Renal hemodynamic effect of angiotensin II type 2 receptor

In the present study, the role of the angiotensin II type 2 receptor in the regulation of medullary blood flow in conscious Spontaneous Hypertensive Rats(SHR) was investigated. We tested the hypothesis that AT2 receptor activation may exert the opposite effects of AT1 receptors in terms of renal hemodynamics. Mean arterial pressure(MAP), daily sodium balance, cortical blood flow(CBF), and medullary blood flow(MBF) were measured over a 10-day protocol in several groups of rats in which optical fibers for laser-Doppler flowmetry had been implanted and which received the following drug combinations: the AT1 receptor antagonist CV11976(CV) alone and CV plus AT2 receptor antagonist PD123319 (PD). In the CV alone group, the renal interstitial administration of CV decreased MAP, caused sodium diuresis, and increased MBF significantly. In the CV plus PD group, the renal interstitial administration of PD prevented sustained hypotension, sodium diuresis, and increased medullary blood flow during CV administration. These data indicated that AT2 receptor activation leads to vasodilation in the renal medulla and an antihypertensive effect in SHR. AT2 receptors play an important role in the renal medullary blood flow.     

Coerced training of the nondominant hand resulting in cortical reorganization: a high-field functional magnetic resonance imaging study

OBJECT: The authors investigated brain strategies associated with hand use in an attempt to clarify genetic and nongenetic factors influencing handedness by using high-field functional magnetic resonance imaging. METHODS: Three groups of patients were studied. The first two groups comprised individuals in whom handedness developed spontaneously (right-handed and left-handed groups). The third group comprised individuals who were coercively trained to use the right hand and developed mixed handedness, referred to here as trained ambidexterity. All trained ambidextrous volunteers were certain that they were innately left-handed, but due to social pressure had modified their preferred hand use for certain tasks common to the right hand. Although right-handed and left-handed volunteers displayed virtually identical cortical activation, involving homologous cortex primarily located contralateral to the hand motion, trained ambidextrous volunteers exhibited a clearly unique activation pattern. During right-handed motion, motor areas in both hemispheres were activated in these volunteers. During left-handed motion, the right supplemental motor area and the right intermediate zone of the anterior cerebellar lobe were activated significantly more frequently than observed in naturally right-handed or left-handed volunteers. CONCLUSIONS: The results provide strong evidence that cortical organization of spontaneously developed right- and left-handedness involves homologous cortex primarily located contralateral to the hand motion, and this organization is likely to be prenatally determined. By contrast, coerced training of the nondominant hand during the early stages of an individual's development results in mixed handedness (trained ambidexterity), indicating cortical reorganization.     

异丙酚对健康志愿者局部脑血流的影响

目的 评价异丙酚对健康志愿者局部脑血流的影响,初步筛选其全麻作用的中枢靶位.方法 健康志愿者7名,性别不限,年龄24～34岁,体重50～69 kg,ASA Ⅰ级.志愿者随机静脉输注生理盐水4 mg·kg-1·h-1(清醒状态)、异丙酚妓应室靶浓度1.5 μg/ml(镇静状态)和3.0 μg/ml(意识消失状态),间隔至少48 h.静脉输注生理盐水10 min或达设定的效应室靶浓度后,稳定10 min,静脉注射99Tcm-双半胱乙酯0.5 mCi/kg,10 min后停止输注异丙酚使志愿者清醒,并在清醒后10 min内采用单光子发射断层扫描仪测定局部脑血流量(rCBF).结果 与清醒状态时比较,志愿者镇静状态时全脑CBF降低,大脑皮层rCBF降低(P<0.05),皮层下区rCBF差异无统计学差异(P>0.05),意识消失状态时全脑CBF、大脑皮层和皮层下区rCBF均降低(P<0.05);与镇静状态时比较,志愿者意识消失状态时小脑、顶叶、丘脑、扣带回、海马和额叶rCBF降低(P<0.05).3种状态下全脑CBF与BIS呈正相关(r=0.883,P<0.05).结论 异丙酚产生镇静效应时,健康志愿者大脑皮层rCBF降低,产生意识消失效应时大脑皮层区和皮层下区rCBF均降低,尤其是丘脑、海马、扣带回等区域,提示这些区域可能是异丙酚麻醉的中枢作用靶位.     

