravenous injection of CT 1341 (from 7, 2 mg/kg to 19,2 mg/kg), the cerebrovascular reactivity to hypercapnia or hypocapnia was not affected, but autoregulation of cerebral blood flow was transiently abolished. In animals with free respiration, CBF was increased in relation with the elevation in Pa CO2 caused by the depression of respiration.     

PET(CO(2)) inversely affects MSNA response to orthostatic stress

Arterial hypocapnia has been associated with orthostatic intolerance. Therefore, we tested the hypothesis that hypocapnia may be detrimental to increases in muscle sympathetic nerve activity (MSNA) and total peripheral resistance (TPR) during head-up tilt (HUT). Ventilation was increased approximately 1.5 times above baseline for each of three conditions, whereas end-tidal PCO(2) (PET(CO(2))) was clamped at normocapnic (Normo), hypercapnic (Hyper; +5 mmHg relative to Normo), and hypocapnic (Hypo; -5 mmHg relative to Normo) conditions. MSNA (microneurography), heart rate, blood pressure (BP, Finapres), and cardiac output (Q, Doppler) were measured continuously during supine rest and 45 degrees HUT. The increase in heart rate when changing from supine to HUT (P < 0.001) was not different across PET(CO(2)) conditions. MSNA burst frequency increased similarly with HUT in all conditions (P < 0.05). However, total MSNA and the increase in total amplitude relative to baseline (%DeltaMSNA) increased more when changing to HUT during Hypo compared with Hyper (P < 0.05). Both BP and Q were higher during Hyper than both Normo and Hypo (main effect; P < 0.05). Therefore, the MSNA response to HUT varied inversely with levels of PET(CO(2)). The combined data suggest that augmented cardiac output with hypercapnia sustained blood pressure during HUT leading to a diminished sympathetic response.     

Control of cerebral blood velocity with furosemide-induced hypovolemia and upright tilt

The purpose of this study was to test the hypothesis that exacerbated reductions of cerebral blood velocity (CBV) during upright tilt with dehydration are associated with impaired cerebrovascular control. Nine healthy men were tilted head-up (HUT) to 70° for 10 min on two occasions separated by 7 days under euhydration (EUH) and dehydration (DEH; 40 mg of furosemide and water restriction) conditions. Beat-by-beat arterial pressures and CBV were measured during a 5-min supine baseline and during the first (T1) and last (T2) 5 min of HUT. Cerebral autoregulation and arterial baroreflex sensitivity were assessed in the frequency domain with cross-spectral techniques. DEH reduced plasma volume by 10% (P = 0.008) and supine mean CBV (CBV(mean)) by 11% (P = 0.002). Mean arterial pressure (MAP), stroke volume, and baroreflex sensitivity decreased during HUT (P ≤ 0.002), but absolute reductions were similar between hydration conditions, with the exception of stroke volume, which was lower at T1 during DEH than EUH (P = 0.04). CBV(mean) during DEH was lower (7 cm/s) over the course of the entire 10 min of HUT (P ≤ 0.004) than during EUH. Low-frequency oscillations (0.07-0.2 Hz) of MAP and CBV(mean) and MAP-CBV(mean) coherence were higher during DEH than EUH at T1 (P ≤ 0.02), but not at T2. Our results suggest that increased coherence between arterial pressure and CBV with the combination of DEH and HUT are indicative of altered cerebrovascular control. Increased CBV oscillations with DEH may reflect acute protective mechanisms to ensure adequate cerebral perfusion under conditions of reduced central blood volume.     

Cardiac homeostasis is independent of calf venous compliance in subjects with paraplegia

The purpose of this study was to examine cardiac hemodynamics during acute head-up tilt (HUT) and calf venous function during acute head-down tilt (HDT) in subjects with paraplegia compared with sedentary nondisabled controls. Nineteen paraplegic males (below T6) and nine age-, height-, and weight-matched control subjects participated. Heart rate, stroke volume, and cardiac output were assessed using the noninvasive acetylene uptake method. Venous vascular function of the calf was assessed using venous occlusion plethysmography. After supine measurements were collected, the table was moved to 10 degrees HDT followed by the three levels of HUT (10, 35, and 75 degrees ) in random order. Cardiac hemodynamics were similar between the groups at all positions. Calf circumference was significantly reduced in the paraplegic group compared with the control group (P < 0.001). Venous capacitance and compliance were significantly reduced in the paraplegic compared with control group at supine and HDT. Neither venous capacitance (P = 0.37) nor compliance (P = 0.19) increased from supine with 10 degrees HDT in the paraplegic group. A significant linear relationship was established between supine venous compliance and supine cardiac output in the control group (r = 0.80, P < 0.02) but not in the paraplegic group. The findings of reduced calf circumference and similar venous capacitance at supine rest and 10 degrees HDT in the paraplegic group imply that structural changes may have limited venous dispensability in individuals with chronic paraplegia. Furthermore, the lack of a relationship between supine venous compliance and supine cardiac output suggests that cardiac homeostasis does not rely on venous compliance in subjects with paraplegia.