Microelectrode for measuring local cortical oxygen tension and blood flow in the same microareas of cat cortex

The purpose of this study is to investigate the relationship between changes in cortical Po2 (bPo2) and cortical blood flow when inhalating different oxygen mixtures. Experiments were performed on 31 cats anaesthetized with N2O/O2 plus supplemental drugs for immobilization and analgesia. Cortical Po2 was measured by the polarographic method using 25 microns Pt electrode (coated) and a 250 micron Ag-AgCl2 indifferent electrode, especially designed to rest lightly on the cortex by means of coiled spring support. Using the same electrode but with opposite tip polarization; local cortical blood flow (lCoBF) was measured at the same site by the H2-clearance method. The change of bPo2 in going from FiO2 25% to FiO2 75% was measured at 58 different sites. (Table 2). At 25% FiO2 the mean bPo2 was 24 +/- 16 mm Hg, with a range from 4 to 92 mm Hg. With increased FiO2 to 75% local bPo2 responded quite differently at adjacent sites. At 75% FiO2 the mean bPo2 was 42.7 +/- 32 mm Hg with a range from 10 mm Hg to 198 mm Hg. The bPo2 and lCoBF were both measured at 44 of the 58 different sites. Cortical sites with a resting bPo2 greater than 30 mm Hg at 25% FiO2 had a lCBF = 57 +/- 12 ml/100g m; whereas sites with resting normoxic bPO2 less than 20 mm Hg had a mean ICoBF = 56 +/- 14 ml/100g min.(ABSTRACT TRUNCATED AT 250 WORDS)     

End-tidal carbon dioxide monitoring stabilized hemodynamic changes during ECT

Accumulation of carbon dioxide (CO2) can disturb systemic and cerebral hemodynamics in patients receiving electroconvulsive therapy (ECT). The purpose of this study was to identify the effects of end-tidal CO2 monitoring on hemodynamic changes in patients who received ECT under propofol anesthesia. ECT was prescribed to 40 patients under propofol anesthesia. Ventilation was assisted using a face mask and 100% oxygen, with or without end-tidal CO2 monitoring. Heart rate was significantly increased in patients without end-tidal CO2 monitoring at 1 to 5 minutes after electrical stimulation (p < 0.01). Mean arterial blood pressure and middle cerebral artery blood flow velocity in the group without end-tidal CO2 monitoring were significantly larger than the values in the group with the monitor at 1 to 5 minutes after electrical stimulation. Arterial CO2 tension in the group without end-tidal CO2 monitoring was larger than the value in the group with the monitoring at 1 minute (45+/-5 mm Hg with the monitor and 56+/-8 without the monitor) and 5 minutes (37+/-4 mm Hg with the monitor and 51+/-8 without the monitor) after electrical stimulation (p < 0.01). Application of end-tidal CO2 monitoring is considered beneficial for safe and effective anesthesia management of patients undergoing ECT, especially patients with an intracranial disorder or ischemic heart disease.     

MRI measures of middle cerebral artery diameter in conscious humans during simulated orthostasis

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 approximately 25 mm Hg P(ET)CO(2) (hypocapnia). In the LBNP protocol, subjects experienced 10 minutes each of -20 and -40 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 36+/-3 to 40+/-4 mm Hg, P<0.05) and CFV (from 63+/-4 to 80+/-6 cm/s, P<0.001) but did not change MCA diameters (from 2.9+/-0.3 to 2.8+/-0.3 mm). Hypocapnia produced decreases in both P(ET)CO(2) (24+/-2 mm Hg, P<0.005) and CFV (43+/-7 cm/s, P<0.001) compared with normocapnia, with no change in MCA diameters (from 2.9+/-0.3 to 2.9+/-0.4 mm). During -40 mm Hg LBNP, P(ET)CO(2) was not changed, but CFV (55+/-4 cm/s) was reduced from baseline (58+/-4 cm/s, P<0.05), 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).     