Outcome prediction within twelve hours after severe traumatic brain injury by quantitative cerebral blood flow

We measured quantitative cortical mantle cerebral blood flow (CBF) by stable xenon computed tomography (CT) within the first 12?h after severe traumatic brain injury (TBI) to determine whether neurologic outcome can be predicted by CBF stratification early after injury. Stable xenon CT was used for quantitative measurement of CBF (mL/100?g/min) in 22 cortical mantle regions stratified as follows: low (0-8), intermediate (9-30), normal (31-70), and hyperemic (>70) in 120 patients suffering severe (Glasgow Coma Scale [GCS] score ≤8) TBI. For each of these CBF strata, percentages of total cortical mantle volume were calculated. Outcomes were assessed by Glasgow Outcome Scale (GOS) score at discharge (DC), and 1, 3, and 6 months after discharge. Quantitative cortical mantle CBF differentiated GOS 1 and GOS 2 (dead or vegetative state) from GOS 3-5 (severely disabled to good recovery; p<0.001). Receiver operating characteristic (ROC) curve analysis for percent total normal plus hyperemic flow volume (TNHV) predicting GOS 3-5 outcome at 6 months for CBF measured <6 and <12?h after injury showed ROC area under the curve (AUC) cut-scores of 0.92 and 0.77, respectively. In multivariate analysis, percent TNHV is an independent predictor of GOS 3-5, with an odds ratio of 1.460 per 10 percentage point increase, as is initial GCS score (OR=1.090). The binary version of the Marshall CT score was an independent predictor of 6-month outcome, whereas age was not. These results suggest that quantitative cerebral cortical CBF measured within the first 6 and 12?h after TBI predicts 6-month outcome, which may be useful in guiding patient care and identifying patients for randomized clinical trials. A larger multicenter randomized clinical trial is indicated.     

The cerebrovascular effects of curare and histamine in the rat

The effects of histamine and curare on cerebral blood flow (CBF) were measured in rats with an intact blood-brain barrier (BBB) and in rats in which the BBB was disrupted by hypertonic urea. Using radioactive microspheres cortical and subcortical CBF were measured in paralyzed ventilated rats anesthetized with 70% N2O, 30% oxygen. Blood gas tensions were controlled by mechanical ventilation. In rats with an intact BBB, neither histamine infusion (10 micrograms X kg-1 X min-1) nor curare (1 and 5 mg/kg) increased CBF. Twenty minutes after the BBB was disrupted by 2 M urea, histamine (10 micrograms X kg-1 X min-1) produced an increase in cortical (180-210 ml X 100 g-1 X min-1) and subcortical CBF (103 to 124 ml X 10 g-1 X min-1). Twenty minutes after BBB disruption, curare also produced a significant increase in cortical CBF (1 mg/kg: 176-201 ml X 100 g-1 X min-1, 5 mg/kg: 190-209 ml X 100 g-1 X min-1). The increases in CBF produced by curare were completely blocked by pretreatment with 30 mg/kg cimetidine, a histamine H2 receptor antagonist, 3 min before curare. The results indicate that curare may produce cerebrovasodilation and increases in CBF by release of histamine and stimulation of central nervous system H2 receptors. These effects occur only when the BBB is disrupted and circulating histamine has access to brain perivascular tissue.     

Brain blood flow and metabolism do not decrease at stable brain temperature during cardiopulmonary bypass in rabbits.

Cerebral blood flow (CBF) during human hypothermic cardiopulmonary bypass has been reported to decrease with time, suggesting that progressive cerebral vasoconstriction or embolic obstruction may occur. We tested the hypotheses: 1) that observed CBF reductions were due to continued undetected brain cooling and 2) that CBF during cardiopulmonary bypass would be stable after achievement of constant brain temperature. Anesthetized New Zealand White rabbits underwent cardiopulmonary bypass (membrane oxygenator, centrifugal pump, bifemoral arterial perfusion) and were assigned to one of three bypass management groups based on perfusate temperature and PaCO2 management: group 1 (37 degrees C, n = 8); group 2 (27 degrees C, pH-stat, n = 9); and group 3 (27 degrees C, alpha-stat, n = 8). Systemic hemodynamics, and cerebral cortical, esophageal, and arterial perfusate temperatures were recorded every 10 min for the first hour of bypass and again at 90 min. CBF and masseter blood flow (radiolabeled microspheres) were determined at 30, 60, and 90 min of bypass, while the cerebral metabolic rate for oxygen (CMRO2) was determined at 60 and 90 min. Groups were comparable with respect to mean arterial pressure, central venous pressure, hematocrit, and arterial oxygen content throughout bypass. Cortical temperature was stable in normothermic (group 1) animals, and there was no significant change in CBF between 30 and 90 min of bypass: 68 +/- 18 versus 73 +/- 20 ml.100 g-1.min-1 (mean +/- SD). In the hypothermic groups (2 and 3), cortical temperature equilibration (95% of the total change) required 41 +/- 6 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective blockade of AT1 receptor attenuates impairment of hypotensive autoregulation and improves cerebral blood flow after brain injury in the newborn pig

