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Biomedical subjects

A W Gelb

Publications and source records attributed to A W Gelb.

At least 19 recordsLinked to original sources
PubMed2003

Circulating norepinephrine and cerebrovascular control in conscious humans.

BACKGROUND: Cerebral vasoconstriction without concurrent changes in systemic arterial blood pressure has been observed in both normal individuals and those with idiopathic orthostatic intolerance following several minutes of postural stress when circulating catecholamines are elevated. Therefore, we tested the hypothesis that alpha-adrenergic activation with and without elevated circulating norepinephrine (NE) directly affects cerebrovascular tone in healthy individuals. METHODS: Mean arterial pressure (MAP; tonometry) and cerebral blood flow velocity (MFV) in the middle cerebral artery (transcranial Doppler) were measured in seven healthy individuals during 15 min periods of saline and of 50 (low NE) and 100 (high NE) ng kg(-1) min(-1) infusions of NE. Following this, phentolamine (PHO) was administered to return MAP back to baseline while high NE infusion continued (high NE+PHO). Finally, NE infusion was stopped allowing the persistent effects of PHO to dominate. RESULTS: Circulating NE caused a dose-dependent increase in MAP (P<0.05). During combined high NE+PHO, blood pressure was initially reduced to baseline levels but then increased a second time (P<0.05) during the final approximately 5 min of this phase. MFV remained constant during both low NE and high NE. In contrast, the secondary increase in BP during the late high NE+PHO phase was associated with elevated MFV. Cerebral vascular resistance (CVR) increased during high NE but was reduced to baseline during both early and late portions of the combined high NE+PHO phase (i.e. despite the late-phase increase in blood pressure). CONCLUSIONS: The increase in CVR during NE infusion was explained by an autoregulatory response to the increased blood pressure and not an alpha-mediated constriction. However, PHO appeared to interfere with the normal autoregulatory response to increasing blood pressure.

Adult↗
PubMed2003

Detection of awareness in surgical patients with EEG-based indices--bispectral index and patient state index.

BACKGROUND: Patient state index (PSI) and bispectral index (BIS) are values derived from the EEG, which can measure the hypnotic component of anaesthesia. We measured the ability of PSI and BIS to distinguish consciousness from unconsciousness during induction and emergence from anaesthesia and a period of awareness in surgical patients. METHODS: Forty unpremedicated patients were randomized to receive: (1) sevoflurane/remifentanil (< or =0.1 microg kg(-1) min(-1)), (2) sevoflurane/remifentanil (> or = 0.2 microg kg(-1) min(-1)), (3) propofol/remifentanil (< or =0.1 microg kg(-1) min(-1)), (4) propofol/remifentanil (> or = 0.2 microg kg(-1) min(-1)). Every 30 s after the start of the remifentanil, patients were asked to squeeze the investigator's hand. Sevoflurane or propofol were given until loss of consciousness (LOC1). Tunstall's isolated forearm technique was used during neuromuscular block with succinylcholine. After tracheal intubation, propofol or sevoflurane were stopped until return of consciousness (ROC1). Propofol or sevoflurane were re-started to induce LOC2. After surgery, drugs were discontinued and recovery (ROC2) was observed. PSI and BIS at LOC (LOC1 and LOC2) were compared with those at ROC (ROC1 and ROC2) (t-test). Prediction probability (P(k)) was calculated from values at the last command before and at LOC and ROC. Values are mean (SD). RESULTS: At non-responsiveness, BIS (66 (17)) and PSI (55 (23)) were significantly less than at responsiveness (BIS, 79 (14); PSI, 77 (18); P<0.05). The wide variation with both BIS and PSI measurements of the 80 'awareness' values led to an erroneous classification as unconscious in some cases (BIS, six patients; PSI, nine patients). P(k) was 0.68 (0.03) (BIS) and 0.69 (0.03) (PSI). CONCLUSIONS: Despite significant differences between mean values at responsiveness and non-responsiveness for BIS and PSI, neither measure may be sufficient to detect awareness in an individual patient, reflected by a P(k) less than below 70%.

Adult↗
PubMed2001

Monitoring cerebral perfusion after subarachnoid hemorrhage using CT.

The aim of this prospective study was to assess the feasibility and diagnostic relevance of repetitive dynamic (contrast-enhanced) CT measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) in the first 3 weeks after aneurysmal subarachnoid hemorrhage (SAH). In 15 patients with SAH, 59 dynamic CT studies including 944 regions of interest (ROI) were analyzed. The results were correlated with the clinical course and time after the event and the occurrence of vasospasm. Values for the entire series were 33.8+/-19.3 ml/100 g/min (CBF), 3.3+/-1.3 ml/100 g (CBV), and 7.3+/-3.9 s (MTT). Significant differences in CBF and CBV were found between ROI in grey and white matter, with time after the event, between patients with significant and absent or minor vasospasm, and between patients with and without a presumed vasospasm-related infarct.

