Cerebral blood flow response to increases in arterial CO2 tension during alfentanil anesthesia in the rabbit.

The stability of cerebral function and blood flow (CBF), and the CBF response to changes in arterial carbon dioxide tension (CBF reactivity) during alfentanil anesthesia were examined in rabbits. This model was first shown to provide stable anesthesia, cortical function, and CBF for 4 h. CBF increased significantly to 159% [of baseline] in the left hemisphere and to 167% in the right within 5 min of an exposure to 5% CO2 (p = 0.009 on the left and p = 0.003 on the right), but then decreased to 123% on the left and to 137% on the right (not significantly different from baseline, p = 0.11 on the left and p = 0.07 on the right) while PaCO2 was still rising. Steady state reactivity levels (0.8 ml 100 g-1/min-1/mm Hg-1 CO2 on the left and 0.65 ml 100 g-1/min-1/mm Hg-1 CO2 on the right) were consistent with previous work and were reached at 20 min. These results suggest that mechanisms other than perivascular hydrogen ion concentration mediate the CBF response to changes in arterial CO2 tension during alfentanil anesthesia.     

Doppler CO2 test as an indicator of cerebral vasoreactivity and prognosis in severe intracranial hemorrhages.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography is a noninvasive, reproducible technique that allows the assessment of CO2-induced cerebral vasomotor reactivity. We investigated the effect of CO2 changes on cerebral blood flow velocity in patients with severe intracranial hemorrhage and evaluated the relation between CO2 reactivity, intracranial pressure, and outcome. METHODS: Transcranial Doppler parameters, intracranial pressure, arterial blood pressure, and PaCO2 were measured simultaneously in 40 patients. To determine CO2 reactivity, the initial PaCO2 of each patient was lowered by at least 6 mm Hg by controlled hyperventilation. Relative CO2 reactivity was defined as the percent change in mean flow velocity per mm Hg PaCO2 (averaged during 20 heart cycles before and after approximately 15 minutes of increased hyperventilation). RESULTS: A significantly reduced relative CO2 reactivity was observed in the patient group compared with a healthy, age-matched control group. Relative CO2 reactivity was maintained significantly better in patients with moderate intracranial pressure than in patients with markedly increased intracranial pressure. An indirect correlation was found between intracranial pressure and relative CO2 reactivity (r = -0.89; p less than 0.001). Clinical outcome was significantly related to the initial relative CO2 reactivity. Whereas the patients with good recovery had shown a largely preserved reactivity (mean +/- SD, 3.4 +/- 0.7%) that did not differ significantly from the control group, there was a continuous decrease up to the patients who died (0.8 +/- 0.3%). CONCLUSIONS: Transcranial Doppler CO2 testing in patients with severe cerebral disease and elevated intracranial pressure provides useful information regarding hemodynamic state, prognosis, and determination of beneficial effects of specific therapy.     

Local vascular response to change in carbon dioxide tension. Long term observation in the cat's brain by means of the hydrogen clearance technique

Thirty six small hydrogen sensitive electrodes were inserted into the brains of 6 cats to evaluate the local vascular response to change in PaCO2, of cortex, subcortical white matter, and caudate nucleus. Repeated measurements (617) of local cerebral blood flow (ICBF) were performed over a period of 12 weeks. Within a PaCO2 range from 19 to 96 mmHg the local response of CBF was linear in most of the regions measured. The absolute local CO2 reactivity (CO2-R) showed a positive correlation to ICBF at PaCO2 = 40 mmHg (ICBF40) with the regression line: absolute CO2-R = 0.02 ICBF40 + 0.22, r = 0.71 (p less than 0.01). Therefore relative ICBF change was calculated in relation to ICBF40 to make comparisons between the CO2 response of different measuring days and of different regions examined. No significant change in relative CO2-R was observed during the 12 weeks interval. Differences of relative CO2-R between investigated regions were insignificant. The uniformity of relative CO2 response might support the hypothesis of a direct effect of PaCO2 or pH on the vessel wall. For comparison of CBF, the individual determination of CBF40 and relative CO2-R would be necessary.     