Global cerebral blood flow after CO2 inhalation in normal subjects and patients with panic disorder determined with [15O]water and PET

OBJECTIVE: To determine the effect of CO2 inhalation on global cerebral blood flow (gCBF) and pCO2-adjusted gCBF in normal subjects and panic disorder patients. METHOD: Global cerebral blood flow was determined using quantitative [15O] water imaging in normal subjects (n = 12) and panic disorder patients (n = 14) after inhalations of medical grade air and of 35%/65% CO2/O2 mixture, a known inducer of panic. The gCBF was calculated as an area-weighted mean value. The pCO2 -adjusted gCBF values were calculated based on the formula of Reiman et al. [Am. J. Psychiatr. 143 (1986) 469]. Data were analyzed using repeated-measures ANOVA and regression analyses. RESULTS: The pCO2 values did not differ statistically between normals and panic patients. Panic patients exhibited a decrease in gCBF and stable pCO2-adjusted gCBF values in comparisons of AIR and CO2 inhalations, whereas normals exhibited stable gCBF and increasing pCO2-adjusted gCBF values. CONCLUSIONS: Patients with panic disorder, especially when symptomatic, exhibited an abnormal pattern in gCBF response to provocation.     

Hypercarbia depresses cerebral oxygen consumption during cardiopulmonary bypass

No human studies have systematically examined the relations among PaCO2, cerebral blood flow, and the cerebral metabolic rate for oxygen during hypothermic cardiopulmonary bypass. We varied PaCO2 during hypothermic (26-28 degrees C) cardiopulmonary bypass and estimated the cerebral metabolic rate for oxygen by multiplying cerebral blood flow (measured using xenon-133 clearance) by the cerebral arteriovenous difference in oxygen contents. Patients were randomly assigned to either of two methods of managing PaCO2 (uncorrected for body temperature). In group 1 (PACO2 32-48 mm Hg, n = 13) the mean +/- SD cerebral metabolic rate for oxygen was 0.40 +/- 0.11 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 36 +/- 2.0 mm Hg and 0.40 +/- 0.14 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 45 +/- 2 mm Hg. and 49-72 mm Hg, n = 12) the mean +/- SD cerebral metabolic rate for oxygen was 0.31 +/- 0.09 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 55 +/- 3 mm Hg and 0.21 +/- 0.07 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 68 +/- 2 mm Hg. Group 2 values differed significantly from those in Group 1 (p less than 0.05). In both groups, cerebral blood flow increased as PaCO2 increased. During cardiopulmonary bypass, increasing PaCO2 increases cerebral blood flow and decreases the cerebral metabolic rate for oxygen.     

Hypertension with hemodilution prevents multifocal cerebral hypoperfusion after cardiac arrest in dogs.

BACKGROUND: Improved neurological outcome with postarrest hypertensive hemodilution in an earlier study could be the result of more homogeneous cerebral perfusion and improved O2 delivery. We explored global, regional, and local cerebral blood flow by stable xenon-enhanced computed tomography and global cerebral metabolism in our dog cardiac arrest model. METHODS: Ventricular fibrillation cardiac arrest of 12.5 minutes was reversed by brief cardiopulmonary bypass, followed by life support to 4 hours postarrest. We compared control group I (n = 5; mean arterial blood pressure, 100 mm Hg; hematocrit, greater than or equal to 35%) with immediately postarrest reflow-promoted group II (n = 5; mean arterial blood pressure, 140-110 mm Hg; hypervolemic hemodilution with plasma substitute to hematocrit, 20-25%). RESULTS: After initial hyperemia in both groups, during the "delayed hypoperfusion phase" at 1-4 hours postarrest, global cerebral blood flow was 51-60% of baseline in group I versus 85-100% of baseline in group II (p less than 0.01). Percentages of brain tissue voxels with no flow, trickle flow, or low flow were lower (p less than 0.01) and mean regional cerebral blood flow values were higher in group II (p less than 0.01). Global cerebral oxygen uptake recovered to near baseline values at 3-4 hours postarrest in both groups. Postarrest arterial O2 content, however, in hemodiluted group II was 40-50% of that in group I. Thus, the O2 uptake/delivery ratio was increased (worsened) in both groups at 2-4 hours postarrest. CONCLUSIONS: After prolonged cardiac arrest, immediately induced moderate hypertensive hemodilution to hematocrit 20-25% can normalize cerebral blood flow patterns (improve homogeneity of cerebral perfusion), but does not improve cerebral O2 delivery, since the flow benefit is offset by decreased arterial O2 content. Individualized titration of hematocrit or hemodilution with acellular O2 carrying blood substitute (stroma-free hemoglobin or fluorocarbon solution) would be required to improve O2 uptake/delivery ratio.     

