Hypnotic manipulation of effort sense during dynamic exercise: cardiovascular responses and brain activation.

The purpose of this investigation was to hypnotically manipulate effort sense during dynamic exercise and determine whether cerebral cortical structures previously implicated in the central modulation of cardiovascular responses were activated. Six healthy volunteers (4 women, 2 men) screened for high hypnotizability were studied on 3 separate days during constant-load exercise under three hypnotic conditions involving cycling on a 1) perceived level grade, 2) perceived downhill grade, and 3) perceived uphill grade. Ratings of perceived exertion (RPE), heart rate (HR), blood pressure (BP), and regional cerebral blood flow (rCBF) distributions for several sites were compared across conditions using an analysis of variance. The suggestion of downhill cycling decreased both the RPE [from 13 +/- 2 to 11 +/- 2 (SD) units; P < 0.05] and rCBF in the left insular cortex and anterior cingulate cortex, but it did not alter exercise HR or BP responses. Perceived uphill cycling elicited significant increases in RPE (from 13 +/- 2 to 14 +/- 1 units), HR (+16 beats/min), mean BP (+7 mmHg), right insular activation (+7.7 +/- 4%), and right thalamus activation (+9.2 +/- 5%). There were no differences in rCBF for leg sensorimotor regions across conditions. These findings show that an increase in effort sense during constant-load exercise can activate both insular and thalamic regions and elevate cardiovascular responses but that decreases in effort sense do not reduce cardiovascular responses below the level required to sustain metabolic needs.     

Patterns of cerebral blood flow reactivity in adenosine stress-test in patients with carotid stenosis evaluated with MRI and emission tomography with 99m Tc-HMPAO

In this study we evaluated the adenosine stress-test combined with 99mTc-HMPAO SPECT as a possible tool for evaluation of brain perfusion reserve in patients with various degrees of cortical neurologic damage due to internal carotid artery stenosis. The investigation comprised 37 patients with atherosclerotic carotid disease, in everybody of whom the stenosis was detected by echo-Doppler study of carotids and later in 28 verified also using invasive intraarterial digital subtractive angiography. In everybody the 99mTc-HMPAO SPECT study was performed twice: at rest and during stress-test with intravenous injection of adenosine with the patient in the supine position. It was gathered three groups of patients with different kinds of cerebral blood flow reactivity in adenosine stress-test. Henceforth, we conclude that, first, the 99mTc-HMPAO SPECT adenosin stress challenge of cerebral blood flow is a reliable functional test for every group of patients with extensive atherosclerosis and can be used for detection of patients with exhausted or decreased cerebral perfusion reserve in whom the risk of future cerebral vascular ischaemic events is elevated.     

Regional cerebral blood flow response during and after acute asphyxia in newborn piglets

The hemodynamic response during and after acute asphyxia was studied in 14 newborn piglets. An apnea-like asphyxial insult was produced in paralyzed mechanically ventilated piglets by discontinuing ventilation until the piglets became bradycardic (heart rate less than 80 beats/min). Seven piglets had organ blood flow measured by microspheres at control, during asphyxia (PO2 = 16 +/- 11 Torr, pH = 7.31 +/- 0.07, PCO2 = 47 +/- 9 Torr), and during recovery from asphyxia. During acute asphyxia, rapid organ blood flow redistribution occurred, producing decreased renal and skeletal muscle blood flow, while coronary blood flow increased. Although total brain blood flow changed little during asphyxia, regional cerebral blood flow (rCBF) analysis revealed significant nonhomogeneous blood flow distribution within the brain during asphyxia, with decreases to the cerebral gray and white matter and the choroid plexus, whereas brain stem structures had increased flow. During recovery with reventilation, total brain blood flow increased 24% above control, with a more uniform distribution and increased flow to all brain regions. The time course of rCBF changes during acute asphyxia was then determined in seven additional piglets with CBF measurements made sequentially at 30-60 s, 60-120 s, and 120-180 s of asphyxia. The vasoconstriction seen in cortical structures, concurrent with the reduction in skeletal and kidney blood flow, known to be sympathetically mediated, suggest a selective reflex effect in this brain region. The more gradual and progressive vasodilation in brain stem regions during asphyxia is consistent with chemical control. These findings demonstrate significant regional heterogeneity in CBF regulation in newborn piglets.     

Brain activation by central command during actual and imagined handgrip under hypnosis.