BACKGROUND: Fluid percussion injury (FPI) in piglets produces vasoconstriction of pial arteries (PAs), decreases in cerebral blood flow (CBF), and impairment of hypotensive autoregulation. Two types of angiotensin II receptors, AT1 and AT2, have been identified in the brain. This study characterized the effect of pretreatment with AT1- and AT2-selective antagonists on CBF and hypotensive autoregulation after FPI. METHODS: Fluid percussion injury was induced in chloralose-anesthetized newborn pigs equipped with closed cranial windows. CBF was determined by the radiolabeled microsphere technique. RESULTS: Moderate and severe hypotension (71 +/- 3, 53 +/- 2, and 40 +/- 1 mmHg for normotension, moderate hypotension, and severe hypotension, respectively) elicited PA dilation without changes in CBF in sham control piglets. The AT1 antagonist ZD 7155 partially restored impaired hypotension-induced PA dilation after FPI (19 +/- 1 and 34 +/- 1 vs. 5 +/- 1 and 7 +/- 1 vs. 12 +/- 1 and 20 +/- 3% for PA dilation during moderate and severe hypotension in sham control, FPI, and FPI + ZD 7155 animals, respectively). ZD 7155 also blunted the reductions in CBF during normotension and hypotension observed in untreated animals (43 +/- 4, 38 +/- 5, and 55 +/- 3 vs. 32 +/- 4, 19 +/- 2, and 27 +/- 5% CBF reductions during normotension, moderate hypotension, and severe hypotension in untreated and pretreated animals, respectively). The AT2 selective antagonist PD 123,319 did not restore hypotension-induced PA dilation and did not prevent decreases in CBF observed during normotension and moderate and severe hypotension after FPI. CONCLUSION: These data indicate that blockade of the AT1 and not the AT2 receptor diminished the reduction in hypotensive PA dilation after FPI. AT1 blockade also blunted the decrease in CBF during normotension as well as the further decrease in CBF observed during hypotension after FPI. These data suggest that AT1 receptor activation by angiotensin II contributes to cerebrovascular dysregulation during hypotension after FPI.     

Effect of biflow-induced ventilation (BIFIV) on cerebral cortical blood flow in anesthesized rabbits with intracranial hypertension

This study compared the effect of biflow-induced ventilation (BIFIV) and conventional mechanical ventilation (CMV) on cerebral cortical blood flow (CBF) of six anaesthetized rabbits with an intracranial pressure (ICP) at 45 mmHg. BIFIV did not improve CBF during increased ICP when compared to CMV.     

Changes in cerebral blood flow from the acute to the chronic phase of severe head injury

We studied cerebral blood flow (CBF) in the transition from the acute to the chronic phase of severe head injury in order to determine patterns of change in relation to neurological outcome. We measured CBF with stable xenon-enhanced computed tomography (Xe-CT) in 20 consecutive patients at 1, 2, 3, 4, and 6 weeks after severe head injury, and analyzed the relation between the pattern of change in CBF and neurological outcome at 6 months after injury. CBF values were significantly lower in the brain-injured patients than in 14 healthy volunteers, except at 3 weeks after injury, when CBF increased in the patients to a value that did not differ significantly from that in the normal volunteers. We therefore focused on the change in CBF at 3 weeks after injury. We separated the 20 brain-injured patients into two subgroups, of which the first (subgroup A) consisted of nine patients whose CBF had returned to normal by week 3 post-injury, while the second (subgroup B) consisted of 11 patients whose CBF was subnormal at week 3 post-injury. CBF was significantly higher in subgroup A than in subgroup B at 2 weeks post-injury (p < 0.05). CBF in subgroup B remained significantly lower than that in subgroup A throughout the study period. At 6 months post-injury, subgroup A had a significantly better neurological outcome than did subgroup B (p < 0.05). We conclude that patients whose CBF returns to normal at 2-3 weeks following severe traumatic brain injury after being abnormally low in the acute phase of injury can be expected to achieve a good neurological outcome.     

