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)     

Comparison between pial and intraparenchymal vascular responses to sympathetic stimulation under hypercapnic conditions. With special reference to the mechanism for escape phenomenon

We have shown that secondary vasodilation ('escape' phenomenon) during sympathetic nerve stimulation occurs in the intraparenchymal vessels but not remarkable in the pial vessels. To test a possible role of CO2 accumulation in the brain tissue in this phenomenon, the responses of pial and intraparenchymal vessels to sympathetic nerve stimulation were investigated during hypercapnia in 9 cats by using a video camera photoelectric system. The ipsilateral superior cervical ganglion was electrically stimulated for 5 min during hypercapnia (PaCO2 = 50 +/- 2 mm Hg). The intraparenchymal vessels as well as pial vessels remained constricted throughout the stimulation. Secondary dilation of the intraparenchymal vessels as seen at the later stage of sympathetic stimulation during normocapnia was not observed under the hypercapnic conditions. We assume that the arterial CO2 tension was so high that the constriction of inflow vessels could not result in accumulation of CO2 in the brain parenchyma. The accumulation of chemical metabolites as represented by CO2 is therefore considered to be the most probable mechanism underlying the escape phenomenon of the intraparenchymal vessels.     

Local cerebral blood flow response to locally infused 2-chloroadenosine during hypotension in piglets

Brain interstitial adenosine increases during hypotension in piglets. If adenosine is to participate in the regulation of neonatal cerebral blood flow (CBF) during hypotension, it must retain its vasodilatory action under that condition. To examine this issue, we studied the effects of locally infused 2-chloroadenosine (2-CADO), a stable adenosine analog, on local CBF in the piglet frontal cortex during normotension and graded hemorrhagic hypotension. We used the modified brain microdialysis/hydrogen clearance technique to simultaneously infuse 2-CADO into the frontal cortex and measure local CBF from the same area. When 2-CADO from 10(-8) M to 10(-3) M was infused under control conditions (n = 7), CBF increased 61% at 10(-5) M, 167% at 10(-4) M, and 210% at 10(-3) M. In hypotension experiments, local infusion of 10(-5) M 2-CADO (n = 8) caused significant increases in CBF (P less than 0.05) under control conditions (MABP = 65 mmHg) and at hypotensive blood pressures of 55 mmHg and 44 mmHg, respectively. At a blood pressure of 33 mmHg, however, infusion of the analog failed to increase CBF. Local infusion of 10(-3) M 2-CADO also produced a similar change in CBF during graded hypotension. These results indicate that 2-CADO dilates intracerebral vessels during normotension, and mild and moderate hypotension, and support the hypothesis that endogenous adenosine mediates autoregulatory adjustments of CBF during hypotension in newborn piglets.     

Causes of excessive daytime sleepiness in hypercapnic and normocapnic obstructive sleep apnea patients

Daytime sleepiness assessed using the Epworth sleepiness scale (ESS) and polysomnography results were compared in 43 patients with obstructive sleep apnea (OSA) with concomitant chronic hypercapnia (PaCO2 53 +/- 6 mmHg), and in 58 patients with the OSA syndrome accompanied by normocapnia (PaCO2 < or = 45 mmHg, mean 39 +/- 3 mmHg). The OSA patients with hypercapnia were more sleepy than those with normocapnia (ESS 18 +/- 7 vs 15 +/- 7, p < 0.05), but apnea index values were similar in both groups (54 +/- 20 and 49 +/- 17). The following parameters of electrophysiological sleep structure were obtained in the hypercapnic OSA patients: sleep stage 1: 66 +/- 28%, stage 2: 28 +/- 27%, stage 3 + 4: 1 +/- 1%, REM sleep 5 + 6% of the total sleep time, while in the OSA patients with normocapnia: stage 1: 39 +/- 19%, stage 2: 28 +/- 27%, stage 3 + 4: 2 +/- 2%, and REM sleep 6 +/- 7% of the total sleep time. Stage 1 NREM sleep was found to be longer, and stage 2 NREM--shorter in hypercapnic than in normocapnic OSA patients (p < 0.01). CONCLUSION: Increased daytime sleepiness in both groups patients with the OSA syndrome is due to sleep fragmentation as well as to deficiency of deep and paradoxical sleep (almost absent deep sleep and extremely shortened REM sleep). Hypercapnic OSA patients' more marked sleepiness may result from a more pronounced disturbance of their sleep macrostructure, with a considerable predomination of stage I NREM sleep.     