The purpose was to compare patterns of brain activation during imagined handgrip exercise and identify cerebral cortical structures participating in "central" cardiovascular regulation. Subjects screened for hypnotizability, five with higher (HH) and four with lower hypnotizability (LH) scores, were tested under two conditions involving 3 min of 1) static handgrip exercise (HG) at 30% of maximal voluntary contraction (MVC) and 2) imagined HG (I-HG) at 30% MVC. Force (kg), forearm integrated electromyography, rating of perceived exertion, heart rate (HR), mean blood pressure (MBP), and differences in regional cerebral blood flow distributions were compared using an ANOVA. During HG, both groups showed similar increases in HR (+13 +/- 5 beats/min) and MBP (+17 +/- 3 mmHg) after 3 min. However, during I-HG, only the HH group showed increases in HR (+10 +/- 2 beats/min; P < 0.05) and MBP (+12 +/- 2 mmHg; P < 0.05). There were no significant increases or differences in force or integrated electromyographic activity between groups during I-HG. The rating of perceived exertion was significantly increased for the HH group during I-HG, but not for the LH group. In comparison of regional cerebral blood flow, the LH showed significantly lower activity in the anterior cingulate (-6 +/- 2%) and insular cortexes (-9 +/- 4%) during I-HG. These findings suggest that cardiovascular responses elicited during imagined exercise involve central activation of insular and anterior cingulate cortexes, independent of muscle afferent feedback; these structures appear to have key roles in the central modulation of cardiovascular responses.     

Effect of acetazolamide on cerebral blood flow and capillary patency.

This study investigated the effects 2 h after administration of acetazolamide on cerebral blood flow and the pattern of cerebral capillary perfusion. Arterial blood pressure, heart rate, arterial blood gases, and pH were recorded in two groups of rats along with either regional cerebral blood flow or the percentage of capillary volume per cubic millimeter and number per square millimeter perfused as determined in cortical, thalamic, pontine, and medullary regions of the brain. Blood pressure, heart rate, and arterial PCO2 were not significantly different between the rats receiving acetazolamide (100 mg/kg) and the controls. Arterial blood pH was significantly lower in the acetazolamide rats. Blood flow increased significantly in the cortical (+ 102%), thalamic (+ 89%), and pontine (+ 88%) regions receiving acetazolamide. In control rats, approximately 60% of the capillaries were perfused in all of the examined regions. The percentage of capillaries per square millimeter perfused was significantly greater in the cortical (+ 52%), thalamic (+ 49%), and pontine (+ 47%) regions of acetazolamide rats compared with controls. In the medulla the increases in blood flow and percentage of capillaries perfused were not significant. Thus in the regions that acetazolamide increased cerebral blood flow, it also increased the percentage of capillaries perfused.     

Effects of the calcium antagonist NB-818 on cerebral blood flow

The effects of intravenous injection of NB-818, isopropyl methyl 2-carbamoyloxymethyl-6-methyl-4-(2,3-dichlorophenyl)-1,4-dihydropyridine-3,5- dicarboxylate, on regional cerebral blood flow were studied in rabbits and Rhesus monkeys, using the hydrogen clearance technique. The above effects were compared with those of nicardipine and nimodipine. In rabbits, NB-818 (10 micrograms/kg i.v.) increased both cerebral cortical blood flow (rCBF) and cerebellar cortical blood flow by about 80% of the predrug level with a moderate decrease in mean arterial blood pressure, and no increase in skeletal muscle blood flow. The increase in cerebral blood flow with NB-818 was as great as that with nicardipine or nimodipine. In Rhesus monkeys, NB-818 (10-20 micrograms/kg i.v.) increased rCBF by about 30% of the predrug level, and its effect continued 30-60 min after dosing. The increase in rCBF with NB-818 was greater than that with nicardipine. The results from the present study indicate that NB-818 predominantly increases rCBF with a concomitant moderate hypotension, and its action is greater than that of nicardipine or nimodipine.     

Changes in regional cerebral blood flow distribution during postexercise hypotension in humans.