Measurement of cerebral blood flow in the rat with intravenous injection of [11C]butanol by external coincidence counting: a repeatable and noninvasive method in the brain

No method has been reported for measuring CBF, repeatedly and noninvasively, in the rat brain. A new method is described, which is noninvasive to the brain, skull, or cervical large vessels. Two pairs of coincidence detectors were positioned, one over the rat brain and the other at the loop of a catheter inserted into the femoral artery. The coincidence head curve and arterial curve were recorded after intravenous injection of 1-[11C]butanol in 15 rats. CBF was calculated by one-compartment curve fitting ( CBFo ) from 1-min data and with the recirculation corrected height/area method from 3-min data ( CBFh X 3 min) and 5-min data ( CBFh X 5 min). CBFo agreed well with CBFh X 5 min, although a slight overestimation was observed in CBFh X 3 min. The normal CBFo in the normocapnic group (n = 6, paCO2 36.7 +/- 2.3 mm Hg) was 1.76 +/- 0.49 ml/g min (mean +/- SD). A good correlation was observed between CBFo (y) and PaCO2 (x), and the regression line was y = 0. 0629x -0.715 (r = 0.88, p less than 0.0001). We concluded that this method gives the stable blood flow values noninvasively and with a minimum loss of blood (less than 0.28 ml per measurement). Applications of this method include activation studies, studies on the effect of drugs and treatments, and water and oxygen extraction fraction studies using different tracers in the same rat.     

Response of the cerebral circulation to profound hypocarbia in neonatal lambs

Hyperventilation to extremely low arterial carbon dioxide tension (PaCO2) has been used in the management of persistent pulmonary hypertension in newborn infants. With progressive hypocarbia, cerebral vasoconstriction occurs, raising the concern that extreme hypocarbia may result in cerebral oxygen deprivation. Therefore, I evaluated regulation of the cerebral circulation during acute hypocarbia in 10 newborn lambs. Whole-brain and regional blood flows measured using radioactive microspheres, arterial and venous (sagittal sinus) blood gases, and oxygen contents were measured in each lamb at four arterial carbon dioxide tensions. Whole-brain oxygen delivery, oxygen consumption, and fractional oxygen extraction were calculated. Finally, arterial and venous lactate concentrations were measured to assess cerebral lactate production. Whole-brain blood flow (CBF) decreased in a nonlinear fashion as PaCO2 ranged from 46 to 12 mm Hg [In(CBF) = 0.025(PaCO2) + 3.38; r = 0.70, p less than 0.001]. Similar responses were demonstrated for all regional blood flows examined. Cerebral fractional oxygen extraction (E) increased in a nonlinear fashion [In(1-E) = 0.023(PaCO2)-1.37; r = 0.80, p less than 0.001], and cerebral metabolic rate for oxygen was unchanged with hypocarbia. Cerebral venous lactate concentration increased significantly (3.49 +/- 0.23 vs. 2.01 +/- 0.22 mM, p less than 0.001) during severe hypocarbia (PaCO2 of less than 22 mm Hg), and the arterial-venous lactate concentration difference became negative. These results demonstrate uniform responses of whole-brain and regional blood flows and stable cerebral oxygen consumption during moderate and severe hypocarbia. Although there is evidence for cerebral lactate production during severe hypocarbia, this is not likely to indicate cerebral hypoxia as oxygen consumption does not change.     

