JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chi, O. Z.
Right arrow Articles by Weiss, H. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chi, O. Z.
Right arrow Articles by Weiss, H. R.
Anesth Analg 1999;89:690
© 1999 International Anesthesia Research Society

NEUROSURGICAL ANESTHESIA

The Effects of Propranolol on Heterogeneity of Rat Cerebral Small Vein Oxygen Saturation

Oak Za Chi, MD*, Xia Liu, MD*, and Harvey R. Weiss, PhD{dagger}

Departments of *Anesthesia and {dagger}Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey

Address correspondence and reprint requests to Oak Za Chi, MD, Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 125 Paterson St., Ste. 3100, New Brunswick, NJ 08901-1977


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
ß-Adrenergic receptors are involved in altering cerebral metabolism and blood flow. This study was performed to determine whether propranolol would alter the microregional O2 balance in the brain. Rats were anesthetized with 1.4% isoflurane. Isotonic sodium chloride solution (control group), propranolol 2 mg/kg (low propranolol group) or propranolol 20 mg/kg (high propranolol group) was administered IV to the rats. Twenty minutes later, regional cerebral blood flow (rCBF) was measured using the 14C-iodoantipyrine autoradiographic technique. Small (diameter <70 µm) arterial and venous oxygen saturation (SaO2 and SvO2, respectively) was determined using microspectrophotometry in the alternate slices of the tissue sections used to measure rCBF. In both the low and high propranolol groups, average cortical rCBF was 35% lower than that in the control group. The average O2 consumption of the cortex of the propranolol groups was significantly lower than control (low propranolol: -41%, high propranolol: -49%). In all groups, SaO2 was almost identi-cal. The heterogeneity of the microregional SvO2 expressed as the coefficient of variation (CV = 100 x SD/mean) was significantly lower in the propranolol groups (low propranolol: 8.0 ± 2.3, high propranolol: 7.3 ± 2.9) than in the control group (13.4 ± 3.5). The proportion of cortical veins with SvO2 <55% was significantly smaller in the low and high propranolol groups (4 of 60 and 3 of 60, respectively) than that in the control group (15 of 60). In the other brain regions, the data followed a similar pattern. Our data demonstrated that propranolol is effective in decreasing O2 consumption, improving microregional O2 balance, and reducing its heterogeneity in the brain.

Implications: Our data suggest that the linkage of O2 supply and consumption is not tightly coupled under isoflurane anesthesia. ß-Adrenergic blockers may tighten this linkage and reduce the number of low O2-saturated microregions.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
The hypothesis that local neuronal activity of the brain will determine the local brain blood flow is generally accepted (1). Regional venous O2 saturation (SvO2) reflects the regional balance of O2 supply and consumption (2–4). If microregional cerebral blood flow matches its local O2 consumption precisely, the variation of local SvO2 would be minimal. However, studies suggest that the linkage between local cerebral blood flow and metabolism is not tightly coupled. A marked heterogeneous distribution of SvO2 and tissue O2 partial pressure has been demonstrated (2–7).

The mechanism of this heterogeneity of SvO2 is not known; however, one of the possible mechanisms could be via the sympathetic nervous system of the brain. Blocking peripheral sympathetic innervation of the cerebral blood vessels by bilateral cervical sympathectomy causes a significant decrease in the heterogeneity of microregional O2 saturation (7). ß-Adrenergic agonists have been reported to increase cerebral blood flow (CBF) and cerebral metabolic rate (CMR), especially when the blood-brain barrier (BBB) is disrupted (8–11).