This investigation compared patterns of regional cerebral blood flow (rCBF) during exercise recovery both with and without postexercise hypotension (PEH). Eight subjects were studied on 3 days with randomly assigned conditions: 1) after 30 min of rest; 2) after 30 min of moderate exercise (M-Ex) at 60-70% heart rate (HR) reserve during PEH; and 3) after 30 min of light exercise (L-Ex) at 20% HR reserve with no PEH. Data were collected for HR, mean blood pressure (MBP), and ratings of perceived exertion and relaxation, and rCBF was assessed by use of single-photon-emission computed tomography. With the use of ANOVA across conditions, there were differences (P < 0.05; mean +/- SD) from rest during exercise recovery from M-Ex (HR = +12 +/- 3 beats/min; MBP = -9 +/- 2 mmHg), but not from L-Ex (HR = +2 +/- 2 beats/min; MBP = -2 +/- 2 mmHg). After M-Ex, there were decreases (P < 0.05) for the anterior cingulate (-6.7 +/- 2%), right and left inferior thalamus (-10 +/- 3%), right inferior insula (-13 +/- 3%), and left inferior anterior insula (-8 +/- 3%), not observed after L-Ex. There were rCBF decreases for leg sensorimotor regions after both M-Ex (-15 +/- 4%) and L-Ex (-12 +/- 3%) and for the left superior anterior insula (-7 +/- 3% and -6 +/- 3%), respectively. Data show that there are rCBF reductions within specific regions of the insular cortex and anterior cingulate cortex coupled with a postexercise hypotensive response after M-Ex. Findings suggest that these cerebral cortical regions, previously implicated in cardiovascular regulation during exercise, may also be involved in PEH.     

Development of an automatic ROI setting program for input function determination in 99mTc-ECD non-invasive cerebral blood flow quantification

Non-invasive quantitative measurements are useful for clinical study as these are simple and pain-free procedures. A new non-invasive semi-automatic quantitative measurement method, the improved brain uptake ratio (IBUR) method using ^99mTc-ECD SPECT, has recently been reported. If an automatic ROI setting algorithm could be developed to determine the input function for the IBUR method, analysis of regional cerebral blood flow (rCBF) can be completed within a few min without recourse to complex techniques, through a fully automatic rCBF analysis program. The purpose of this study was to develop an automatic input function determination program for ^99mTc-ECD non-invasive cerebral blood flow quantification and to confirm the feasibility of use of this program.The images of 15 consecutive patients who underwent both ^99mTc-ECD chest RI angiography and SPECT examinations were used for development of the automatic arterial input function program. The images of 69 consecutive patients were used for validation of the program.The coincidence ratio between the ROI automatic method and the manual setting method was 98%. The mean difference in the ROI location was ±6.4 mm in the X direction and ±8.6 mm in the Y direction. Individual rCBF values obtained using these independent techniques were also reasonably well correlated (r = 0.95). The total time for the IBUR analysis using the automatic method is 2–3 min as compared to 20–30 min for the current analysis method. This technique improves the throughput of nuclear medical examinations.     

Severe hemodilutional anemia increases cerebral tissue injury following acute neurotrauma.

Anemia may worsen neurological outcomes following traumatic brain injury (TBI) by undefined mechanisms. We hypothesized that hemodilutional anemia accentuates hypoxic cerebral injury following TBI. Anesthetized rats underwent unilateral TBI or sham injury (n > or = 7). Target hemoglobin concentrations between 50 and 70 g/l were achieved by exchanging 40-50% of the blood volume (1:1) with pentastarch. The effect of TBI, anemia, and TBI-anemia was assessed by measuring brain tissue oxygen tension (Pbr(O(2))), regional cerebral blood flow (rCBF), jugular venous oxygen saturation (Sjv(O(2))), cerebral contusion area, and nuclear staining for programmed cell death. Baseline postinjury Pbr(O(2)) values in the TBI and TBI-anemia groups (9.3 +/- 1.3 and 11.3 +/- 4.1 Torr, respectively) were lower than the uninjured controls (18.2 +/- 5.2 Torr, P < 0.05 for both). Hemodilution caused a further reduction in Pbr(O(2)) in the TBI-anemia group relative to the TBI group without anemia (7.8 +/- 2.7 vs. 14.8 +/- 3.9 Torr, P < 0.05). The rCBF remained stable after TBI and increased comparably after hemodilution in both anemia and TBI-anemia groups. The Sjv(O(2)) was elevated after TBI (87.4 +/- 8.9%, P < 0.05) and increased further following hemodilution (95.0 +/- 1.6%, P < 0.05). Cerebral contusion area and nuclear counts for programmed cell death were increased following TBI-anemia (4.1 +/- 3.0 mm(2) and 686 +/- 192, respectively) relative to TBI alone (1.3 +/- 0.3 mm(2) and 404 +/- 133, respectively, P < 0.05 for both). Hemodilutional anemia reduced cerebral Pbr(O(2)) and oxygen extraction and increased cell death following TBI. These results support our hypothesis that acute anemia accentuated hypoxic cerebral injury after neurotrauma.     