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)     

Haemostatic abnormalities, cardiac involvement and serum tumor necrosis factor levels in X-linked dystrophic patients

Left ventricular thrombosis and systemic emboli have been demonstrated to complicate cardiomyopathy in Duchenne and Becker muscular dystrophy (DMD, BMD). We investigated plasma levels of prothrombin fragment 1+2 (F1+2). thrombin-antithrombin III complex (TAT) and circulating levels of tumor necrosis factor-alpha (TNF-alpha), a procoagulant cytokine that has been shown to be elevated in patients with depressed cardiac function, in 20 patients with DMD and 12 patients with BMD as compared with 30 age-matched control subjects. Significantly elevated levels of F1+2 (DMD: 1.4+/-0.8 nmol/l; BMD: 1.8+/-0.8 nmol/l vs. controls: 0.7+/-0.2 nmol/l, p <0.01 and p <0.001, respectively), TAT complexes (DMD: 4.7+/-2.7 microg/l, BMD: 5+/-2.3 microg/l vs. controls: 1.6+/-0.5 microg/l, p <0.001) and TNF-alpha (54+/-9 vs. 25+/-7 pg/ml, p <0.001) were observed in patients with the dystrophic disease compared to control subjects. A significantly negative correlation was also found between F1+2 and TAT complexes and left ventricular ejection fraction (r = -0.65, p <0.0001; r = -0.80, p < 0.0001, respectively) and a positive correlation between F1+2 and TAT complexes and serum TNF-alpha levels (r = 0.67, p <0.0001; r = 0.70, p <0.0001, respectively). Our results indicate a hypercoagulable state in X-linked dystrophic patients. A possible relationship between haemostatic activation, left ventricular dysfunction and TNF-alpha system upregulation may be suggested.     

Cerebrovascular CO2 reactivity in patients with dementia due to multiple infarction in the territory of the perforating artery]

In order to clarify the pathophysiology of dementia due to multiple infarction in the territory of the perforating artery, the reactivity of cerebral vessels to increased carbon dioxide tension was examined in patients with multiple cerebral infarction with or without dementia. The subjects studied were 11 patients with multi-infarct dementia (MID) (age 57-82 years old, mean +/- S.D. 72 +/- 8) and 16 patients with multiple infarction without dementia (MI) (age 51-81 years old, mean +/- S.D. 69 +/- 9). The diagnosis of cerebral infarction was based on the clinical signs and symptoms and findings of magnetic resonance imaging (MRI). Only patients with cerebral infarction located in the perforator territories were included in this study. Dementia was diagnosed by DSM-IIIR criteria. The extent of periventricular high intensity area (PVH) on the T2-weighted image of MRI was classified into 3 subgroups by the criteria of Gerard et al with some modifications. Cerebral blood flow (CBF) was measured by the 133Xe intravenous injection method using a Cerbrograph (Novo), and gray matter flow (F1) and initial slope index (ISI) were calculated. The cerebrovascular reactivity to CO2 was estimated as the increase in F1 or ISI per unit increase in PaCO2 (delta F1/delta PaCO2 or delta ISI/delta PaCO2, respectively) during inhalation of 5% CO2 and as %increase in F1 or ISI per unit increase in PaCO2 (delta F1%/delta PaCO2 or delta ISI%/delta PaCO2, respectively) during inhalation of 5% CO2. 1. CO2 reactivity in both groups. delta F1/delta PaCO2 in the MI and MID groups were 3.2 +/- 1.4 ml/100 g/min/mmHg and 2.0 +/- 1.4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of cerebral hemodynamics with perfusion CT]

We report on the evaluation of cerebral ischemic lesions with perfusion CT. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) of 52 patients mostly with ischemic cerebrovascular disease were analysed using the box-modulation transfer function method with 30 ml of contrast medium intravenously injected at 5 ml/sec. CBF, CBV and MTT of the middle cerebral artery (MCA) territory were 43.5 +/- 4.6 ml/100 g/min, 1.9 +/- 0.2 ml/100 g and 2.9 +/- 0.6 seconds at the unaffected side, and 37.7 +/- 7.3 ml/100 g/min, 2.1 +/- 0.3 ml/100 g, 3.7 +/- 0.9 seconds at the lesion side with stenosis or occlusion in the main MCA trunks or internal carotid artery, respectively. A statistically significant difference was shown in CBF and MTT values. Furthermore, there was a close correlation in CBF values of MCA territories between Xe-CT and perfusion CT (r = 0.645, n = 76, p < 0.0001). MTT showed a positive correlation with CBV in those subjects when MTT was below 4.1 seconds (r = 0.526, p < 0.0001, n = 83). MTT also showed a negative correlation with CBF in those patients when MTT indicated more than 4.1 seconds (r = 0.818, p < 0.001, n = 21). These results suggest that the progression of cerebral ischemia may be classified in 4 stages using perfusion CT. The stages are as follows: stage 0; normal CBF without prolonged MTT and increased CBV, stage 1; relatively increased CBV, stage 2; significantly prolonged MTT, and stage 3; significantly decreased CBF with prolonged MTT.     