We hypothesized that one of the factors that alters the heterogeneity of cerebral microregional O2 balance may involve ß-adrenergic receptors. We investigated whether blocking peripheral and central ß-adrenergic receptors could alter the heterogeneity of cerebral microregional O2 balance by affecting CMR, CBF, or both. In this experiment, propranolol, which crosses the BBB, was used to block ß-adrenergic receptors. Propranolol, a nonselective ß-adrenergic blocking drug, has no intrinsic sympathomimetic action but has a membrane-stabilizing activity (12). Propranolol decreases CBF and CMR and attenuates a cerebral vascular and metabolic response to catecholamines or some stresses (13–16). To determine CMR, most studies use a 2-deoxyglucose uptake technique, which measures the average rate of glucose use over a 45-min period. This technique fails to reflect instantaneous changes of CMR. In the present study, cryomicrospectrophotometry, which allows the determination of instantaneous changes of cerebral O2 consumption, was used to determine microscopic SaO2 and SvO2.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
This study was approved by our institutional animal care and use committee. Eighteen male Long-Evans rats (320–350 g) were divided into the following three groups of six rats each: 1) control group, 2) low propranolol group, and 3) high propranolol group. All rats were anesthetized with 1.4% isoflurane in an air and oxygen mixture (fraction of inspired oxygen 0.25–0.3), and their lungs were mechanically ventilated. A femoral artery and a femoral vein were catheterized. The femoral arterial catheter was connected to a Statham P23AA transducer (Gould Instruments, Cleveland, OH). Blood pressure was continuously monitored and recorded on a Beckman R-411 recorder (Fullerton, CA). Before determining regional cerebral blood flow (rCBF) or O2 consumption, a 0.2-mL arterial blood sample was withdrawn anaerobically and analyzed for PaO2, PaCO2, and pH using a blood gas analyzer (ABL330; Radiometer America, Westlake, OH). The hemoglobin concentration was measured using spectrophotometry. The femoral venous catheter was used to administer propranolol and radioactive tracers. Rectal temperature was monitored and maintained at 37°C by using a servocontrolled thermistor probe and a heating lamp. Pericranial temperature under the temporalis muscle was monitored using a thermocouple probe (Omega Engineering Inc., Stamford, CT) and was maintained at 37°C. For the low propranolol group, propranolol (Sigma, St. Louis, MO) 2 mg/kg was infused IV over a 1-min period, followed by isotonic sodium chloride solution administration. For the high propranolol group, propranolol 20 mg/kg was infused IV over a 10-min period. For the control group, the same volume of isotonic sodium chloride solution (approximately 2 mL) without propranolol was administered over a 10-min period.

Twenty minutes after the propranolol infusion, rCBF was measured using the 14C-iodoantipyrine quantitative autoradiographic technique modified from Sakurada et al. (17). Briefly, 50 µCi of 14C-iodoantipyrine was infused IV. When the isotope entered the venous circulation, the arterial catheter was cut to a length of 20 mm to minimize smearing in the sampling catheter. A 20-µL blood sample was obtained from the arterial catheter approximately every 3 s during the next 40 s. When the last sample was obtained, the animal was decapitated, and the head was frozen in liquid nitrogen. While frozen, tissue was sampled from the cortex, medulla, and putamen. These tissue samples were mounted with an embedding medium on a microtome cryostat at -35°C. Tissue slices of 20 µm thickness were obtained under a nitrogen atmosphere. Autoradiograms were prepared from these sections by exposure to radiograph film in radiograph cassettes for 5 days. The cerebral 14C tissue concentration was determined using a computer-based microdensitometer system and by reference to eight precalibrated standards (range 40–1069 µCi/g). For each brain region examined, a minimum of eight optical density measurements were made, each on a different section. Blood samples were placed in a tissue solubilizer; 24 h later, they were put in a counting fluid. These samples were counted on a liquid scintillation counter. The isotope counts were quench- corrected.

rCBF determinations were calculated using the equation described by Sakurada et al. (17).

Alternate slices of the tissue sections that were used to measure rCBF were used to determine SaO2 and SvO2. Details of this technique have been published previously (2–4,18). The tissue sections were transferred to precooled glass slides and covered with degassed silicone oil and a coverslip. These slides were placed on a microspectrophotometer fitted with a N2-flushed cold stage to obtain readings of optical densities at 523, 560, and 568 nm. This three-wavelength method corrects for light scattering in frozen blood. Only vessels in the transverse section were studied so that the path of light traversed only the blood. The size of the measuring spot was 8 µm in diameter. Readings were obtained to determine O2 saturation in the six to seven arteries and 9–10 veins (20–70 µm in diameter) found in these regions. The distribution of SvO2 was determined.

The O2 content of blood was determined by multiplying the percentage of O2 saturation by the hemoglobin concentration times 1.36. The difference between the average arterial and venous O2 contents (regional O2 extraction) was then obtained. Using the Fick principle, the paired product of O2 extraction and blood flow was obtained to determine the regional O2 consumption of the brain.