Tracheal blood flow and luminal clearance of 99mTc-DTPA in sheep.

Tracheal blood flow and 99mTc-labeled diethylenetriamine pentaacetic acid (DTPA) clearance were measured in the sheep trachea in vivo. The tracheal arteries were isolated and perfused. An isolated segment of tracheal lumen was filled with Krebs-Henseleit solution containing 99mTc-DTPA, and radioactivity was measured in blood from a catheterized tracheal vein. Infusions at constant pressure of methacholine (n = 5), albuterol (n = 6), and histamine (n = 5) increased arterial inflow [+250 +/- 73.0, +74.2 +/- 22.9, +68.9 +/- 39.2% (SE), respectively] and venous outflow (+49.5 +/- 13.8, +11.6 +/- 4.5, +6.2 +/- 13.9%) but decreased 99mTc-DTPA output (-36.8 +/- 8.4, -20.4 +/- 6.2, -58.1 +/- 11.7%) and concentration (-53.9 +/- 10.1, -27.3 +/- 7.5, -49.3 +/- 14.4%). Phenylephrine (n = 9) decreased arterial inflow (-49.4 +/- 10.0%) and venous outflow (-4.1 +/- 5.9%) but increased 99mTc-DTPA output (+74.6 +/- 44.2%) and concentration (+94.4 +/- 56.6%). When the tracheal arteries were initially perfused at constant flow and the flow rate was then changed, 50% increases in flow (n = 5) increased perfusion pressure (+35.9 +/- 2.2%) and venous outflow (+10.5 +/- 3.8%) but decreased 99mTc-DTPA output (-24.4 +/- 7.8%) and concentration (-30.4 +/- 8.8%). Decreases in flow of 50% (n = 3) and 100% (n = 10) decreased perfusion pressure (-34.2 +/- 4.2, -80.1 +/- 3.5%, respectively) and venous outflow (-11.0 +/- 4.8, -29.7 +/- 7.2%) but increased 99mTc-DTPA output (+45.9 +/- 27.5, +167.4 +/- 70.4%) and concentration (+64.7 +/- 26.7, +305.7 +/- 110.2%).(ABSTRACT TRUNCATED AT 250 WORDS)     

A clinical,pneumoencephalographic and radioisotopic study of normal-pressure communicating hydrocephalus

Human serum albumin labelled with iodine-133 or technetium-99^m was injected by the lumbar or cisternal route into patients suspected of having communicating hydrocephalus, and scintigrams were performed up to 24 hours after injection.The CSF isotope studies were shown to be a valuable adjunct to clinical examination and pneumoencephalography in the diagnosis of hydrocephalus. This was especially true in suspected cases of “normal”-pressure hydrocephalus where there may be considerable uncertainty as to which patients with normal pressure and enlarged ventricles will benefit from a shunting procedure. The CSF isotope study provides useful information to the clinician in differentiating patients with symptomatic hydrocephalus from the larger group with dementia, cerebral atrophy and hydrocephalus ex vacuo.     

Measurement of the blood flow velocity in the pericallosal artery of children with hydrocephalus by transcranial Doppler ultrasonography--preliminary results

AIM: The goal of this study was to evaluate selected parameters of the Doppler curve of the pericallosal artery at children with hydrocephalus. METHODS: 12 patients with hydrocephalus were divided into two groups. Group 1 comprised children needing cerebrospinal fluid drainage, and group 2 comprised children without any indication for drainage or with an already inserted well-functioning drainage system. Dilatation of the cerebral ventricles was determined by transcranial ultrasonography. Following parameters of a blood flow of the pericallosal branch of the anterior cerebral artery: peak systolic blood flow velocity (PSFV), end-diastolic blood flow velocity (EDFV) and resistive index (RI) were observed by transcranial Doppler ultrasonography. Parameters of The Doppler curve were measured without pressure (baseline parameters) and during compression of the anterior fontanelle (pressure provocation test). RESULTS: Group 1: baseline parameters: PSFV 68.9 +/- 13.52 cm/s, EDFV 18.26 +/- 10.39 cm/s, RI 0.76 +/- 0.12; parameters during pressure provocation test: PSFV 66.92 +/- 19.75 cm/s, EDFV 10.88 +/- 11.18 cm/s, RI 0.86 +/- 0.14. Group 2: baseline parameters: PSFV 59.95 +/- 19.38 cm/s, EDFV 20.65 +/- 8 cm/s, RI 0.65 +/- 0.04; parameters during the pressure provocation test: PSFV 57.14 +/- 18.91 cm/s, EDFV 17.7 +/- 8.3 cm/s, RI 0.68 +/- 0.05. CONCLUSION: The results show increased baseline and postcompressive values of RI of pericallosal artery in infants with hydrocephalus before drainage procedure and normal values of RI at children without the need for cerebrospinal fluid drainage or with a well-functioning drainage system.     