Cerebrovascular Circulation↗
PubMed2001

The effects of propofol in the area postrema of rats.

UNLABELLED: Propofol has an antiemetic effect that may be mediated by gamma-aminobutyric acid (GABA) influences on the serotonin system, the mechanism of which is not known. We used three techniques, immunohistochemistry, High Performance Liquid Chromatography, and electrophysiology, to define propofol's effects on the rat's brainstem. Paired male Wistar rats received propofol, 20 mg/kg/hr, or Intralipid for 6 h. The brains were then subjected to immunohistochemical analysis of serotonin. In a separate experiment after a propofol or Intralipid infusion, cerebrospinal fluid (CSF) was extracted from the fourth ventricle and analyzed for the amount of serotonin and 5-hydroxyindoleacetic acid. Electrophysiological neuronal recordings were made in the area postrema (AP) in response to propofol with and without a GABA or serotonin antagonist. Results showed that immunohistochemical staining for serotonin in the propofol rats was significantly increased (28 +/- 12%) in the dorsal raphe and decreased in the AP (17 +/- 6%) compared with control. There were no significant changes in the isoflurane-anesthetized animals. Both serotonin and 5-hydroxyindoleacetic acid in the CSF of the fourth ventricle at the level of the AP were significantly reduced by 63% and 36%, respectively. Both propofol and pentobarbital injections reduce AP neuronal activity, but only the propofol response was blocked by bicuculline, a GABA antagonist. We conclude that the reduced levels of serotonin in the AP and the CSF may explain the antiemetic property of propofol. Propofol may also directly act on AP neurons via a GABA(A) receptor to reduce their activity. IMPLICATIONS: Propofol may produce its antiemetic effect by depleting the area postrema of serotonin as well as by a direct gamma-aminobutyric acid-mediated inhibition.

Anesthetics, Intravenous↗
PubMed2001

Propofol protection of sodium-hydrogen exchange activity sustains glutamate uptake during oxidative stress.

UNLABELLED: We investigated the role of intracellular pH in protection by propofol of glutamate uptake during oxidative stress. Exposure of primary astrocyte cultures to tert-butylhydroperoxide (t-BOOH, 300 microM) decreased the initial rate of Na-dependent glutamate uptake. Either propofol or alpha-tocopherol, administered 30 min after t-BOOH, attenuated this transport inhibition. These lipophilic antioxidants protected glutamate uptake whether the medium contained 25 mM bicarbonate or was nominally bicarbonate-free. t-BOOH also inhibited Na/H exchanger isoform 1 (NHE1) activation by intracellular protons and propofol prevented this inhibition. Blockade of NHE1 by the potent antagonist, 5-(N-ethyl-N-isopropyl) amiloride (1 microM), abolished the protective effects of small concentrations of propofol (1 microM) and alpha-tocopherol (40 microM) on glutamate uptake during oxidative stress in bicarbonate-free medium. 5-(N-ethyl-N-isopropyl) amiloride had no effect on antioxidant rescue of glutamate transport in medium containing 25 mM bicarbonate. These results indicate that regulation of intracellular pH may contribute to neuroprotection by propofol and other lipophilic antioxidants. Propofol concentrations that are associated with anesthesia and neuroprotection may prevent intracellular acidification during oxidative stress by preserving the NHE1 response to cytosolic protons. However, if intracellular acidification occurs nonetheless, then propofol protection of glutamate uptake activity becomes less effective and the extracellular glutamate concentration may increase to neurotoxic levels. IMPLICATIONS: Anesthetic concentrations of propofol maintain the capacity of brain cells to extrude protons during oxidative stress. However, if intracellular acidification occurs nonetheless, then propofol's protection of glutamate clearance mechanisms from oxidative damage becomes attenuated, and extracellular glutamate concentration may increase to neurotoxic levels.

Amiloride↗
PubMed2001

Anesthetic concentrations of propofol protect against oxidative stress in primary astrocyte cultures: comparison with hypothermia.