Multimodality monitoring during passive tilt and Valsalva maneuver under hypercapnia.

In occlusive cerebrovascular disease cerebral blood flow (CBF) autoregulation can be impaired and constant CBF during fluctuations in blood pressure (BP) cannot be guaranteed. Therefore, an assessment of cerebral autoregulation should consider not only responsiveness to CO2 or Diamox. Passive tilting (PT) and Valsalva maneuver (VM) are established tests for cardiovascular autoregulatory function by provoking BP changes. To develop a comprehensive test for vasomotor reactivity with a potential increase of sensitivity and specificity, the authors combined these maneuvers. Blood pressure, corrected to represent arterial pressure at the level of the circle of Willis, middle cerebral artery Doppler frequencies (DF), heart rate (HR) and endtidal partial pressure of CO2 (PtCO2) were measured continuously and noninvasively in 81 healthy subjects (19-74 years). Passive tilt and Valsalva maneuver were performed under normocapnia (mean, 39 + 4 mmHg CO2) and under hypercapnia (mean, 51 + 5 mm Hg CO2). Resting BP, HR, and DF increased significantly under hypercapnia. Under normocapnia and hypercapnia, PT induced only minor, nonsignificant changes in mean BP at the level of the circle of Willis compared to baseline (normocapnia: + 2 + 15 mm Hg; hypercapnia: -3 +/- 13 mm Hg). This corresponded with a nonsignificant decrease of the mean of DF (normocapnia: -4 +/- 11%; hypercapnia -6 +/- 12%). Orthostasis reduced pulsatility of BP by a predominantly diastolic increase of BP without significant changes in pulsatility of DF. Valsalva maneuver, with its characteristic rapid changes of BP due to elevated intrathoracic pressure, showed no significant BP differences in changes to baseline between normocapnic and hypercapnic conditions. Under both conditions the decrease in BP in phase II was accompanied by significantly increased pulsatility index ratio (PIDF/PIBP). Valsalva maneuver and PT as established tests in autonomic control of circulation provoked not only changes in time-mean of BP but also in pulsatility of BP. The significant increase in pulsatility ratio and decrease of the DF/BP ratio during normocapnia and hypercapnia indicated preserved CBF autoregulation within a wide range of CO2 partial pressures. Hypercapnia did not significantly influence the autoregulatory indices during VM and PT. Physiologically submaximally dilated cerebral arterioles can guarantee unchanged dynamics of cerebral autoregulation. Combined BP and MCA-DF assessment under hypercapnia enables investigating the effect of rapid changes of blood pressure on CO2-induced predilated cerebral arterioles. Assuming no interference of hypercapnia-induced vasodilation, VM, with its rapid, distinct changes in BP, seems especially to be adequate provocation for CBF autoregulation. This combined vasomotor reactivity might provide a more sensitive diagnostic tool to detect impaired cerebral autoregulation very early.     

Cerebral vasoconstriction in response to hypocapnia is maintained after ischemia/reperfusion injury in newborn pigs.

BACKGROUND AND PURPOSE: Hypocapnic cerebral vasoconstriction is used therapeutically to reduce elevated intracranial pressure caused by cerebral edema. Because cerebral ischemia/reperfusion injury causes a selective loss of prostanoid-dependent responses, including vasodilation to hypercapnia, we designed these experiments to examine the effect of ischemia/reperfusion on hypocapnic cerebral vasoconstriction. METHODS: Microvascular responses were studied in 10 newborn pigs (closed cranial window) in response to hyperventilation-induced hypocapnia (PaCO2, 22 +/- 2 mm Hg) both before and 45 minutes after 20 minutes of global cerebral ischemia. Responses to hypercapnia (PaCO2, 63 +/- 3 mm Hg), topical isoproterenol (10(-7) M), and norepinephrine (10(-4) M) were also studied before and after ischemia in the same animals for comparison. RESULTS: Before ischemia/reperfusion, pial arterioles vasoconstricted to hypocapnia (-17 +/- 2%) and norepinephrine (-35 +/- 4%) and vasodilated to CO2 (37 +/- 7%) and isoproterenol (25 +/- 2%). After ischemia/reperfusion, the constriction of pial arterioles to hypocapnia (-19 +/- 2%) was similar to that before ischemia. This is in contrast to the loss of dilation to hypercapnia. Dilation to isoproterenol and constriction to norepinephrine were not affected by ischemia. CONCLUSIONS: Hypocapnic cerebral vasoconstriction is maintained after ischemia/reperfusion. Since prostanoid-dependent responses, such as hypercapnic dilation, are lost following cerebral ischemia, these data suggest that hypocapnic constriction is not dependent on an intact prostanoid system and that cerebral vascular responses to CO2 involve multiple mechanisms, depending on whether CO2 is increasing or decreasing from baseline.     