Benefits of the laryngeal mask for airway management during electroconvulsive therapy

Accumulation of carbon dioxide (CO2) can disturb systemic hemodynamics and increase the seizure threshold in patients receiving electroconvulsive therapy (ECT). The purpose of this study was to investigate the effects of the laryngeal mask on blood gas, hemodynamics, and seizure duration during ECT under propofol anesthesia. Ventilation was assisted using either a face mask (n=23) or laryngeal mask (n=23) and 100% oxygen. There was no significant difference in PaO2 between the two groups. PaCO2 was greater in the face mask group than the laryngeal mask group at 3 minutes (54 +/- 11 mm Hg, 41 +/- 8 mm Hg, respectively) and 5 minutes (52 +/- 11 mm Hg, 43 +/- 15 mm Hg, respectively) after electrical stimulation (p<0.01). Mean blood pressure was higher than the corresponding preanesthesia value at 1 to 5 minutes after electrical stimulation in the face mask group and at 1 to 3 minutes after electrical stimulation in the laryngeal mask group. Mean seizure duration in the face mask group was significantly shorter than that in the laryngeal mask group (33 +/- 11 seconds, 42 +/- 10 seconds, respectively p<0.01). The change in PaCO2 was minor in the laryngeal mask group compared with the face mask group and seizure duration was longer in the laryngeal mask group. Laryngeal mask may be suitable for airway management during ECT anesthesia, especially when fitting a face mask is difficult.     

Increases in oxygen consumption without cerebral blood volume change during visual stimulation under hypotension condition.

The magnitude of the blood oxygenation level-dependent (BOLD) signal depends on cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2). Thus, it is difficult to separate CMRO2 changes from CBF and CBV changes. To detect the BOLD signal changes induced only by CMRO2 responses without significant evoked CBF and CBV changes, BOLD and CBV functional magnetic resonance imaging (fMRI) responses to visual stimulation were measured under normal and hypotension conditions in isoflurane-anesthetized cats at 4.7 T. When the mean arterial blood pressure (MABP) decreased from 89+/-10 to 50+/-1 mm Hg (mean+/-standard deviation, n=5) by infusion of vasodilator sodium nitroprusside, baseline CBV in the visual cortex increased by 28.4%+/-8.3%. The neural activity-evoked CBV increase in the visual cortex was 10.8%+/-3.9% at normal MABP, but was negligible at hypotension. Positive BOLD changes of +1.8%+/-0.5% (gradient echo time=25 ms) at normal MABP condition became prolonged negative changes of -1.2%+/-0.3% at hypotension. The negative BOLD response at hypotension starts approximately 1 sec earlier than positive BOLD response, but similar to CBV change at normal MABP condition. Our finding shows that the negative BOLD signals in an absence of CBV changes are indicative of an increase in CMRO2. The vasodilator-induced hypotension model simplifies the physiological source of the BOLD fMRI signals, providing an insight into spatial and temporal CMRO2 changes.     