Midazolam-ethanol interactions and reversal with a benzodiazepine antagonist

The purpose of these experiments was to analyze the cerebrovascular and cerebral metabolic effects of midazolam, a short-acting water-soluble benzodiazepine, and to investigate its interaction with alcohol in rats. A benzodiazepine antagonist, 3-carbo-t-butoxy-beta-carboline (beta-CCT), was used to test the role of the benzodiazepine receptor in midazolam-alcohol effects. Experiments were carried out under 70% N2O, 30% O2 anesthesia. Rats were tested with intraperitoneal injections of 0.75-5 mg/g ethanol, intravenous infusions of 0.57, 5.75 mg/kg midazolam, and 1.15 mg/kg beta-CCT separately and in combination. Cortical cerebral blood flow (CBF) was measured with radioactive microspheres, and cerebral oxygen consumption (CMRO2) was determined from cortical CBF and arterial-sagittal sinus blood samples 20 min after ethanol treatment and/or after a 15-min drug infusion. Alcohol alone produced dose-related increases in plasma ethanol concentrations but no depression in CMRO2 except at the highest dose (5 mg/g). Midazolam infusions alone decreased cortical CBF and CMRO2 35-40%, while 2.5 mg/g alcohol (which did not depress CMRO2 alone) combined with midazolam produced a 70% depression of cortical CBF and metabolism. An infusion of beta-CCT given alone increased CMRO2 alone and reversed the depression in both cortical CBF and CMRO2 produced by midazolam plus alcohol. These results indicate that the ability of alcohol to potentiate benzodiazepine-induced sedation is not simply an additive effect but may be related to the facilitation by alcohol of benzodiazepine receptor binding. The fact that beta-CCT reversed midazolam-ethanol-induced depression suggests that the effect may be mediated through the benzodiazepine receptor.     

Volume measurement of cerebral blood flow: assessment of cerebral circulatory arrest

BACKGROUND: Cerebral blood flow (CBF) volume can be measured at bedside by color duplex flowmetry of the extracranial cerebral arteries. In neurointensive care patients, we prospectively tested the hypothesis that a CBF volume <100 ml/min indicates imminent cerebral circulatory arrest. METHODS: CBF volume was determined as sum of flow volumes in the internal carotid and vertebral arteries of both sides. In 192 neurointensive care patients, 829 measurements were taken. When CBF volume fell short of 100 ml/min, common carotid and external carotid artery flow volumes were also measured, and transcranial color-coded duplex sonography (TCCD) of basal cerebral arteries was performed. Results were compared with actual clinical conditions, outcome, and previously published reference data. RESULTS: All 41 patients with CBF volume <100 ml/min (range, 0-89 ml/min) were officially declared brain dead 2-126 hours after the measurement (median, 23 hours). TCCD revealed signs of cerebral circulatory arrest in all patients with a patent acoustic bone window. External carotid artery flow volumes were normal. The lowest CBF volume rate recorded in a surviving patient was 208 ml/min. CONCLUSIONS: Early confirmation of cerebral circulatory arrest is of decisive importance if the patient is a potential organ donor. CBF volume measurement allows confirming the arrest of cerebral circulation even in patients without a patent acoustic bone window for TCCD. Because the critical lower threshold for survival appears to lie at 200 ml/min, bedside monitoring of CBF volume in neurointensive care patients may indicate a therapeutic window before irreversible circulatory arrest occurs.     

Regional cerebral blood flow responses to hyperventilation during sevoflurane anaesthesia studied with PET