Abnormal cerebrovascular response to altered PaCO2 in baboons with obstructive jaundice.

The cerebrovascular response to hypercapnia and hyperventilation was studied in normal and jaundiced baboons by the intracarotid 133Xe injection technique. The baboons with bile duct ligation were found to have decreased CBF at all levels of PaCO2. This difference between normal and jaundiced baboons was 13% at normocapnia rising to 33% with hypercapnia and 37% with hypocapnia. The CBF values all were increased toward normal by use of an alpha-adrenoreceptor blockade (phentolamine). It is suggested that the obstructive jaundice potentiated an inherent vasoconstrictor alpha-adrenergic mechanism to oppose the effects of CO2. Also, alteration of the PaCO2 may have produced its effects on the cerebral vessels by altering this adrenergic mechanism.     

Selective attenuation by perivascular blood of prostanoid-dependent cerebrovascular dilation in piglets

Cerebral hemorrhagic insults are common in neonates. However, the consequences of intracranial blood on cerebral hemodynamics are poorly understood. We examined the effects of perivascular blood on cerebrovascular dilator responses in 29 piglets. Fresh, autologous blood (n = 15) or cerebrospinal fluid (n = 14) was placed under the dura mater over the parietal cortex, and the piglets were allowed to recover from anesthesia. One to four days later, a closed cranial window was placed over the parietal cortex and pial arteriolar responses to arterial hypercapnia (PaCO2 greater than 55 mm Hg), hemorrhagic hypotension (mean arterial blood pressure less than 35 mm Hg), or topical application of 10(-6) and 10(-4) M isoproterenol were determined. Pial arterioles in the cerebrospinal fluid group dilated 27 +/- 4% (mean +/- SEM) (n = 11) in response to hypercapnia, 26 +/- 5% (n = 9) in response to hypotension, and 26 +/- 3% in response to 10(-6) M and 40 +/- 4% in response to 10(-4) M isoproterenol (n = 11). In the group in which blood was placed on the parietal cortex, pial arterioles did not dilate significantly in response to hypercapnia (8 +/- 3%, n = 11) or hypotension (2 +/- 5%, n = 13) but dilated normally in response to isoproterenol (25 +/- 5% in response to 10(-6) M and 36 +/- 7% in response to 10(-4) M, n = 13). We conclude that prolonged contact of pial arterioles with extravascular blood selectively attenuates cerebrovascular dilation in piglets.     

Responses of cerebral arteries to the changes in cerebral perfusion pressure

The responsiveness of cerebral pial arteries and arterioles to changes in systemic arterial blood pressure (SAP) was investigated. Using 9 cats anesthetized with chloralose and urethane, direct, simultaneous measurements of pial arterial pressure (PAP) and cerebral blood flow (CBF) were made during changes in SAP. SAP was varied between 25 and 140 mmHg by the hemorrhage and blood infusion methods. After a partial craniotomy. PAP was measured with a micropipette connected to a servo-controlled micropressure recording system. Punctured pial arteries were grouped into three types according to their diameters, 1A (291 +/- 33 microns), 2A (16 +/- 26 microns), and 3A (70 +/- 10 microns). CBF on the exposed cortex was measured with hydrogen clearance method. The PAPs measured were a linear function of SAP; PAP (1A) = 0.73/SAP-6.6 (r = 0.96), PAP (2A) = 0.62 X SAP-6.6 (r = 0.90), PAP (3A) = 0.61 X SAP-6.4 (r = 0.93). The result indicates that PAPs are entirely dependent on SAP and that SAP induced changes in PAPs are less in the smaller pial arteries. Regional CBF remained constant (55 +/- 4 ml/100 g/min) between 60 and 140 mmHg of SAP. A significant decrease in CBF was observed below 60 mmHg of SAP. Cerebrovascular resistances were calculated segmentally using the following formulas; large vessel resistances (LVR) = (SAP-PAP(1A]/CBF, middle vessel resistance = (PAP (1A)-PAP (3A]/CBF, and small vessel resistance = PAP (3A)/CBF. The changes in LVR, MVR, and SVR were almost identical between 70 and 140 mmHg of SAP. Below 70 mmHg of SAP, SVR showed the greatest decrease in resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intravenous dipyridamole on cerebral blood flow in humans. A PET study.