The coefficient of variation (CV) of SvO2 was used to compare changes in heterogeneity. The CV was calculated as 100 x SD/mean. A {chi}2 test was used to assess differences in the distribution of SvO2 and differences in the number of low saturated veins. A factorial analysis of variance was used to assess the differences among the groups and among the various examined regions for CBF, O2 balance variables, and the systemic hemodynamic and blood gas variables. Post hoc testing of multiple comparisons was performed using Duncan's procedure. All values were expressed as mean ± SD. Significance was defined as P < 0.05.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Hemodynamic and blood gas variables of the experimental groups are presented in Table 1. In the low propranolol group, the blood pressure was not significantly different from that of the control group. However, the heart rate was significantly lower than that of the control group (P < 0.05). In the high propranolol group, the systolic and mean blood pressures (P < 0.05) and the heart rate (P < 0.05) were significantly lower than those of the control animals. Blood gases and hemoglobin were similar in all groups.


View this table:
[in this window]
[in a new window]
  		Table 1. Hemodynamic and Blood Gas Values
 
rCBF values in the various regions of the brain of the three groups are presented in Figure 1. In the low propranolol group, the average rCBF of the cortex (P < 0.05) or medulla (P < 0.05) was significantly lower than that of the control group. In the putamen, however, the difference was not significant between these two groups. In the high propranolol group, the rCBF of all three brain regions was significantly lower than that of the corresponding brain region of the control group (cortex: P < 0.01, medulla: P < 0.005, putamen: P < 0.05). There was no statistical difference in rCBF or other O2 balance variables in each brain region between the low and high propranolol groups. There was no significant difference in rCBF or other O2 balance variables among the regions in any experimental group (Table 2, Figure 1).



View larger version (37K):
[in this window]
[in a new window]
  		Figure 1. Average regional cerebral blood flow of the experimental groups. *Significantly different from the control group.

 

View this table:
[in this window]
[in a new window]
  		Table 2. Regional O2 Balance Variables
 
In the low propranolol group, the average SvO2 of the cortex (P < 0.01) and the putamen (P < 0.01) was lower than that of the corresponding brain region of the control group. In the high propranolol group, in all of the brain regions studied (cortex: P < 0.01, medulla: P < 0.05, putamen: P < 0.05), the average SvO2 was lower than that of the corresponding control brain region (Table 2). The SaO2 was almost identical (91%–93%) in all regions of all groups.

The average O2 extraction in each brain region of the low propranolol group was not significantly different from that of the control group. In the high propranolol group, the O2 extraction in the cerebral cortex was lower than that of the control group (P < 0.05). In the other brain regions, the difference between these two groups was not significant (Table 2). In the low and high propranolol groups, the O2 consumption of each brain region (cortex: P < 0.005, medulla: P < 0.005, putamen: P < 0.01) that was examined was significantly lower than that of the corresponding brain region of the control group (Figure 2).



View larger version (33K):
[in this window]
[in a new window]
  		Figure 2. Average regional oxygen consumption of the experimental groups. *Significantly different from the control group.

 
The CV of SaO2 was 4.5–5.5 in all brain regions. The CV of SvO2 in the low (cortex: P < 0.05, medulla: P < 0.001, putamen: P < 0.005) and high propranolol groups (cortex: P < 0.01, medulla: P < 0.001, putamen: P < 0.001) in each brain region was significantly lower than that in the corresponding brain region of the control group (Table 2). The number of veins with O2 saturation <55% was significantly lower in the low (cortex: P < 0.01, medulla: P < 0.01, putamen: P < 0.01) and high propranolol groups (cortex: P < 0.005, medulla: P < 0.001, putamen: P < 0.0005) than in the control group in all brain regions studied. The percentage 55% was chosen because, in the control group, 25% of the veins had an O2 saturation <55% (Figure 3).



View larger version (17K):
[in this window]
[in a new window]
  		Figure 3. Distribution of microregional venous O2 saturation in the cortex of the experimental groups.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Our data demonstrate that a small (2 mg/kg) or large dose (20 mg/kg) of propranolol significantly decreases the heterogeneity of microregional SvO2 and decreases the number of veins with low O2 saturation in the three brain regions studied. Our data suggest that the heterogeneity of SvO2 may involve ß-adrenergic receptors. Propranolol decreased the average rCBF and the average O2 consumption in most of the brain regions studied, as previously reported (13–16).