Cerebral and intestinal perfusion and metabolism in normocythemic hyperviscous hypoxic newborn pigs.

We studied the effects of hypoxia on cerebral cortical and intestinal perfusion and metabolism in normocythemic hyperviscous newborn pigs. Seven pigs were made hyperviscous by an injection of cryoprecipitate, increasing viscosity from 5.8 +/- 0.9 to 9.0 +/- 1. 2 (SD) cycles/s. Six normoviscous pigs received 0.9% NaCl. Reducing the inspired O(2) decreased the arterial O(2) content (Ca(O(2))) from 9.5 +/- 1.6 to 3.6 +/- 1.3 ml O(2)/100 ml. Increases in brain and decreases in gastrointestinal blood flow at the lower Ca(O(2)) values were similar between the groups. During hypoxia, blood flow to stomach, distal intestinal mucosa, and large intestines was lower (-50, -23, and -28%, respectively) in the hyperviscous than normoviscous group. At the lower Ca(O(2)) values, cerebral cortical vascular resistance decreased in both groups and intestinal vascular resistance increased (+257%) in the hyperviscous but not in the normoviscous group. During hypoxia, systemic oxygen delivery decreased, extraction increased, and uptake did not change; cerebral cortical O(2) delivery, extraction, and uptake did not change; and intestinal O(2) delivery decreased, extraction increased, and uptake did not change in both groups. Our study demonstrated that 1) during hypoxia, increases in systemic O(2) extraction compensated for decreases in delivery and systemic uptake did not change; vasodilation sustained cerebral cortical O(2) delivery and preserved metabolism; increases in intestinal oxygen extraction offset decreases in delivery and uptake was preserved; and 2) nonpolycythemic hyperviscosity did not have a major influence on cardiovascular or metabolic responses to hypoxia, except for modest effects on intestinal resistance and perfusion to certain gastrointestinal regions. We conclude that, under normocythemic conditions, a moderate increase in viscosity does not have a major impact on hemodynamic or metabolic adjustments to hypoxia in newborn pigs.     

Cerebral regional capillary perfusion and blood flow after carbon monoxide exposure.

Alterations in regional cerebral blood flow (rCBF) and percent perfused capillaries (indicative of functional intercapillary distance) were determined in conscious male Long-Evans rats after reducing their blood O2-carrying capacity by exposing them to 1% CO for 12 min. rCBF was determined by the iodoantipyrine method. rCBF increased from a mean of 106 +/- 8 (SE) ml.min-1.100 g-1 before CO exposure to 173 +/- 14 ml.min-1.100 g-1 after CO exposure. There was a greater flow increase (126%) in the cerebral cortex than in the lower brain stem [pons (45%), medulla (39%)]. Presence of fluorescein isothiocyanate-labeled dextran identified the perfused capillaries before and after CO exposure. The volume fraction (Vv) and number/mm2 (Na) of all capillaries (perfused and nonperfused) in a given area of brain were determined after staining for alkaline phosphatase. The percent Vv and percent Na of perfused capillaries increased uniformly (from approximately 50% to approximately 80%) in all parts of the brain after CO exposure. In the presence of tissue hypoxia with undiminished plasma PO2, the brain vasculature allowed greater flow of blood while the microvasculature adjusted to reduce the diffusion distance for O2.     