BACKGROUND AND PURPOSE: Dipyridamole increases the concentration of circulating adenosine, which is a potent vasodilator, by inhibition of uptake of adenosine into the erythrocytes, and hence produces coronary vasodilation. However, the effects of dipyridamole on cerebral circulation is not pronounced. This study investigates the effects of intravenous dipyridamole on cerebral blood flow (CBF) in humans with use of positron emission tomography (PET). METHODS: In each of 13 healthy subjects, CBF was measured using (15)O-labeled water and PET at rest and during hypercapnia, hypocapnia, and dipyridamole stress; corresponding CBF values were then compared. RESULTS: CBF values during dipyridamole stress were significantly lower than those measured at rest. The dipyridamole stress PaCO(2) was also significantly lower than the resting PaCO(2). The change in CBF during dipyridamole stress relative to PaCO(2) closely followed the relationship between CBF and PaCO(2) during hypocapnia. CONCLUSIONS: These results indicate that the observed decrease in CBF during dipyridamole stress was caused by a decrease in PaCO(2) rather than by any direct action of dipyridamole on CBF. The decrease in PaCO(2) during dipyridamole stress was most likely due to hyperventilation, which was a side effect of adenosine. These results support the hypothesis that circulating adenosine is largely prevented from binding to adenosine receptors of cerebral vessels by the blood-brain barrier.     

The effects of graded hypercapnia on the activation flow coupling response due to forepaw stimulation in alpha-chloralose anesthetized rats

Activation flow coupling (AFC), changes in cerebral blood flow (CBF) due to changes in neural activity with functional stimulation, provides the physiological basis of many neuroimaging techniques. Hypercapnia leads to an increase in CBF while neural activity remains unaffected. Laser Doppler (LD) flowmetry was used to measure CBF changes (LD(CBF)) in the somatosensory cortex due to periodic electrical forepaw stimulation (4 s in duration) before and during graded hypercapnia (3% CO(2), 5% CO(2) and 10% CO(2)). With increasing CO(2) concentrations, the baseline LD(CBF) progressively increased. The peak height (PH) of the LD(CBF) response, expressed as a percent change from the observed baseline for each hypercapnic state, significantly decreased (P<0.05) with increasing CO(2) concentrations. However, the absolute magnitude of the LD(CBF) change was independent of CO(2) concentration. The temporal dynamics of the LD(CBF) response during hypercapnia were significantly prolonged compared to baseline conditions (P<0.05).     

Changes in cortical microvasculature during misery perfusion measured by two-photon laser scanning microscopy

This study aimed to examine the cortical microvessel diameter response to hypercapnia in misery perfusion using two-photon laser scanning microscopy (TPLSM). We evaluated whether the vascular response to hypercapnia could represent the cerebrovascular reserve. Cerebral blood flow (CBF) during normocapnia and hypercapnia was measured by laser-Doppler flowmetry through cranial windows in awake C57/BL6 mice before and at 1, 7, 14, and 28 days after unilateral common carotid artery occlusion (UCCAO). Diameters of the cortical microvessels during normocapnia and hypercapnia were also measured by TPLSM. Cerebral blood flow and the vascular response to hypercapnia were decreased after UCCAO. Before UCCAO, vasodilation during hypercapnia was found primarily in arterioles (22.9%±3.5%). At 14 days after UCCAO, arterioles, capillaries, and venules were autoregulatorily dilated by 79.5%±19.7%, 57.2%±32.3%, and 32.0%±10.8%, respectively. At the same time, the diameter response to hypercapnia in arterioles was significantly decreased to 1.9%±1.5%. A significant negative correlation was observed between autoregulatory vasodilation and the diameter response to hypercapnia in arterioles. Our findings indicate that arterioles play main roles in both autoregulatory vasodilation and hypercapnic vasodilation, and that the vascular response to hypercapnia can be used to estimate the cerebrovascular reserve.     