BACKGROUND: The extracellular concentration of glutamate in the brain increases after oxidative damage. This increase may be caused, in part, by changes in glutamate transport by astrocytes. The authors hypothesized that propofol and hypothermia mitigate the effects on astrocytes of oxidative stress. METHODS: Primary cultures of rat cerebral astrocytes were subjected to oxidative stress by incubation with tert-butyl hydroperoxide for 30 min, followed by a 30-90-min washout period. The effects of prophylactic (simultaneous with tert-butyl hydroperoxide application) and delayed (administered 30 min after the oxidant) propofol or hypothermia were determined by measuring the uptake of glutamate as well as the release of preloaded d-aspartate (a nonmetabolizable analog of glutamate) and endogenous lactate dehydrogenase (a cytosolic marker). RESULTS: Delayed administration of an anesthetic concentration of propofol (1-3 microm) prevented the inhibition of high-affinity glutamate uptake, stimulation of d-aspartate release, and increase in lactate dehydrogenase release caused by tert-butyl hydroperoxide (1 mm, 37 degrees C). The protective effect of propofol (EC50 = 2 microm) on glutamate uptake was 20-fold more potent than that of alpha-tocopherol (EC50 = 40 microm). Prophylactic hypothermia (28 and 33 degrees C) also protected astrocytes from tert-butyl hydroperoxide. Delayed hypothermia was not protective but did not compromise rescue by propofol. CONCLUSIONS: Clinical levels of propofol and hypothermia mitigate the effects of oxidative stress on astrocytic uptake and retention of glutamate, with propofol having a relatively larger therapeutic window. The ability of these treatments to normalize cell transport systems may attenuate the pathologic increase in extracellular glutamate at synapses and thus prevent excitotoxic neuronal death.

Anesthetics, Intravenous↗
PubMed2001

Perfusion mapping using computed tomography allows accurate prediction of cerebral infarction in experimental brain ischemia.

BACKGROUND AND PURPOSE: We have developed a dynamic CT method to measure absolute cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). In this study we evaluated the ability of CT-derived functional maps to detect infarction in a rabbit model of focal cerebral ischemia. METHODS: Sequential dynamic CT studies were performed at 2 different slices in 5 control rabbits and another 8 after induction of focal cerebral ischemia. The size of critically ischemic tissue was correlated to size of infarction measured by postmortem 2,3,5-triphenyltetrazolium chloride staining. In the control rabbits, short-term variability of the parameters was assessed by ANOVA analysis. RESULTS: In 7 of 8 animals of the ischemia group, cerebral infarction was visible on 2,3, 5-triphenyltetrazolium chloride staining, constituting 16.7+/-10.6% of the ipsilateral hemisphere. Good agreement of CBF functional maps with tissue specimens was found with respect to size and location of infarction. Best prediction of infarction was found for thresholds of CBF <10 mL/100 g per minute (mean size, 17.5+/-13.4%; r=0.95) and MTT >6 seconds (mean size, 15.6+/-13.5%; r=0.85), with regression slopes close to unity. CBV maps were less predictive of occurrence of infarction, especially in cases of small infarction. The short-term variability of CBF, CBV, and MTT in the control group was 10.9%, 15.2%, and 19.9%, respectively. CONCLUSIONS: Functional CT measurements of absolute CBF and MTT early after onset of ischemia allow prediction of the size and location of cerebral infarction with good accuracy.

Animals↗
PubMed2000

Glutamate stimulates ascorbate transport by astrocytes.

The concentrations of glutamate and ascorbate in brain extracellular fluid increase following seizure activity, trauma and ischemia. Extracellular ascorbate concentration also rises following intracerebral glutamate injection. We hypothesized that glutamate triggers the release of ascorbate from astrocytes. We observed in primary cultures of rat cerebral astrocytes that glutamate increased ascorbate efflux significantly within 30 min. The half-maximal effective concentration of glutamate was 180+/-30 microM. Glutamate-stimulated efflux of ascorbate was attenuated by hypertonic media. 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid inhibited both Na(+)-dependent glutamate uptake and ascorbate efflux. Two other inhibitors of volume-sensitive organic anion channels (1, 9-dideoxyforskolin and 5-nitro-2-(3-phenylpropylamino) benzoic acid) did not slow glutamate uptake but prevented stimulation of ascorbate efflux. Glutamate also stimulated the uptake of ascorbate by ascorbate-depleted astrocytes. In contrast, glutamate uptake was not affected by intracellular ascorbate, thus ruling out a putative glutamate-ascorbate heteroexchange mechanism. These results are consistent with activation by glutamate of ascorbate-permeant channels in astrocytes.

Amino Acids↗
PubMed2000

Rate of change of cerebral blood flow velocity with hyperventilation during anesthesia in humans.