Cardiovascular and T2–T4 dorsal horn cell responses to gallbladder distention in the cat

Effects of gallbladder distention on blood pressure, heart rate, and T2-T4 dorsal horn cell activity were determined in 18 cats anesthetized with alpha-chloralose. Distention of the gallbladder (10-100 mm Hg) increased blood pressure in 17 of 18 cats, but heart rate was altered in only 2. The gallbladder pressure-blood pressure relation was derived for 11 cats. Pressor responses were greater with greater distending pressures over the gallbladder pressure range of 20-80 mm Hg. The maximum increase in blood pressure was 21 +/- 6 mm Hg at a gallbladder pressure of 80 mm Hg. Effects of gallbladder distention were tested on 64 T2-T4 dorsal horn neurons which met the following criteria: they had a somatic receptive field and were excited or inhibited by electrical stimulation of the left greater splanchnic nerve. In addition, all 64 neurons responded to stimulation of cardiopulmonary sympathetic afferent fibers. Gallbladder distention excited 17 cells and inhibited 9 cells. Responses usually consisted of phasic and tonic components. Significant increases or decreases in cell activity were elicited at a gallbladder pressure of 40 mm Hg. Pressor responses as well as changes in cell activity were abolished or greatly attenuated when both greater splanchnic nerves were sectioned. Vagotomy had no effect. Gallbladder pressure thresholds for a change in blood pressure (27 +/- 3 mm Hg) and cell activity (29 +/- 4 mm Hg) were not significantly different. Cells responding to gallbladder distention were located in laminae IV-VII of the T2-T4 segments. We conclude that gallbladder distention alters cell activity in the upper thoracic spinal cord and increases blood pressure. These findings may explain the phenomenon of chest pain which results from disease of the gallbladder.     

Calcium-dependent and ouabain-resistant oxygen consumption in the rat neurohypophysis

To analyze rapid changes in energy metabolism in the neurohypophysis, pO2 was measured in the tissue in vitro with a miniature O2 electrode (tip diameter less than 100 microns, 90% response time less than 3 s). Electrical stimulation (20 Hz, 5 s) evoked immediate pO2 decreases by 93.4 +/- 10.5 mm Hg (mean +/- S.E.M., n = 12) which lasted for about 1 min and were blocked by tetrodotoxin (1 microM) or sodium cyanide (1 mM). Replacement of Ca2+ in the perifusing medium with Mn2+ reduced the pO2 decreases to 23.1 +/- 4.9% (n = 5) of the value before the replacement. In normal medium, ouabain application (1 mM, 3 min) suppressed the electrically evoked pO2 decreases only slightly to 82.6 +/- 6.5% (n = 5). In the Mn2+ medium, the same ouabain application suppressed the pO2 changes to 28.8 +/- 1.4%. High K+ (70 mM) evoked pO2 decreases by 175.8 +/- 14.9 mm Hg (n = 5) within 1-2 min. These pO2 changes were reduced to 35.6 +/- 3.8% in an Mn2+ medium. Veratridine (100 microM) evoked pO2 decreases by 204.8 +/- 36.3 mm Hg (n = 5). During the pO2 decreases, the effects of electrical or high K+ stimulation on pO2 were blocked. These results indicate that O2 consumption was evoked by electrical stimulation, and probably that high K+ or veratridine application in the neurohypophysis is mainly dependent on extracellular calcium and resistant to ouabain. The relationship between O2 consumption and exocytotic release is discussed.     

Prostanoids determine the range of cerebral blood flow autoregulation of newborn piglets

To assess whether prostanoids have a role in setting the blood pressure limits of cerebral blood flow autoregulation in newborn animals, we measured cerebral blood flow and prostanoid concentrations in blood from the sagittal sinus over a wide range of mean systemic blood pressures (17-117 mm Hg) in eight newborn piglets treated with 30 mg/kg i.v. ibuprofen and in eight vehicle-treated piglets. Blood pressure was adjusted by inflating balloon-tipped catheters placed at the aortic isthmus and root to induce hypertension and hypotension, respectively, 80 minutes apart in each piglet. Cerebral blood flow and concentrations of prostaglandins E and F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 in blood from the sagittal sinus and left subclavian artery were measured 20 minutes before (baseline) and during each blood pressure adjustment. In vehicle-treated piglets, cerebral blood flow was constant at blood pressures between 50 and 90 mm Hg (r = 0.06, p = 0.85). When blood pressure was reduced to less than 50 mm Hg, thromboxane B2 concentration in the sagittal sinus increased by 597 +/- 42% and concentrations of the prostaglandins increased by an average of 308 +/- 45% (p less than 0.05). When blood pressure was raised to greater than 90 mm Hg, concentrations of the prostaglandins increased by an average of 46 +/- 11%, with no change in the concentration of thromboxane B2. Treatment with ibuprofen reduced the baseline concentrations of all prostanoids and prevented their changing during hypotension and hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative measurement of blood flow velocity in feline pial arteries during hemorrhagic hypotension and hypercapnia