Effects of topical adenosine analogs and forskolin on rat pial arterioles in vivo

We utilized the closed window technique to study the in vivo responses of rat pial arterioles to superfused adenosine agonists. Adenosine and its analogs dilated pial arterioles and exhibited the following order of potency: 5'N-ethylcarboxamide adenosine (NECA) greater than 2-chloroadenosine (2-CADO) greater than adenosine = R-N6-phenylisopropyladenosine (R-PIA) = S-PIA greater than N6-cyclohexyladenosine (CHA). This potency profile suggests that cerebral vasodilation is mediated through the A2 receptor. Forskolin (10(-9) M) potentiated the vasodilation caused by 10(-6) M NECA, thus implicating adenylate cyclase activation during NECA-induced vasodilation and providing further support for involvement of the A2 receptor.     

Nociceptin/orphanin FQ contributes to hypoxic/ischemic impairment of hypercapnic cerebrovasodilation

Previous studies in piglets show that hypercapnic pial artery dilation was blunted following cerebral ischemia. Unrelated studies show that the newly described opioid nociceptin orphanin FQ (NOC/oFQ) is released into cerebrospinal fluid and contributes to altered cerebral hemodynamics following hypoxia/ischemia. This study was designed to determine the contribution of NOC/oFQ to hypoxic/ischemic impairment of hypercapnic pial dilation in piglets equipped with a closed cranial window. Global cerebral ischemia was produced via elevated intracranial pressure. Hypoxia decreased P(O2) to 34 +/- 3 mmHg. Topical NOC/oFQ (10(-10) M), the CSF concentration following hypoxia/ischemia, had no effect on pial artery diameter by itself but attenuated hypercapnia P(CO2) of (73 +/- 2 mmHg)-induced pial artery dilation (28 +/- 2 vs. 19 +/- 2%). Hypercapnia pial artery dilation was blunted by hypoxia/ischemia but such dilation was partially protected by pretreatment with the putative NOC/oFQ receptor antagonist, [F/G] NOC/oFQ (1-13) NH(2) (10(-6) M), (25 +/- 1, sham control; 4 +/- 1, hypoxia/ischemia; and 12 +/- 3%, hypoxia/ischemia + [F/G] NOC/oFQ (1-13) NH(2), respectively). These data suggest that NOC/oFQ release contributes to impaired hypercapnia-induced cerebrovasodilation following hypoxia/ischemia.     

Evidence against parenchymal metabolites directly promoting pial arteriolar dilation during cortical spreading depression in rabbits

The role of parenchymal metabolic factors in directly promoting pial arteriolar dilation during cortical spreading depression (CSD) in anesthetized rabbits was examined by direct measurement of periarachnoid cerebrospinal fluid (CSF) levels of a representative metabolite (i.e., K+) or superfusion of the cerebral cortical surface with artificial CSF. CSD was induced by KCl microinjection or tissue puncture and its movement was monitored electrophysiologically. Pial arteriolar diameter was determined using a closed cranial window and intravital microscopy. CSD propagated across the cortex under the window with a velocity of 2.9 +/- 0.2 mm/min, and caused pial arteriolar diameter to increase from 87 +/- 9 microns to 133 +/- 11 microns (53%, n = 23) for 1.6 +/- 0.1 min. At the same time, K+ concentration increased from 3.0 +/- 0.2 mM to a maximum of 4.6 +/- 0.3 mM. Topical application of 6 mM K+ increased pial arteriolar diameter by only 8%. Continuous superfusion of the cortical surface with aCSF at a rate of 3.0-4.5 ml/min (window volume = 0.5 ml) did not affect pial arteriolar dilation during CSD, but virtually abolished pial arteriolar dilation during inhalation of 10.2% CO2. These results suggest that pial arterioles dilate via a mechanism which does not involve diffusion of vasoactive metabolites released from the parenchyma during CSD.     

L-arginine partially restores the diminished CO2 reactivity after mild controlled cortical impact injury in the adult rat.