PURPOSE: Although it has been suggested that the rate at which the cerebral circulation responds to changes in PaCO2 is different with differing anesthetics, there have been no attempts to measure this. Transcranial Doppler allows the continuous measurement of cerebral blood flow velocity (CBFV) and any changes over time. Our aim was to compare the rate of change of CBFV when end-tidal CO2 (P(ET)CO2) was rapidly altered during halothane or isoflurane anesthesia. METHODS: Twenty-eight unpremedicated healthy patients were randomly assigned to receive air/O2 and either 1-1.5 MAC halothane or isoflurane as the primary anesthetic. After 15 min of steady state, P(ET)CO2 was rapidly reduced from 45 mm Hg to 30 mm Hg. CBFV and P(ET)CO2 were recorded every 30 sec for the next 10 min. RESULTS: The rate of change of normalized CBFV (delta CBFV vs. delta time) was more rapid in the isoflurane group (P <0.0001) especially in the initial few minutes. In all patients anesthetized with isoflurane, and in all but two patients anesthetized with halothane, the reduction in P(ET)CO2 produced a corresponding decrease in CBFV However, there were no differences in the magnitude of cerebrovascular CO2 reactivity (delta CBFV vs. delta P(ET)CO2) between the two groups. CONCLUSIONS: The rate of change of CBFV was faster in the isoflurane than in the halothane group especially in the initial few minutes. Indeed, for two patients in the halothane group Vmca did not change despite a change in P(ET)CO2. This may be of clinical importance when cerebrovascular tone needs to be changed rapidly.

Adult↗
PubMed2000

Anesthesia for temporal lobe epilepsy surgery.

Anesthetic considerations for temporal lobectomy for refractory epilepsy include ensuring a safe and comfortable perioperative experience for the patient, providing suitable operating conditions for the surgeon, avoiding interference with intraoperative electrocorticographic (ECoG) recordings and facilitating intraoperative functional cortical mapping, if performed. Providing the conditions that simultaneously meet these requirements, using general anesthesia or local anesthesia with sedation, remains a significant challenge for the neuroanesthetist. We review issues pertinent to the choice of anesthetic technique for these procedures.

Anesthesia↗
PubMed2000

Cerebral blood volume and blood flow at varying arterial carbon dioxide tension levels in rabbits during propofol anesthesia.

UNLABELLED: There are little data on the effects of propofol on cerebral blood volume (CBV). We studied the effects of changes in PaCO(2) on CBV and cerebral blood flow (CBF) during propofol anesthesia in eight New Zealand white rabbits. We also investigated the effects of propofol over time on CBV and CBF during normocapnia (control group). At normocapnia, the mean (+/- SD) CBV and CBF values were 2.41 +/- 0.68 mL/100 g and 56 +/- 28 mL/100 g/min, respectively,. When PaCO(2) was reduced from 41 to 27 mm Hg, no significant change in either CBV or CBF was observed (P > 0.10). However, increasing PaCO(2) from 41 to 58 mm Hg resulted in a 30% increase in CBV (3.08 +/- 0.86 mL/100 g, P < 0.05) and a 91% increase in CBF (97 +/- 39 mL/100 g/min, P < 0.01). In the control group, there were no significant changes in CBV and CBF (P > 0.10) during 2 h of propofol anesthesia. These results indicate that, during propofol anesthesia, cerebrovascular reactivity of blood flow and blood volume is maintained during hypercapnia but is markedly diminished during hypocapnia. IMPLICATIONS: During propofol anesthesia in rabbits with normal brains, a reduction in the arterial carbon dioxide level may not always be accompanied by a reduction in brain blood flow and blood volume.

Absorptiometry, Photon↗
PubMed2000

A CT method to measure hemodynamics in brain tumors: validation and application of cerebral blood flow maps.