Due to methodologic difficulties, few investigations have been made on the blood flow velocity in the cerebral microcirculation. Using a newly developed video camera method, we simultaneously measured the blood flow velocity and diameter of pial arteries during hemorrhagic hypotension, after blood pressure recovery, and during CO2 inhalation in cats. When the mean arterial blood pressure was lowered from 129.7 +/- 6.6 to 71.5 +/- 4.1 mm Hg, the blood flow velocity inevitably decreased from 36.6 +/- 5.3 to 27.0 +/- 3.9 mm/sec (p less than 0.001). The calculated blood flow rate [pi X (diameter/2)2 X flow velocity] was preserved in cases with concomitant vasodilation. Conversely, the blood flow velocity increased from 25.3 +/- 5.1 to 31.0 +/- 5.4 mm/sec (p less than 0.001) after mean arterial blood pressure recovery from 67.1 +/- 3.7 to 129.8 +/- 5.8 mm Hg. The blood flow rate was again preserved in vessels with a vasoconstrictive response. Each pial artery apparently dilated or constricted in proportion to the decrease or increase in flow velocity during blood pressure changes, maintaining a constant cerebral blood flow. This indicated the importance of the pial arteries in the mechanisms of cerebral blood flow autoregulation. During 5% CO2 inhalation, the blood flow velocity increased markedly from 25.4 +/- 4.6 to 37.2 +/- 10.0 mm/sec (p less than 0.05), while the pial artery diameter (85.0 +/- 13.7 microns) increased by 9.6 +/- 1.5% (p less than 0.01). The increased flow velocity might be attributable to preferential dilatation of small arterioles or intraparenchymal vessels during hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)     

呼气末二氧化碳分压水平对慢性阻塞性肺疾病患者中枢驱动和呼吸应答的影响

目的 探讨不同呼气末二氧化碳分压(PETCO2)水平对慢性阻塞性肺疾病(COPD)患者巾枢驱动和呼吸应答的影响.方法 13例稳定期COPD患者和10例健康志愿者常规测定肺通气功能后,采用二氧化碳(CO2)重复呼吸方法 ,增加PETCO2,从45 mm Hg上升至70 mm Hg.连续记录并计算在不同PETCO2水甲时中枢驱动和呼吸应答的各项生理参数.结果 PETCO2达到70mm Hg的实验时间在COPD组为(8.5±1.6)min,正常组为(16.3±3.2)min,差异有统计学意义(P＜0.05).两组的呼吸频牢(RR)均呈线性增加,正常组稍高于COPD组.COPD组潮气量(VT和分钟通气量(VE)在PETCO2=45～55 mm Hg时,呈显著的线性增加,VT山(0.68±0.25)L 上升到(1.04±0.44)L,VE由(10.59±3.36)L/min上升到(20.13±4.52)L/min.在PETCO2=55～70 mm Hg时VT和VE出现平台.正常组VT和VE呈线性增加,高于COPD组.正常组的吸气时间占呼吸周期比值(T1/Ttot)高于COPD组,差异有统计学意义(P＜0.05).COPD组的呼吸困难评分高于正常组,差异有统计学意义(P＜0.05).两组的平均吸气流量(VT/Ti)和膈肌电电压的均方根(RMS)均呈线性增加,COPD组VT/T1在PETCO2=65～70mm Hg时低于正常组,差异有统计学意义(P＜0.05),而不同PETCO2水平时RMS高于正常组,差异有统计学意义(P＜0.05).COPD组VE/RMS呈抛物线样变化,明显低于正常组,差异有统计学意义(P＜0.05).结论在CO2重复呼吸过程中,COPD患者的呼吸应答和中枢驱动在早期表现为线性递增,后期通气量出现平台,通气-中枢耦联显著异常.正常组的呼吸应答和中枢驱动均表现为线性递增,呼吸应答高于COPD组,而中枢驱动低于COPD组.     