Both CBF and CMR vary throughout the brain. The regional SvO2 reflects the regional balance of O2 supply and consumption because there is little variation in the regional SaO2 (2–4). Because a marked heterogeneous distribution of SvO2 and tissue O2 partial pressure has been reported, the linkage between CBF and CMR may not be tightly matched (2–7). It has been reported that various anesthetics exert various effects on the heterogeneity of SvO2 (2–4). Because every animal in the present study was anesthetized with the same concentration of isoflurane, the effects of anesthetics on the heterogeneity should be equal among the experimental animals.

The heterogeneity of cerebral microvascular SvO2 could be changed by the sympathetic nervous system of peripheral or central origin. There is evidence that cerebral arteries and arterioles are innervated by the adrenergic system and possess ß-adrenergic receptors (19–22). The peripheral sympathetic nervous system innervates the cerebral cortical area or blood vessels originating from the internal carotid artery (19). This innervation is heterogeneous. This heterogeneous distribution of the sympathetic innervation may limit flow and may decrease red cell velocity to certain microregional areas in the cerebral cortex without decreasing global CBF and rCBF. Thus, sympathetic innervation might be one of the factors responsible for the wide variations of cerebral cortical microvascular flow and red cell velocity that were observed by other investigators (6,23). Nonuniform reduction in blood flow and red cell velocity within the brain may increase O2 extraction within certain microregions, thereby broadening the heterogeneity of SvO2. Bilateral cervical sympathectomy causes no significant change in cortical O2 consumption and blood flow but results in a significant decrease in the heterogeneity of microregional SvO2 (7).

We hypothesized that blocking ß-adrenergic receptors could alter cerebral O2 supply and consumption balance in a microscopic area by affecting either microregional blood flow, neuronal metabolism, or both. Propranolol has been reported to decrease CBF and CMR and to attenuate the changes in CBF and CMR in response to various stressful stimuli (13–16). We speculated that propranolol might block not only the peripheral ß-adrenergic receptors, but also the central ß-adrenergic receptors because it crosses the BBB. We demonstrated that propranolol significantly decreases the average CBF and the average CMR under isoflurane anesthesia. In our study, propranolol was administered to animals already anesthetized with isoflurane. The cerebral metabolic and vascular responses to propranolol may be different in awake animals. In gently restrained awake rats, propranolol induces a small decrease in rCBF in some brain structures (15).

One of the reasons for this decrease of rCBF by propranolol could be its indirect action on blood flow through changes in the CMR. Changes in neuronal activity produced by stimulation or blockade of neuronal receptors associated with the cerebral central noradrenergic neurotransmitter system have been shown to change CMR (8,11,14,16). Because there is a close correlation between CMR and CBF, decreased CMR induced by the central ß-adrenergic receptor blockade would have decreased CBF through metabolically mediated vasoconstriction. Propranolol may have decreased metabolism in the metabolically active microregions and may have improved microregional O2 balance, resulting in a decreased heterogeneity of SvO2. In our study, the heterogeneity was significantly reduced (-40%) by propranolol. However, the average regional SvO2 was increased by only 5% with propranolol treatment. Our data suggest that, although propranolol slightly changed the average SvO2, it markedly altered the microregional O2 balance.

Another mechanism of decreased rCBF caused by propranolol could be due to a direct action on the cerebral vasculature through ß-adrenergic receptors in the arteries or arterioles, or due to an attenuation of the vasodilatory effect of isoflurane (19–22). Vascular ß-adrenergic receptors undergo rapid adaptation. They are probably less important than metabolically induced ß-adrenergic changes (24). This vasoconstrictive action may have not only decreased the overall CBF, but also reduced the microregional blood flow to the metabolically calm area. This may have helped the matching of blood flow and metabolism and may have subsequently lowered the number of veins with unnecessarily high O2 saturation in the present study, resulting in the decreased heterogeneity of SvO2. In this study, however, O2 extraction was not significantly altered when rCBF was reduced. Our study suggests that the primary action of propranolol in reducing rCBF is via decreasing the CMR, rather than via a direct action on the blood vessels.