BACKGROUND AND PURPOSE: CT is an imaging technique that is routinely used for evaluating brain tumors. Nonetheless, imaging often cannot show the distinction between radiation necrosis and neoplastic growth among patients with recurrent symptoms after radiation therapy. In such cases, a diagnostic tool that provides perfusion measurements with high anatomic detail would show the separation between necrotic areas, which are characterized by low perfusion, from neoplastic areas, which are characterized by elevated CBF. We attempted to validate a dynamic contrast-enhanced CT method for the measurement of regional CBF in brain tumors, and to apply this method by creating CBF maps. METHODS: We studied nine New Zealand White rabbits with implanted brain tumors. We obtained dynamic CT measurements of CBF, cerebral blood volume (CBV), and permeability surface (PS) from the tumor, peritumor, and contralateral normal tissue regions. In all nine rabbits (two studies per rabbit), we compared CT-derived CBF values with those simultaneously obtained by the standard of reference ex vivo microsphere technique. Using CT, we examined three rabbits to assess the variability of repeated CBF and CBV measurements; we examined the other six to evaluate regional CBF reactivity to arterial carbon dioxide tensions. Finally, CT CBF maps were obtained from a rabbit with a brain tumor during normocapnia and hypocapnia. RESULTS: We found a significant linear correlation (r = 0.847) between the regional CT-and microsphere-derived CBF values, with a slope not significantly different from unity (0.99+/-0.03, P>.01). The mean difference between regional CBF measurements obtained using both methods did not significantly deviate from zero (P>.10). During normocapnia, tumor had significantly higher CBF, CBV, and PS values (P<.05) than did peritumor and normal tissues. The variability in CT-derived CBF and CBV measurements in the repeated studies was 13% and 7%, respectively. CT revealed no significantly different CBF CO2 reactivity from that determined by the microsphere method (P>.10). The CBF map of tumor regions during normocapnia showed much higher flow than normal regions manifested, and this difference was reduced on the hypocapnia CBF map. CONCLUSION: The dynamic CT method presented herein provides absolute CBF measurements in brain tumors that are accurate and precise. Preliminary CBF maps derived with this method demonstrate their potential for depicting areas of different blood flow within tumors and surrounding tissue, indicating its possible use in the clinical setting.

Animals↗
PubMed1999

Rats show unimpaired learning within minutes after recovery from single bolus propofol anesthesia.

PURPOSE: To examine the learning ability of rats shortly after recovery from a bolus dose of propofol by assessing learning on a swim-to-platform task. Also, muscarinic blockade was used as a pharmacological test of whether learning shortly after propofol anesthesia resembles normal learning. METHODS: Propofol anesthetized rats (15-20 mg x kg(-1) i.v.) were trained on a swim-to-platform task five to seven minutes after recovering from surgical anesthesia and tested two to three hours later In addition, the muscarinic antagonist scopolamine hydrobromide (5 mg x kg(-1) s.c.) was given to a subgroup of rats before testing. During 10 trials, the number of times a given rat took 10 sec or longer to locate and climb onto a visible platform was tabulated and counted as errors. RESULTS: When trained shortly after recovery from the anesthetic, propofol anesthetized rats made 3.2 +/- 0.4 compared with 1.0 +/- 0.1 errors in controls (P < 0.0001). Two to three hours later both groups performed equally well. Rats trained after propofol anesthesia and given scopolamine before testing made 0.7 +/- 0.5 errors and performed as well as normal controls, 1.2 +/- 0.2 errors when subjected to the same procedures without propofol anesthesia, and better than scopolamine-treated untrained rats, 5.5 +/- 0.7 errors, (P < 0.05). CONCLUSION: Training five to seven minutes after recovery from propofol anesthesia resulted in normal retention of the swim- to-platform task. It also produced the same resistance to the disruptive effects of scopolamine as did training in rats that were not anesthetized. Thus, the ability to learn recovers rapidly after propofol anesthesia induced by a single intravenous bolus dose.

Anesthesia Recovery Period↗
PubMed1999

Cerebral blood volume measurements using dynamic contrast-enhanced x-ray computed tomography: application to isoflurane anaesthetic studies.

A convenient and simple method of measuring cerebral blood volume (CBV) will aid in the clinical management of patients with cerebrovascular diseases and head trauma. Using a two-compartment model to characterize the distribution of x-ray contrast agent in the brain, we have developed a non-equilibrium (dynamic) x-ray CT method to measure CBV and have applied this method to study the effects of isoflurane. CBV and cerebral blood flow (CBF, ex vivo) measurements were made in two groups of New Zealand White rabbits at varying (study group) and constant (control group) arterial CO2 concentration. ANOVA for repeated measures was used on the control data to determine the precision of our two-compartment CT-CBV method. The results showed that the precision of our CT-CBV measurement was 9.8%. In addition a paired t-test analysis of the control data revealed that the duration of isoflurane anaesthesia had no effect on the repeated measurements of CBV or CBF. The rate of change in CBV (0.049 ml/100 g/mmHg) and CBF (6.2 ml/min/100 g/mmHg) with respect to changes in arterial CO2 concentration under the influence of isoflurane anaesthesia was similar to those reported in previous studies, thus validating our experimental CT-CBV and CBF measurements. Our CT-CBV method will lead to more information on the relationship between CBV and CBF under different pharmacological interventions in both normal and disease conditions.

Analysis of Variance↗