Bell-shaped relationship between central blood volume and spontaneous baroreflex function

Spontaneous baroreflex function can be altered by acute changes in central blood volume. Both a reduction in spontaneous baroreflex function at central hypovolemia and augmentation at hypervolemia suggest a dose-effect relationship between central blood volume and spontaneous baroreflex function. However, this relationship has not been quantified over stepwise widespread changes in central blood volume. Twelve individuals underwent central hypovolemia at two levels of lower body negative pressure (LBNP) (-15 mm Hg, LBNP15; -30 mm Hg, LBNP30) and hypervolemia with two discrete infusions of normal saline (NS) (15 ml kg(-1), NS15; total 30 ml kg(-1), NS30). Spontaneous baroreflex function was assessed using transfer function analysis and the sequence method between blood pressure and R-R interval. Both central venous pressure (-0.6-7.9 mm Hg) and left ventricular end-diastolic volume (72.4-133.1 ml) decreased during LBNP and increased after saline infusion. Both spontaneous baroreflex indices of high-frequency transfer function gain (LBNP30, 17.4+/-3.2; LBNP15, 22.3+/-3.8; baseline, 25.6+/-4.1; NS15, 28.5+/-4.2 ms mm Hg(-1), ANOVA P=0.001) and of the sequence slope (LBNP30, 14.4+/-2.2; LBNP15, 17.2+/-2.5; baseline, 20.5+/-2.8; NS15, 24.5+/-3.1 ms mm Hg(-1), ANOVA P=0.001) increased stepwise from hypovolemia of LBNP30 to hypervolemia of NS15. However, these indices were lower at NS30 (high-frequency transfer function gain, 22.0+/-2.2 ms mm Hg(-1), post-hoc P=0.071; sequence slope, 17.7+/-1.7 ms mm Hg(-1), post-hoc P<0.05) than NS15 during hypervolemia. These results indicated that the relationship between central blood volume and spontaneous baroreflex function is apparently bell-shaped, with maximal augmentation at moderate hypervolemia.     

Acute exposure to normobaric mild hypoxia alters dynamic relationships between blood pressure and cerebral blood flow at very low frequency.

Acute hypoxia directly causes cerebral arteriole vasodilation and also stimulates peripheral chemoreceptors to change autonomic neural activity. These changes may alter cerebral vascular modulation. We therefore hypothesized that dynamic cerebral autoregulation would be altered during acute exposure to hypoxia. Fifteen healthy men were examined under normoxic (21%) and hypoxic conditions. Oxygen concentrations were decreased in stepwise fashion to 19%, 17%, and 15%, for 10 mins at each level. Mean blood pressure (MBP) in the radial artery was measured via tonometry, and cerebral blood flow velocity (CBFV) in the middle cerebral artery was measured by transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral and transfer function analysis of beat-by-beat changes in MBP and CBFV. Arterial oxygen saturation decreased significantly during hypoxia, while end-tidal CO2 and respiratory rate were unchanged, as was steady-state CBFV. With 15% O2, very-low-frequency power of MBP and CBFV variability increased significantly by 185% and 282%, respectively. Moreover, transfer function coherence (21% O2, 0.46+/-0.04; 15% O2, 0.64+/-0.04; P=0.028) and gain (21% O2, 0.61+/-0.05 cm/secs/mm Hg; 15% O2, 0.86+/-0.08 cm/secs/mm Hg; P=0.035) in the very-low-frequency range increased significantly by 53% and 48% with 15% O2, respectively. However, these indices were unchanged in low- and high-frequency ranges. Acute hypoxia thus increases arterial pressure oscillations and dependence of cerebral blood flow (CBF) fluctuations on blood pressure oscillations, resulting in apparent increases in CBF fluctuations in the very-low-frequency range. Hypoxia may thus impair dynamic cerebral autoregulation in this range. However, these changes were significant only with hypoxia at 15% O2, suggesting a possible threshold for such changes.     