Background: Arterial carbon dioxide tension (PaCO₂) is an important factor controlling cerebral blood flow (CBF) in neurosurgical patients. It is still unclear whether the hypocapnia‐induced decrease in CBF is a general effect on the brain or rather linked to specific brain regions. We evaluated the effects of hyperventilation on regional cerebral blood flow (rCBF) in healthy volunteers during sevoflurane anaesthesia measured with positron emission tomography (PET). Methods: Eight human volunteers were anaesthetized with sevoflurane 1 MAC, while exposed to hyperventilation. During 1 MAC sevoflurane at normocapnia and 1 MAC sevoflurane at hypocapnia, one H₂¹⁵O scan was performed. Statistical parametric maps and conventional regions of interest analysis were used for estimating rCBF differences. Results: Cardiovascular parameters were maintained constant over time. During hyperventilation, the mean PaCO₂ was decreased from 5.5 ± 0.7 to 3.8 ± 0.9 kPa. Total CBF decreased during the hypocapnic state by 44%. PET revealed wide variations in CBF between regions. The greatest values of vascular responses during hypocapnia were observed in the thalamus, medial occipitotemporal gyrus, cerebellum, precuneus, putamen and insula regions. The lowest values were observed in the superior parietal lobe, middle and inferior frontal gyrus, middle and inferior temporal gyrus and precentral gyrus. No increases in rCBF were observed. Conclusions: This study reports highly localized and specific changes in rCBF during hyperventilation in sevoflurane anaesthesia, with the most pronounced decreases in the sub cortical grey matter. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve during hypocapnia.     

The effect of suture pattern and tension on cutaneous blood flow as assessed by laser Doppler flowmetry in a pig model

OBJECTIVE: To determine the effects of various suture patterns on cutaneous blood flow (CBF) at the wound edge as increasing tension is applied through the suture. METHODS: Four different suture patterns commonly used for wound closure (simple, vertical mattress, horizontal mattress, and Allgower-Donati) were placed individually after a full-thickness incision was made in an anesthetized pig. A laser Doppler flowmeter (LDF) was placed on the skin edge after the suture was passed. Baseline CBF was recorded. Increasing tension was applied to the wound edge via the suture through a tensionometer in 0.5-lb (0.23-kg) increments from 0 to 2.5 lb (1.13 kg). CBF was then recorded as a function of tension for each suture pattern. RESULTS: The Allgower-Donati suture pattern affected CBF significantly less than the other three suture patterns did for all tensions from 0.5 to 2.0 lb (0-0.9 kg; P < 0.05). There were no significant differences between vertical mattress, horizontal mattress, and simple suture patterns. CONCLUSIONS: The Allgower-Donati suture pattern had the least effect on CBF with increasing tension in this model. Further study is warranted on the benefits of this suture pattern because it may decrease wound complications in traumatized tissues.     

Studies of experimental cervical spinal cord transection. Part III: Effects of acute cervical spinal cord transection on cerebral blood flow.

Regional cerebral blood flow (CBF) was measured by the microsphere technique in anesthetized, mechanically ventilated dogs before and after cervical laminectomy in four (control group), or cervical laminectomy followed by cervical cord transection (CCT) at the C-6 level in six (experimental group). No significant differences in arterial pH, pO2 or pCO2 were observed between control and experimental dogs. Baseline values for mean arterial pressure (MAP) were also similar in the two groups, but MAP fell in all experimental dogs after CCT (p less than 0.025). At 120 minutes after CCT, three of the six dogs had an MAP greater than 60 torr (66 +/- 4 torr), and in three the MAP was greater than 50 torr (45 +/- 3 torr). Regional CBF in cortical gray matter, white matter, and medulla did not change significantly after CCT in dogs with MAP greater than 60 torr. The CBF fell significantly at 120 minutes after CCT in all regions sampled in the dogs with MAP less than 50 torr (p less than 0.025). At 30 and 120 minutes after CCT, cerebellar blood flow fell significantly in all experimental animals (p less than 0.05). These findings indicate that, despite hypotension and sympathetic denervation of cerebral vessels, CBF in cortical gray matter, white matter, and medulla is maintained at normal levels after CCT by autoregulation as long as MAP exceeds 60 torr. Decreased cerebellar blood flow in the experimental group suggests redistribution of CBF after CCT with relative preservation of flow to gray matter, white matter, and medulla. Reduced CBF in the acutely cord-injured patient with significant hypotension (MAP less than 60 torr) may stimulate or complicate coexistent head injury.     