Noninvasive assessment of CO2-induced cerebral vasomotor response in normal individuals and patients with internal carotid artery occlusions

To evaluate the CO2-induced vasomotor reactivity of the cerebral vasculature, relative changes of blood flow velocity within the middle cerebral artery were measured by transcranial Doppler ultrasonography during normocapnia and various degrees of hypercapnia and hypocapnia. We studied 40 normal individuals and 40 patients with unilateral and 15 patients with bilateral internal carotid artery occlusions. When blood flow velocity changes as percent of normocapnic values were plotted against end-tidal CO2 volume percent, a biasymptotic curve (a tangent-hyperbolic function) gave the best fit of the scattergram. The distance between the upper and lower asymptotes was defined as cerebral vasomotor reactivity. In the normal individuals, mean +/- SD vasomotor reactivity was 85.63 +/- 15.96%. In patients with internal carotid artery occlusions, vasomotor reactivity was significantly lower than normal on both the occluded (mean 45.2%, median 50.4%; p less than 0.0001) and the nonoccluded (mean +/- SD 67.7 + 13.3%, p less than 0.01) sides in the unilateral group and on both sides (mean +/- SD 36.6 +/- 15.9% and 44.9 +/- 24.6%, p less than 0.0001) in the bilateral group. The difference between vasomotor reactivity for symptomatic and asymptomatic unilateral occlusions was also highly significant (mean 37.6% and 62.9%, p less than 0.006). Vasomotor reactivity was also significantly lower in patients with low-flow infarctions on computed tomography than in patients with normal scans (mean +/- SD 36.7 +/- 25% and 60.2 +/- 16.9%, p less than 0.008). A striking association of low-flow infarctions, ischemic ophthalmopathy, and hypostatic transient ischemic attacks was found with vasomotor reactivities of less than 34% or even paradoxical reactions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of midazolam on cerebral hemodynamics and cerebral vasomotor responsiveness to carbon dioxide

Although it is known that hypercarbia increases and benzodiazepines decrease cerebral blood flow (CBF), the effects of benzodiazepines on CBF responsiveness to CO2 are not well documented. The influence on CBF and CBF-CO2 sensitivity of placebo or midazolam, which is a new water-soluble benzodiazepine, was measured in eight healthy volunteers using the noninvasive 133Xe inhalation method for CBF determination. Under normocarbia, midazolam decreased CBF from 40.6 +/- 3.2 to 27.0 +/- 5.0 ml 100 g-1 min-1 (means +/- SD). At a later session under hypercarbia, CBF was 58.8 +/- 4.4 ml 100 g-1 min-1 after administration of placebo, and 49.1 +/- 10.2 ml 100 g-1 min-1 after midazolam. The mean of the slopes correlating PaCO2 and CBF was significantly steeper with midazolam (2.5 +/- 1.2 ml 100 g-1 min-1 mm Hg-1) than with placebo (1.5 +/- 0.4 ml 100 g-1 min-1 mm Hg-1). Our results suggest that midazolam may be a safe agent to use in patients with intracranial hypertension, since it decreases CBF and thus cerebral blood volume; however, it should be administered with caution in nonventilated patients with increased intracranial pressure, since its beneficial effects on cerebrovascular tone can be readily counteracted by the increase in arterial CO2 tension induced by this drug.     

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.     