Changes in regional cortical tissue oxygen tension and cerebral blood flow during temporary middle cerebral artery occlusion in baboons.

Cortical tissue oxygen measured by a platinum cathode, and cerebral blood flow recorded by a hydrogen clearance technique, were measured in 13 baboons before, during and after temporary occlusion of the middle cerebral artery. Mean control pO2 was 23.8 +/- 14 mm Hg and mean flow 51.3 +/- 12 ml/100g/min. During the occlusion, there was a gradation in pO2 from values in the opercular area of 3.6 +/- 5.9 mm Hg, to values in the high parietal area of 11.9 +/- 11.7, these being statistically different (P less than 0.05) from each other. The corresponding flow values were 5.5 +/- 7.5 (opercular) and 22.3 +/- 21.7 ml/100 g/min parietal (P less than 0.01). Following removal of the MCA clip, between 20% and 30% of the electrodes registered an early hyperoxia and hyperaemia, which lasted up to 5 min. A late and prolonged hyperoxia, with less evidence of hyperaemia, was also noted in about 20%. The mean tissue pO2, however, at 5-min intervals up to 40 min following the removal of the clip only reached 60-80% of control values in the most ischaemic areas. Only the parietal region showed a mean pO2 above control levels. The mean flow data were uniformly reduced in all regions to about 80% of control values. During and after a second occlusion in 6 animals, similar changes were noted but with even fewer instances of hyperoxia. The mean oxygen and flow results were lower than with the first occlusion, but the reduction was not significant. There was no overall effect of hypercapnia on cortical tissue pO2 during the control period, but there was a significant (P less than 0.05) reduction during the same procedure after the period of ischaemia. An increase in pO2 during hypercapnia could be observed if there were arousal responses of blood pressure "spikes".     

Changes in human regional cerebral blood flow and cerebral blood volume during visual stimulation measured by positron emission tomography.

The hemodynamic mechanism of increase in cerebral blood flow (CBF) during neural activation has not been elucidated in humans. In the current study, changes in both regional CBF and cerebral blood volume (CBV) during visual stimulation in humans were investigated. Cerebral blood flow and CBV were measured by positron emission tomography using H(2)(15)O and (11)CO, respectively, at rest and during 2-Hz and 8-Hz photic flicker stimulation in each of 10 subjects. Changes in CBF in the primary visual cortex were 16% +/- 16% and 68% +/- 20% for the visual stimulation of 2 Hz and 8 Hz, respectively. The changes in CBV were 10% +/- 13% and 21% +/- 5% for 2-Hz and 8-Hz stimulation, respectively. Significant differences between changes in CBF and CBV were observed for visual stimulation of 8 Hz. The relation between CBF and CBV values during rest and visual stimulation was CBV = 0.88CBF(0.30). This indicates that when the increase in CBF during neural activation is great, that increase is caused primarily by the increase in vascular blood velocity rather than by the increase in CBV. This observation is consistent with reported findings obtained during hypercapnia.     

Effect of nitric oxide blockade by NG-nitro-L-arginine on cerebral blood flow response to changes in carbon dioxide tension.

The importance of nitric oxide (NO) for CBF variations associated with arterial carbon dioxide changes was investigated in halothane-anesthetized rats by using an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (NOLAG). CBF was measured by intracarotid injection of 133Xe. In normocapnia, intracarotid infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent increase of arterial blood pressure and a decrease of normocapnic CBF from 85 +/- 10 to 78 +/- 6, 64 +/- 5, and 52 +/- 5 ml 100 g-1 min-1, respectively. This effect lasted for at least 2 h. Raising PaCO2 from a control level of 40 to 68 mm Hg increased CBF to 230 +/- 27 ml 100 g-1 min-1, corresponding to a percentage CBF response (CO2 reactivity) of 3.7 +/- 0.6%/mm Hg PaCO2 in saline-treated rats. NOLAG attenuated this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined with angiotensin to raise blood pressure to the same level as the highest dose of NOLAG did not affect the CBF response to hypercapnia. L-Arginine significantly prevented the effect of NOLAG on normocapnic CBF as well as blood pressure and also abolished its inhibitory effect on hypercapnic CBF. D-Arginine had no such effect. Decreasing PaCO2 to 20 mm Hg reduced control CBF to 46 +/- 3 ml 100 g-1 min-1 with no further reduction after NOLAG. Furthermore, NOLAG did not change the percentage CBF response to an extracellular acidosis induced by acetazolamide (50 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Autoregulation of cerebral blood flow in patients with orthostatic hypotension after spinal cord injury