The effect of nitrous oxide on cortical cerebral blood flow during anesthesia with halothane and isoflurane, with and without morphine, in the rabbit

The effect of nitrous oxide on cortical cerebral blood flow (CBF) was examined during a varying background anesthetic state in the New Zealand White rabbit. Seventy percent nitrous oxide resulted in significant and similar increases in CBF during anesthesia with both 0.5 MAC of halothane (44 +/- 14 to 63 +/- 17 ml.100 g-1.min-1) (mean +/- SD) and anesthesia with isoflurane (34 +/- 9 to 41 +/- 11 ml.100 g-1.min-1). During anesthesia with 1.0 MAC halothane or isoflurane, N2O also increased CBF, but the increments (halothane, 73 +/- 34 to 111 +/- 54 ml.100 g-1 min-1; isoflurane 34 +/- 13 to 69 +/- 34 ml.100 g-1.min-1) were significantly greater than those observed at 0.5 MAC. When 0.5 MAC halothane or isoflurane was supplemented with morphine (10 mg/kg followed by an infusion of 2 mg.kg-1.min-1), the CBF effect of N2O was not significantly different from that observed with 0.5 MAC alone. It was concluded that, in the rabbit, the effects of N2O on cortical CBF vary with the background anesthetic state and that the increase in CBF caused by N2O becomes greater as the end-tidal concentration of halothane or isoflurane increases from 0.5 to 1.0 MAC. Morphine, when added to 0.5 MAC of halothane or isoflurane, does not alter the effect of 70% N2O on cortical CBF.     

The effects of PaCO2 on the cerebrovascular response to nitrous oxide in the halothane-anesthetized rabbit

Several authors have observed that nitrous oxide increases cerebral blood flow (CBF) and/or intracranial pressure (ICP) in experimental situations and in humans. However, the effects of hypocapnia on the cerebrovascular responses to N2O have not been investigated. Therefore, six New Zealand White rabbits were anesthetized with approximately equal to 1.0 MAC halothane (mean end-tidal concentration 1.26%) and surgically prepared for recording of ICP, the EEG, and both cortical and global CBF (by the H2-clearance method). After preparation was complete, measurements were obtained during ventilation with 70% nitrogen (in O2), and after the inspired gas mixture was changed to 70% N2O (still with 1.0 MAC halothane). Two such data pairs (N2-N2O) were obtained, one during hypocarbia (PaCO2 approximately equal to 20 mm Hg) and the other during normocarbic (PaCO2 approximately equal to 40 mm Hg) conditions. Mean arterial pressure (MABP) was held constant within each data pair by infusing angiotensin II as needed. Nitrous oxide resulted in a consistent increase in EEG frequency and decrease in amplitude as compared with N2, and produced small (approximately equal to 1 mm Hg) but statistically significant increases in ICP during both hypo- and normocarbic conditions. Nitrous oxide administration also increased CBF as measured both in frontal cortex and globally, with similar changes seen during hypo- and normocarbic conditions, e.g., cortical CBF increased from 42 +/- 8 to 59 +/- 15 ml.100 gm-1.min-1 during hypocarbia, and from 61 +/- 13 to 75 +/- 15 ml.100 gm-1.min-1 during normocarbia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ketanserin on cerebral blood flow autoregulation in healthy volunteers

Summary The effect of a clinically relevant dose of ketanserin (10 mg as a bolus followed by an infusion of 6mg/h) on cerebral blood flow (CBF) and CBF autoregulation was examined in 12 healthy volunteers. Changes in CBF were estimated by the cerebral arteriovenous-oxygen saturation difference method, while mean arterial blood pressure (MABP) was increased by norepinephrine and decreased by ganglionic blockade (trimethaphan camphosulphonate) combined with lower body negative pressure one hour after the infusion of ketanserin. During ketanserin infusion, MABP fell insignificantly by 2.5 mmHg (6 to –2), while CBF rose insignificantly by 5 ml/100 g/min. Autoregulation was preserved in all volunteers. CO₂-correction factors from 0 to 4.6% CBF/0.1 kPa were used. The lower limit of CBF autoregulation was 82 mmHg (80–86) with an SE of 3 mmHg (1–5) similar to a previous control group of healthy volunteers. Aside from a major decrease in MABP in one subject, no adverse side effects were observed.The present study shows that CBF autoregulation is maintained during ketanserin infusion.     

Reduced regional and global cerebral blood flow during fenoldopam-induced hypotension in volunteers.