Differential control of intrarenal blood flow during reflex increases in sympathetic nerve activity

The role of renal sympathetic nerve activity (RSNA) in the physiological regulation of medullary blood flow (MBF) remains ill defined, yet regulation of MBF may be crucial to long-term arterial pressure regulation. To investigate the effects of reflex increases in RSNA on intrarenal blood flow distribution, we exposed pentobarbital sodium-anesthetized, artificially ventilated rabbits (n = 7) to progressive hypoxia while recording RSNA, cortical blood flow (CBF), and MBF using laser-Doppler flowmetry. Another group of animals with denervated kidneys (n = 6) underwent the same protocol. Progressive hypoxia (from room air to 16, 14, 12, and 10% inspired O(2)) significantly reduced arterial oxygen partial pressure (from 99 +/- 3 to 65 +/- 2, 51 +/- 2, 41 +/- 1, and 39 +/- 2 mmHg, respectively) and significantly increased RSNA (by 8 +/- 3, 44 +/- 25, 62 +/- 21, and 76 +/- 37%, respectively, compared with room air) without affecting mean arterial pressure. There were significant reductions in CBF (by 2 +/- 1, 5 +/- 2, 11 +/- 3, and 14 +/- 2%, respectively) in intact but not denervated rabbits. MBF was unaffected by hypoxia in either group. Thus moderate reflex increases in RSNA cause renal cortical vasoconstriction, but not at vascular sites regulating MBF.     

20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat

This study examined the effects of blocking the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) on the acute fall in cerebral blood flow after subarachnoid hemorrhage (SAH) in the rat. In vehicle-treated rats, regional cerebral blood flow (rCBF) measured with laser-Doppler flowmetry fell by 30% 10 min after the injection of 0.3 ml of arterial blood into the cisterna magna, and it remained at this level for 2 h. Pretreatment with inhibitors of the formation of 20-HETE, 17-octadecynoic acid (17-ODYA; 1.5 nmol intrathecally) and N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine (HET0016; 10 mg/kg iv), reduced the initial fall in rCBF by 40%, and rCBF fully recovered 1 h after induction of SAH. The concentration of 20-HETE in the cerebrospinal fluid rose from 12 +/- 2 to 199 +/- 17 ng/ml after SAH in vehicle-treated rats. 20-HETE levels averaged only 15 +/- 11 and 39 +/- 13 ng/ml in rats pretreated with 17-ODYA or HET0016, respectively. HET0016 selectively inhibited the formation of 20-HETE in rat renal microsomes with an IC(50) of <15 nM and human recombinant CYP4A11, CYP4F2, and CYP4F3 enzymes with an IC(50) of 42, 125, and 100 nM, respectively. These results indicate that 20-HETE contributes to the acute fall in rCBF after SAH in rats.     

Evidence for central command activation of the human insular cortex during exercise.

The purpose of this investigation was to determine whether central command activated regions of the insular cortex, independent of muscle metaboreflex activation and blood pressure elevations. Subjects (n = 8) were studied during 1) rest with cuff occlusion, 2) static handgrip exercise (SHG) sufficient to increase mean blood pressure (MBP) by 15 mmHg, and 3) post-SHG exercise cuff occlusion (PECO) to sustain the 15-mmHg blood pressure increase. Data were collected for heart rate, MBP, ratings of perceived exertion and discomfort, and regional cerebral blood flow (rCBF) by using single-photon-emission computed tomography. When time periods were compared when MBP was matched during SHG and PECO, heart rate (7 +/- 3 beats/min; P < 0.05) and ratings of perceived exertion (15 +/- 2 units; P < 0.05) were higher for SHG. During SHG, there were significant increases in rCBF for hand sensorimotor (9 +/- 3%), right inferior posterior insula (7 +/- 3%), left inferior anterior insula (8 +/- 2%), and anterior cingluate regions (6 +/- 2%), not found during PECO. There was significant activation of the inferior (ventral) thalamus and right inferior anterior insular for both SHG and PECO. Although prior studies have shown that regions of the insular cortex can be activated independent of mechanoreflex input, it was not presently assessed. These findings provide evidence that there are rCBF changes within regions of the insular and anterior cingulate cortexes related to central command per se during handgrip exercise, independent of metaboreflex activation and blood pressure elevation.     