Propranolol has a membrane-stabilizing activity, the so-called "local anesthetic-like effect." Because lidocaine, a local anesthetic, has been reported to decrease CBF and CMR, the local anesthetic-like effect of propranolol could have contributed to the decrease of rCBF, CMR, and heterogeneity of SvO2 (25).

In our study, the effects of blood pressure on CBF and the heterogeneity of O2 saturation should have been minimal because mean arterial blood pressure (MAP) was similar between the control and small-dose propranolol groups. In the large-dose propranolol group, despite relatively lower MAP, the rCBF and heterogeneity of SvO2 were not significantly different from those in the small-dose propranolol group. It is still possible that the decrease of rCBF in the propranolol-treated animals may be due to a decrease of cardiac output by propranolol. However, in our study, O2 extraction was not significantly altered or was only minimally altered with propranolol treatment, despite the decrease of rCBF, which suggests that rCBF was decreased to match the decrease of CMR rather than a decrease of cardiac output. Because increasing the dose of propranolol did not significantly affect the heterogeneity of SvO2, rCBF, or O2 consumption, our data suggest that there is a limitation in altering the CBF, metabolism, and the heterogeneity of SvO2, which are mediated through ß-adrenergic receptors.

There are other possible reasons for this heterogeneity. There could be a time delay of the metabolic supply behind the metabolic demand, variation of regional metabolism, different hematocrit, microregional variation of the ratio of O2 supply to consumption, rheologic factors, inhomogeneous anatomic distribution of vessels and neurons, or methodologic limitations that could affect the CV of the SvO2 by 3%–4% (18). It is not clear whether propranolol affects these other factors, which may, in turn, change the heterogeneity. It is likely that the spatial heterogeneity of SvO2 in the brain might originate from more than one contributing factor. Some factors may affect others or may be superimposed.

In conclusion, there is heterogeneity of the microregional O2 balance during isoflurane anesthesia. Propranolol was effective in decreasing the heterogeneity of microregional O2 balance and decreasing the number of veins with relatively low O2 saturation under isoflurane anesthesia.


   Acknowledgments
 
We thank Patricia A. Sheffield, MA, for her expert editorial assistance.