Using an open cranial window technique, the authors investigated the mechanisms associated with the suppressed CO2 reactivity after mild controlled cortical impact (CCI) injury in rats. The dilation of arterioles (n = 7) to hypercapnia before injury was 38 +/- 12%, which was significantly reduced both at 1 hour (23 +/- 15% dilation) and at 2 hours after injury (11 +/- 19% dilation). In the presence of L-arginine (10 mmol/L topical suffusion, 300 mg/kg intravenous infusion), the dilation of pial arterioles (n = 6) to hypercapnia was partially restored to 30 +/- 6% at 2 hours after injury. In the presence of the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP) (10(-8) mol/L topical suffusion), the dilation of pial arterioles (n = 5) to hypercapnia remained diminished (5 +/- 7%) at 2 hours after injury. The dilation of pial arterioles (n = 4) to hypercapnia also remained suppressed (5 +/- 6%) with topical suffusion of the free radical scavengers, polyethylene glycol-superoxide dismutase (60 units/mL) and polyethylene glycol-catalase (40 units/mL). The authors have shown that L-arginine at least partially restores the diminished response to hypercapnia after mild CCI injury. Furthermore, these data suggest that the beneficial effects of L-arginine are mediated by a combination of providing substrate for NO synthase and scavenging free radicals.     

Regional cerebral blood flow during hypercapnia in the anesthetized rabbit

These experiments were designed to test the hypothesis that increases in blood flow to the lower brainstem would be greater than forebrain regions during arterial hypercapnia. Total and regional cerebral blood flow (CBF) was measured via the tracer microsphere technique in seven anesthetized New Zealand white rabbits during normocapnia (arterial PCO2 congruent to 40 torr) and hypercapnia (arterial PCO2 congruent to 80 torr). During normocapnia average CBF was 0.77 ml/min/g, and regional measurements of blood flow indicated significantly greater flow to the cerebrum (0.86 ml/min/g) than either the medulla (0.52 ml/min/g) or the pons (0.49 ml/min/g). When arterial PCO2 was increased average CBF increased 113%, and a significant linear regression was calculated for arterial PCO2 vs CBF [CBF (ml/min/g) = 0.028 PCO2 (torr) - 0.502]. The distribution of blood flow within the brain was similar to normocapnia except that blood flow to the cerebellum was now greater than any other brain region (1.97 ml/min/g for the cerebellum compared to 1.66 ml/min/g for the cerebrum). Absolute increases in blood flow to the lower brainstem were equal to or less than other areas of the brain. We conclude that ponto-medullary blood flow does not increase disproportionate to other areas of the brain during hypercapnia, but some redistribution of CBF does occur in that cerebellar blood flow increased significantly more than the cerebrum, medulla, or pons.     

Reaction of pial arteries and veins to hypercapnia in hypertensive and normotensive rats

The lumen diameters of the main cortical surface arteries were continuously monitored through a closed cranial window in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The arterial diameter was significantly smaller in SHR (55 +/- 1 micron) than in WKY (87 +/- 1 micron) during resting conditions as well as during hypercapnic dilatation (87 +/- 2 micron compared to 117 +/- 5 micron). The per cent increase in diameter induced by hypercapnia was larger in SHR (54%) than in WKY (36%), presumably a consequence of the altered vascular wall to lumen ratio. Alpha-adrenoreceptor blockade with yohimbine and phenoxybenzamine had no significant effect on arterial diameter during hypercapnia. The diameters of the largest pial surface veins increased to the same extent in SHR and WKY during hypercapnia (about 10%).     

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).     

Cerebral blood flow reactivity to changes in carbon dioxide calculated using end-tidal versus arterial tensions

We retrospectively examined arerial and end-tidal estimations of CO2 tension used to calculate cerebrovascular reactivity in 68 anesthetized patients. CBF was measured using the intravenous 133Xe technique at mean +/- SD PaCO2 values of 28.2 +/- 5.2 and 38.8 +/- 4.8 mm Hg. The correlation between all PaCO2 and end-tidal PCO2 (PetCO2) values was y = 0.85x - 0.49 (r = 0.93, p = 0.0001). There was a moderate correlation between age and the difference between PaCO2 and PetCO2 (y = 0.11x + 0.79; r = 0.73, p = 0.0001). Cerebrovascular reactivity to changes in CO2 (ml 100 g-1 min-1 mm Hg-1) was similar (p = 0.358) when calculated by using either PaCO2 (1.9 +/- 0.8) or PetCO2 (1.8 +/- 0.8) and highly correlated (y = 0.86x + 0.23; r = 0.91, p = 0.0001). The CBF response to changes in CO2 tension can be reliably estimated from noninvasive measurement of PetCO2.