Long-lasting reduction of cortical blood flow of the brain after spreading depression with preserved autoregulation and impaired CO2 response

The purpose of the present study was to examine the cerebral perfusion after spreading depression with special emphasis on its relation to the perfusion changes in migraine. The cerebrovascular reactivity to changes of arterial PCO2 tension in the range of 24-70 mm Hg and to changes of MABP in the range of 55-150 mm Hg was studied in the rat brain after one episode of cortical spreading depression. Regional CBF (rCBF) was measured in the frontal, parietal, and occipital cortex, the basal ganglia, and the cerebellum of both hemispheres after the intravenous bolus injection of [14C]iodoantipyrine. rCBF decreased in the cortical regions to 69-73% of control values for 1 h after spreading depression in every single rat, but remained unchanged in the basal ganglia and cerebellum. CBF changed with alterations of arterial carbon dioxide tension in all brain regions. In control regions, CBF changed by 2.8-3.9% per mm Hg PaCO2 change, whereas in the spreading depression cortex, CBF changed by only 1.3-1.5%. The difference between control and spreading depression cortex was significant at p less than 0.001, indicating a reduced CO2 sensitivity of the cortical regions invaded by spreading depression. rCBF remained unchanged in all brain regions in the MABP range of 80-150 mm Hg, reflecting the intact autoregulatory function of the two sides, and at a MABP of less than 80 mm Hg, rCBF decreased in parallel in symmetrical regions. It is concluded that the hypoperfusion after spreading depression is due to a vasoconstrictor stimulus overriding the vasodilatory effect of acid pH.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of dipyridamole and theophylline on rat pial vessels during hypocarbia

Hypocarbia results in an increase in brain adenosine concentrations, presumably because of brain hypoxia associated with hypocarbic vasoconstriction. It was hypothesized that adenosine limits the degree of hypocarbic vasoconstriction. To test this hypothesis, the effects of dipyridamole and theophylline on CO2 reactivity during hypocarbia were investigated in anesthetized rats. Dipyridamole should reduce the vasoconstriction by potentiating adenosine action, whereas theophylline should increase the vasoconstriction by blocking adenosine receptors. Cortical pial arterioles of mechanically ventilated and anesthetized rats were displayed on a video monitor system through a closed cranial window. Arterial blood pressure and oxygen tension were stable. CO2 reactivity, formulated as 100 X [delta diameter (micron)/resting diameter (micron)]/delta PaCO2 (mmHg), in the hypocarbic phase was calculated before and after topical superfusion of dipyridamole (10(-6) M; n = 7) and theophylline (5 X 10(-5) M; n = 6). CO2 reactivity was significantly decreased after superfusion of dipyridamole (0.57 +/- 0.08; mean +/- SEM) as compared with mock cerebrospinal fluid (CSF) (0.97 +/- 0.17, p less than 0.05, n = 7). On the other hand, CO2 reactivity after superfusion of theophylline was increased (1.63 +/- 0.28) as compared with mock CSF (1.00 +/- 0.20, p less than 0.05, n = 6), indicating that adenosine is involved in hypocarbic vasoconstriction.     

Regional cerebral blood flow in children--normal value and regional distribution of cerebral blood flow in childhood

The changes in CBF and rCBF through the entire age range include the rapid period in childhood was reported. Sixteen children between the ages of 1 and 15 and 14 adults were studied. These 30 subjects were either volunteers of out-patients without CT and EEG abnormalities. rCBF was measured by the 133Xe intravenous injection method using Varmet rCBF analyzer. Ther relationship between age and CBF, the correlation coefficient was calculated based on the regression equations and the regression curve with the highest correlation was chosen. For the analysis of rCBF, he mean rCBF values (ISI) of 3 channels corresponding to the frontal, temporal, parietal and occipital lobes were expressed as a percentage of the hemispheric CBF. The hemispheric blood flow (ISI and CBF gray) of children less than 5 years of age was approximately twice that found in adults. This value decreased rapidly with age and in the 10-15 years the blood flow was approximately 1.3-fold that of adults. Thereafter, there was a slow decrease and a negative correlation with age was found. The decrease showed the correlation on the following equations; y = 146.5 - 58.5 log x. (r = -0.903) for ISI and log y = 2.26 - 0.29 log x. (r = -0.881) for CBF gray, which was statistically significant. In contrast, the CBF white showed a slightly higher value in the 1-2 years old children, but thereafter the CBF did not show a notable decreases with age. Through the entire age range, a best fit for the Fw values was found with : y = 18.3 + 37.5/x. (r = 0.798), which was also statistically significant.     