   Footnotes
 
Presented in part at the annual meeting of the American Society of Anesthesiologists, Orlando, FL, October, 1998.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Friedland RP, Iadecola C. Roy and Sherrington (1890) a centennial reexamination of "on the regulation of the blood-supply of the brain." Neurology 1991;41:10–4.[Free Full Text]
  2. Sinha AK, Chi OZ, Weiss HR. Effect of pentobarbital on cerebral regional venous O2 saturation heterogeneity. Brain Res 1992;591:146–50.[Web of Science][Medline]
  3. Chi OZ, Wei HM, O'Hara D, et al. Effects of pentobarbital and isoflurane on regional cerebral oxygen extraction and consumption with middle cerebral artery occlusion in rats. Anesthesiology 1993;79:299–305.[Web of Science][Medline]
  4. Chi OZ, Wei HM, Klein SL, Weiss HR. Effect of ketamine on heterogeneity of cerebral microregional venous O2 saturation in the rat. Anesth Analg 1994;79:860–6.[Abstract/Free Full Text]
  5. Fennema M, Wessel JN, Faithfull NS, Erdmann W. Tissue oxygen tension in the cerebral cortex of the rabbit. Biol 1989;248:451–60.
  6. Kozniewska E, Weller L, Hoper J, et al. Cerebrocortical microcirculation in different stages of hypoxic hypoxia. Blood Flow Metab 1987;7:464–70.
  7. Wei HM, Chen WY, Sinha AK, Weiss HR. Effect of cervical sympathectomy and hypoxia on the heterogeneity of O2 saturation of small cerebrocortical veins. Cereb Blood Flow Metab 1993;13:269–75.[Web of Science][Medline]
  8. Buchweitz-Milton E, Weiss HR. Effect of salbutamol on regional cerebral oxygen consumption, flow and capillary and arteriolar perfusion. Neurol Res 1990;12:169–75.[Medline]
  9. Sercombe R, Aubineau P, Edvinsson L, et al. Pharmacological evidence in vitro and in vivo for functional beta 1 receptors in the cerebral circulation. Pfluegers Arch 1977;368:241–4.[Web of Science][Medline]
  10. MacKenzie ET, McCulloch J, O'Keane M, et al. Cerebral circulation and norepinephrine relevance of the blood-brain barrier. Am J Physiol 1976;231:483–8.[Abstract/Free Full Text]
  11. MacKenzie ET, McCulloch J, Harper AM. Influence of endogenous norepinephrine on cerebral blood flow and metabolism. Am J Physiol 1976;231:489–94.[Abstract/Free Full Text]
  12. Lawson NW, Meyer DJ Jr. Autonomic nervous system: physiology and pharmacology. In: Barash PG, Cullen BF, Stoelting RK, eds. Clinical anesthesia. Philadelphia:Lippincott-Raven, 1997:243–309.
  13. Aqyagi M, Deshmukh VD, Meyer JS, et al. Effect of beta-adrenergic blockade with propranolol on cerebral blood flow, autoregulation and CO2 responsiveness. Stroke 1976;7:291–5.[Abstract/Free Full Text]
  14. Hemmingsen R, Hertz MM, Barry DI. The effect of propranolol on cerebral oxygen consumption and blood flow in the rat measurements during normocapnia and hypercapnia. Acta Physiol Scan 1979;105:274–81.[Web of Science][Medline]
  15. Lasbennes F, Seylaz J. Local cerebral blood flow in gently restrained rats effects of propranolol and diazepam. Exp Brain Res 1986;63:169–72.[Web of Science][Medline]
  16. Westerlind A, Larsson LE, Haggendal J, Ekstrom-Jodal B. Effects of propranolol pretreatment on cerebral blood flow, oxygen uptake and catecholamine during metabolic acidosis following E. coli endotoxin in dogs. Acta Anaesthesiol Scand 1995;39:467–71.[Web of Science][Medline]
  17. Sakurada O, Kennedy C, Jehle J, et al. Measurement of local cerebral blood flow with [14C]-iodoantipyrine. Am J Physiol 1978;234:H59–66.[Abstract/Free Full Text]
  18. Buchweitz-Milton E, Weiss HR. Effect of middle cerebral artery occlusion on brain O2 supply and consumption determined microspectrophotometrically. Physiol 1987;253:H454–60.
  19. Edvinsson L. Neurogenic mechanisms in the cerebrovascular bed autonomic nerves, amine receptors and their effects on cerebral blood flow. Acta Physiol Scand 1975;427 (Suppl):1–35.
  20. Marin J, Rivilla F. Nerve endings and pharmacological receptors in cerebral vessels. Gen Pharmacol 1982;13:361–8.[Web of Science][Medline]
  21. O'Neill C, Fowler CJ, Marcusson JO, Winblad D. Adrenergic serotoninergic, histaminergic, and imipramine binding sites in post-mortal human cerebral microvessel preparations. Neural Transm 1988;73:177–89.
  22. Yokote H, Itakura T, Nakai K, et al. A role of the central catecholamine neurons in cerebral circulation. J Neurosurg 1986;65:370–5.[Web of Science][Medline]
  23. Sarelius IH, Duling BR. Direct measurement of microvessel hematocrit, red cell flux, velocity, and transit time. Am J Physiol 1982;243:H1018–26.[Abstract/Free Full Text]
  24. Saeki Y, Sato A, Sato Y, Trzebski A. Effects of stimulation of cervical sympathetic trunks with various frequencies on the local cortical cerebral blood flow measured by laser Doppler flowmetry in the rat. Jpn J Physiol 1990;40:15–32.[Web of Science][Medline]
  25. Astrup J, Sorensen PM, Sorensen HR. Inhibition of cerebral oxygen and glucose consumption in the dog by hypothermia, pentobarbital, and lidocaine. Anesthesiology 1981;55:263–8.[Web of Science][Medline]
Accepted for publication April 30, 1999.




This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
J. W. Johansen
Esmolol Promotes Electroencephalographic Burst Suppression During Propofol/Alfentanil Anesthesia
Anesth. Analg., December 1, 2001; 93(6): 1526 - 1531.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chi, O. Z.
Right arrow Articles by Weiss, H. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chi, O. Z.
Right arrow Articles by Weiss, H. R.

Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 1999 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press