Dopamine has a wide spectrum of receptor and pharmacologic actions that may affect cerebral blood flow (CBF). A new, selective dopamine-1 agonist, fenoldopam, is a potent systemic vasodilator with moderate alpha(2)-receptor affinity. However, the effects of fenoldopam on the cerebral circulation are undefined. We therefore hypothesized that infusion of fenoldopam would decrease mean arterial blood pressure (MAP) and might concurrently decrease CBF via vascular alpha(2)-adrenoreceptor activation in awake volunteers. We studied nine healthy normotensive subjects, using positron emission tomography to measure CBF in multiple cortical and subcortical regions of interest. In addition, bioimpedance cardiac output and middle cerebral artery blood flow velocity were determined during fenoldopam-induced hypotension. Three men and four women, aged 25-43 yr, completed the study. Fenoldopam infused at 1.3 +/- 0.4 microg. kg(-1). min(-1) (mean +/- SD) reduced MAP 16% from baseline: from 94 (89-100) mm Hg (mean [95% confidence interval]) to 79 [74-85] mm Hg (P < 0.0001). During the fenoldopam infusion, both cardiac output (+39%), and heart rate (+45%) increased significantly, whereas global CBF decreased from baseline, 45.6 [35.6-58.5] mL. 100 g(-1). min(-1), to 37.7 [33.9-42.0] mL. 100 g(-1). min(-1) (P < 0.0001). Despite restoration of baseline MAP with a concurrent infusion of phenylephrine, global CBF remained decreased relative to baseline values at 37.9 [34.0-42.3] mL. 100 gm(-1). min(-1) (P < 0.0001). Changes in middle cerebral artery velocity did not correlate with positron emission tomography-measured changes of CBF induced by fenoldopam, with or without concurrent phenylephrine. Implications: In awake volunteers with (presumably) intact cerebral autoregulation,fenoldopam-induced hypotension significantly decreased global cerebral bloodflow (CBF). Clinicians should be aware of these pharmacodynamic effects when choosing a vasodilator to control blood pressure, especially in situations where control of CBF, cerebral blood volume, and intracranial pressure are therapeutic priorities.     

Atraumatic measurement of cerebral blood flow in spontaneous meningeal hemorrhage

Cerebral blood flow (CBF) was measured 74 times in 50 patients with spontaneous meningeal hemorrhage using a method involving the inhalation of Xenon-133. The procedure is non-invasive, reproductible, and provides reliable results. Correlation was found between the clinical state and the CBF, but very low mean values for CBF, and ischemic foci associated with these values, were detected in cases where this could not be predicted from the clinical findings. No correlation existed between vasospasm seen on angiography and the ischemic foci revealed by the isotopic method. The age of patients had an influence on CBF values but not on the clinical course. Mean CBF levels during the first two weeks of the disease were significantly higher in patients in whom the course was uncomplicated, whatever their clinical condition (excluding coma) at the time of CBF measurement. A figure of 60 ml/100 g/min for gray substance blood flow appeared to be a threshold value, below which there was a greater risk of complications. Inversely, the outcome was favorable in all cases with a cortical blood flow superior to 70 ml. These findings suggest that cerebral blood flow measurement provides prognostic information which could be of marked assistance when deciding on appropriate therapy in such cases.     

Cerebral blood flow in subarachnoid hemorrhage: analysis in patients with poor outcomes

Cerebral blood flow (CBF) of 6 patients with poor outcome after subarachnoid hemorrhage is analyzed. Neurological grades of these patients were grade III in 2 and grade IV in 4 patients, and subarachnoid hemorrhage on CT was diffuse and thick in all patients. Cerebral blood flow was continuously measured for 7 to 19 days by the thermal diffusion flow probe with a peltier stack which was left on the cerebral cortex at the surgery for ruptured aneurysm. Moreover, CBF studies by cold xenon CT and 133Xe inhalation methods were also performed in discussing cases. At the same time intracranial pressure was monitored. Cerebral angiography was carried out in all except for 2 patients who died due to severe cerebral vasospasm. The initial CBF value of all patients was 20 to 40 ml/100 g/min (mean value: 27 ml/100 g/min), and these were significantly low compared to normal value (50 ml/100 g/min). Moreover, these CBF was substantially decreased several days after surgery in all patients, and it was marked in 3 patients who died. From these results it was clear that the degree of vasospasm is important to determine the prognosis. One of 3 patients who died had ruptured left posterior cerebral artery aneurysm with occlusion of bilateral internal carotid arteries. In this case further decrease of CBF due to vasospasm was observed in addition to low initial CBF resulting diffuse low flow in both hemispheres although extracranial to intracranial bypass was performed. On the other hand, it was also shown that the intracranial pressure was an important factor to influence the outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)