Increased cerebral blood flow in anemic patients on long-term hemodialytic treatment.

CBF was measured in 15 patients on chronic hemodialytic treatment. CBF was measured with xenon-133 inhalation using single photon emission tomography. In addition, computerized tomography (CT) and a neurological examination were done prior to hemodialysis. Mean CBF was 66.2 +/- 17.3 (SD) ml 100 g-1 min-1, which was significantly higher (t-test, p less than 0.05) than for an age-matched control group (54.7 +/- 10.2 ml 100 g-1 min-1). However, the hematocrit for the patients was considerably lower, 0.30 +/- 0.07, as compared to 0.43 +/- 0.03 in the controls. A significant negative correlation was observed between CBF and the hematocrit (y = -1.79x + 120.7, r = -0.71, p less than 0.01). Calculating CBF from this equation in the dialyzed patients using a hematocrit of 0.43 yielded a mean CBF value of 43.7 ml 100 g-1 min-1, i.e., 20% below the expected. Two patients showed a focal CBF decrease. CT showed central or cortical atrophy in five patients, and two had small hypodense lesions. The neurological examination revealed slight to moderate dementia in seven cases. Although mean CBF was found to be increased by 21% as compared to the control group, an even higher CBF level would have been expected to outweigh the decreased oxygen carrying capacity of the blood. The findings suggest a lowered metabolic demand of the brain tissue, probably due to subtle brain damage.     

Cerebral blood flow and CO2 reactivity in patients with transient ischemic attack]

To elucidate the changes in cerebral blood flow (CBF) and CO2 reactivity in patients with transient ischemic attack (TIA), 10 patients with TIA and 5 healthy adults (controls) underwent two consecutive CBF measurements (i.e. the first measurement during room air inhalation and the second measurement during 5%CO2 inhalation). Hemispheric mean CBF was determined by each CBF measurement using 133Xenon inhalation method. CO2 reactivity was evaluated by analysing delta CBF (= mean CBF during hypercapnea-mean CBF at rest) and delta CBF/delta PaCO2. The resting mean CBF values in the bilateral hemispheres (i.e. both of the affected and unaffected hemispheres) were significantly lower in TIA patients than controls (p less than 0.05). Inhalation of 5%CO2 significantly increased mean CBF in TIA patients bilaterally, however the mean CBF value during hypercapnea was again significantly lower in TIA patients than controls (p less than 0.05). CO2 reactivity in TIA patients was not significantly different from controls (p greater than 0.05). The result demonstrated that TIA patients have a chronic and global cerebral oligemia with normal CO2 reactivity. The chronic and global cerebral oligemia may develop a transient ischemic neurological symptom by being superimposed with local decrease of CBF.     

Ultrasonographic assessment of global cerebral blood volume in healthy adults.

The authors describe a new ultrasonographic method for analysis of global cerebral blood volume (CBV) and its application under controlled hyperventilation. CBV was determined as the product of global cerebral blood flow volume (CBF) and global cerebral circulation time. CBF was measured by duplex sonography and calculated as the sum of flow volumes in both internal carotid arteries and vertebral arteries. Extracranial Doppler assessed cerebral circulation time by determining the time interval of echo-contrast bolus arrival between internal carotid artery and contralateral internal jugular vein. Forty-four healthy volunteers (mean age 45 +/- 19 years, range 20-79 years) were studied. Mean CBV was 77 +/- 13 mL. CBV did not correlate with age, end-tidal carbon dioxide level, heart rate, or blood pressure. Hypocapnia was induced in 10 subjects by controlled hyperventilation. Mean reduction of end-tidal carbon dioxide values by 9 +/- 1 mm Hg led to a significant increase in cerebral circulation time (6.1 +/- 0.9 to 8.4 +/- 1.1 second, P < 0.0001) and a significant CBF decrease (742 +/- 85 to 526 +/- 77 mL/min, P < 0.0001), whereas CBV remained unchanged (75 +/- 6 to 73 +/- 10 mL).     