Two groups of patients who developed orthostatic hypotension (OH) after spinal cord injury (SCI) were studied. In the first group all patients (4 females and 6 males) were asymptomatic, whereas in the second group (1 female and 9 males) all had clinical manifestations of hypotension. All but 3 patients were tetraplegic, and these patients were paraplegic above the T6 level. For this study blood pressure (BP), heart rate and cerebral blood flow (CBF) velocity were measured simultaneously on a tilt table at 0, 30, 60, and 80 degrees. Cerebral blood flow in the middle cerebral artery was measured bilaterally utilising the transcranial Doppler technique. In asymptomatic patients the mean baseline (0 degrees) BP (110 +/- 16/70 +/- 77 mm Hg systolic/diastolic) was not significantly different from the BP (106 +/- 16/68 +/- 11 mm Hg) of symptomatic patients. The mean maximal change in BP during tilting in the asymptomatic group (-23 +/- 10/10 +/- 7 mm Hg) was also not significantly different when compared to the symptomatic group (-29 +/- 13/11 +/- 6 mm Hg). CBF in the symptomatic group during the hypotensive reaction at 80 degrees was 32.5 +/- 5 cm/sec, while at the same body position in the asymptomatic group it was 40.9 +/- 8 cm/sec (significant at the p less than 0.02). In addition, CBF decreased in the symptomatic group at 80 degrees to 55.5 +/- 9.6% of baseline, while in the asymptomatic group the fall was 69.3 +/- 7.2% (p less than 0.001). Our data suggest that autoregulation of CBF rather than systemic BP plays a dominant role in the adaptation to OH in patients with SCI.     

Haemodynamic effects of hypothalamic disconnection in anaesthetized rats

The aim of the present study was to analyse the haemodynamic effects induced by the hypothalamic disconnection (HD) caudal or rostral to the paraventricular nucleus of the hypothalamus (PVN). Mean arterial pressure (MAP), hindlimb, renal and mesenteric blood flow and vascular conductance (HVC, RVC and MVC, respectively) were measured in urethane (1.2 g/kg, i.v.) anesthetized rats for 60 min after disconnection. HD caudal to the PVN was performed with a double-edged microknife of bayonet shape (R = 1 mm, H= 2 mm) stereotaxically placed, lowered 2.8 mm caudal to the bregma along the midline. The cut was achieved by rotating the microknife 90 degrees right and 90 degrees left. HD rostral to the PVN was performed with the knife placed 0.8 mm caudal to the bregma. Thirty minutes after the hypothalamic disconnection caudal (HD-C), a decrease in MAP was observed (- 14 +/- 3 mm Hg), reaching a 60-min decrease of 30 +/- 3 mm Hg. Hindlimb conductance increased 10 min after HD (156 +/- 14%) and remained elevated throughout the experimental period. On the contrary, we observed a transitory renal vasoconstriction (82 +/- 9%, < or = 20 min) and a late mesenteric vasodilation, starting at 30 min (108 +/- 4%) and reaching 138 +/- 6% at 60 min. In rats with HD rostral to the PVN, we only observed minor changes in the cardiovascular parameters. In the MAP, there was a slight decrease 60 min after the hypothalamic disconnection rostral (HD-R) (-9 +/- 4 mm Hg). There were no significant changes in HVC. RVC and MVC were increased 60 min after the HD-R (116 +/- 12% and 124 +/- 11%, respectively). These results suggest that vasodilation in the hindlimb and in the mesenteric bed could contribute to the observed decrease in MAP in HD caudal to PVN rats.