Hyperbaric Oxygen Reduces Cerebral Blood Flow by Inactivating Nitric Oxide

Based on recent evidence that nitric oxide (NO(.)) is involved in hyperoxic vasoconstriction, we tested the hypothesis that decreases in NO(.) availability in brain tissue during hyperbaric oxygen (HBO(2)) exposure contribute to decreases in regional cerebral blood flow (rCBF). rCBF was measured in rats exposed to HBO(2) at 5 atmospheres (ATA) and correlated with interstitial brain levels of NO(.) metabolites (NO(X)) and production of hydroxyl radical ((.)OH). Changes in rCBF were also correlated with the effects of NO(.) synthase inhibitor (l-NAME), NO(.) donor PAPANONOate, and intravascular superoxide dismutase (MnSOD) during HBO(2). After 30 min of O(2) exposure at 5 ATA, rCBF had decreased in the substantia nigra, caudate putamen, hippocampus, and parietal cortex by 23 to 37%. These reductions in rCBF were not augmented by exposure to HBO(2) in animals pre-treated with l-NAME. After 30 min at 5 ATA, brain NO(X) levels had decreased by 31 +/- 9% and correlated with the decrease in rCBF, while estimated (.)OH production increased by 56 +/- 8%. The decrease in rCBF at 5 ATA was completely abolished by MnSOD administration into the circulation before HBO(2) exposure. Doses of NO(.) donor that significantly increased rCBF in animals breathing air had no effect at 5 ATA of HBO(2). These results indicate that decreases in rCBF with HBO(2) are associated with a decrease in effective NO(.) concentration and an increase in ROS production in the brain. The data support the hypothesis that inactivation of NO(.) antagonizes basal relaxation of cerebral vessels during HBO(2) exposure, although an effect of HBO(2) on NO(.) synthesis has not been excluded.     

Impaired cerebral autoregulation in obstructive sleep apnea

Obstructive sleep apnea (OSA) increases the risk of stroke independent of known vascular and metabolic risk factors. Although patients with OSA have higher prevalence of hypertension and evidence of hypercoagulability, the mechanism of this increased risk is unknown. Obstructive apnea events are associated with surges in blood pressure, hypercapnia, and fluctuations in cerebral blood flow. These perturbations can adversely affect the cerebral circulation. We hypothesized that patients with OSA have impaired cerebral autoregulation, which may contribute to the increased risk of cerebral ischemia and stroke. We examined cerebral autoregulation in patients with and without OSA by measuring cerebral artery blood flow velocity (CBFV) by using transcranial Doppler ultrasound and arterial blood pressure using finger pulse photoplethysmography during orthostatic hypotension and recovery as well as during 5% CO(2) inhalation. Cerebral vascular conductance and reactivity were determined. Forty-eight subjects, 26 controls (age 41.0+/-2.3 yr) and 22 OSA (age 46.8+/-2.3 yr) free of cerebrovascular and active coronary artery disease participated in this study. OSA patients had a mean apnea-hypopnea index of 78.4+/-7.1 vs. 1.8+/-0.3 events/h in controls. The oxygen saturation during sleep was significantly lower in the OSA group (78+/-2%) vs. 91+/-1% in controls. The dynamic vascular analysis showed mean CBFV was significantly lower in OSA patients compared with controls (48+/-3 vs. 55+/-2 cm/s; P <0.05, respectively). The OSA group had a lower rate of recovery of cerebrovascular conductance for a given drop in blood pressure compared with controls (0.06+/-0.02 vs. 0.20+/-0.06 cm.s(-2).mmHg(-1); P <0.05). There was no difference in cerebrovascular vasodilatation in response to CO(2). The findings showed that patients with OSA have decreased CBFV at baseline and delayed cerebrovascular compensatory response to changes in blood pressure but not to CO(2). These perturbations may increase the risk of cerebral ischemia during obstructive apnea.     

Differing effects of vasopressin on regional cerebral blood flow of dogs following intracisternal vs. intra-arterial administration

We investigated the differential effect of the intracisternal and intraarterial administration of vasopressin on the regional cerebral blood flow (rCBF) in the parietal cortex of dogs. Regional CBF, velocity and blood volume were assayed by laser flowmetry. The intracisternal injection of 1 nmol vasopressin significantly increased the rCBF and velocity, without affecting blood volume. However, the intravertebral arterial injection of 1 nmol vasopressin significantly decreased the rCBF and velocity. This discrepancy can be explained by a difference in the affected vasculature; large blood vessels in the subarachnoid space vs. whole cerebral vascular system. The intracisternal and intraarterial injection of the nitric oxide inhibitor N^G-monomethyl-L-arginine reduced the rCBF from the base line, and significantly suppressed the rCBF elevation induced by vasopressin. The effect of vasopressin may be considered as the summation of the increased flow from the dilated large vessels via the release of nitric oxide from the endothelium, and of the decreased flow from the contracted small vessels.