Regional hemodynamic effects of changes in PaCO2 in the vagotomized, sino-aortic de-afferented rat

Rats were anesthetized with urethane (1.5 g/kg i.p.) paralyzed with gallamine (3 mg/kg, i.v.), artificially ventilated and the vagi, carotid sinus and aortic nerves were cut. PaCO2 levels of 16.4 +/- 0.8, 23.3 +/- 1.6, 32.3 +/- 1.8 and 51.9 +/- 2.2 mm Hg were obtained by hyperventilation in 0%, 3%, 5% and 8% CO2 in O2, respectively. Radioactive microspheres labelled with 57Co or 113Sn were injected into the left ventricle and cardiac output and regional blood flows were determined by the 'arterial reference sample' method. Increasing PaCO2 induced an increase in systemic arterial pressure which was predominantly due to a significant increase in total peripheral resistance, while the increase in cardiac output was much less pronounced and no changes in heart rate were observed. The effect of increasing PaCO2 on regional vascular resistance (VR) was not uniformly distributed. CO2 induced a dilatation in the cerebral, bronchial and hepatic artery vascular beds. Coronary VR was not affected while vasoconstriction was induced by CO2 in the other vascular territories. This vasoconstriction was most significant in skeletal muscle, skin, pancreas, large intestine and kidneys. In most of these territories the vasoconstrictor effect of CO2 was observed at PaCO2 levels above 23.3 mm Hg, while between 16.4 and 23.3 mm Hg there was either no change or a decrease in VR. Propranolol and phentolamine (1 mg/kg and 10 mg/kg, i.v., respectively), which caused a 78% +/- 2% adrenergic blockade, significantly reduced the CO2 pressor and vasoconstrictor effects. Our experiments show that, after peripheral chemoreceptor denervation in the rat: (a) there is a direct relationship between PaCO2 and VR mediated by the sympathetic nervous system over the whole range of PaCO2 values from hypocapnia to hypercapnia, and (b) the various vascular territories contribute to a different extent to the CO2-induced changes in total peripheral resistance.     

Comparison between the photoelectric method and H2 clearance method for measuring cerebrocortical blood flow in cats

The photoelectric method using carbon black as a nondiffusible tracer of blood was compared with the hydrogen clearance (H2) method in nine anesthetized cats. A photoelectric apparatus and H2 electrode were applied to a small region of the cerebral cortex (left ectosylvian gyrus) for simultaneous measurement of the regional CBF. The values of CBF(H2) and CBF(photoelectric) were 50.7 +/- 19.2 and 52.1 +/- 14.5 ml.100 g-1.min-1, respectively. CBF(H2) and CBF(photoelectric) were found to correlate well (r = 0.588, p less than 0.01) when changes in CBF were induced by CO2 inhalation, exsanguination, hyperventilation, and occlusion of the middle cerebral artery. The correlation between CBF(H2) and CBF(photoelectric) was much better in the case of intraindividual comparisons (r = 0.957, p less than 0.01). In addition to its merits in common with the H2 clearance method, such as handiness, low cost, and strict regionality, the photoelectric method displayed the following advantages: time-to-time measurements of CBF (less than 20 s), immediate display of the microcirculatory flow pattern, and simultaneous monitoring of cerebral blood volume. However, measurements from deep structures of the brain are better performed by the H2 method despite the disadvantage of the use of a potentially explosive gas.