Unaltered cerebral blood flow during hypoglycemic activation of the sympathochromaffin system in humans

1993 ◽  
Vol 265 (4) ◽  
pp. R883-R887 ◽  
Author(s):  
W. J. Powers ◽  
P. J. Boyle ◽  
I. B. Hirsch ◽  
P. E. Cryer
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Plasma Glucose ◽  
Plasma Norepinephrine ◽  
Plasma Catecholamine ◽  
Primary Role ◽  
Plasma Epinephrine ◽  
Glucose Levels ◽  
Positron Emission ◽  
Arterial Plasma

To determine if increases in plasma epinephrine and norepinephrine caused by hypoglycemia are associated with increments in cerebral blood flow (CBF), we measured CBF with positron emission tomography in normal humans at ambient fasting arterial plasma glucose levels and at clamped plasma glucose levels of 5.3, 3.5, and 2.8 mmol/l using the hyperinsulinemic, stepped hypoglycemic clamp technique. Despite significant increases in plasma epinephrine to 7,340 +/- 350 (SE) pmol/l and in plasma norepinephrine to 3.32 +/- 0.35 nmol/l, mean hemispheric CBF (41 +/- 1, 49 +/- 1, 48 +/- 2, and 51 +/- 3 ml x 100 g-1 x min-1) remained constant at the ambient (5.2), 5.3, 3.5, and 2.8 mmol/l glycemic levels, respectively. Furthermore, there was no correlation between CBF and either plasma epinephrine levels ranging from 160 to 10,580 pmol/l or plasma norepinephrine levels ranging from 0.56 to 5.10 nmol/l. Failure to demonstrate any dose-response relationship between plasma catecholamine levels and CBF argues against their primary role in cerebrovascular control during hypoglycemia.

scholarly journals Examination of Potential Mechanisms in the Enhancement of Cerebral Blood Flow by Hypoglycemia and Pharmacological Doses of Deoxyglucose

1997 ◽  
Vol 17 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Naoaki Horinaka ◽  
Nicole Artz ◽  
Jane Jehle ◽  
Shinichi Takahashi ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Lactate ◽  
Insulin Hypoglycemia ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Arterial Plasma

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 m M, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3– concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 m M) or pharmacological doses of deoxyglucose.

Increased Cerebral Blood Flow and Plasma Epinephrine in Hypoglycemic, Preterm Neonates

PEDIATRICS ◽  
1990 ◽  
Vol 85 (2) ◽  
pp. 172-176 ◽  
Author(s):  
O. Pryds ◽  
N. J. Christensen ◽  
B. Friis-Hansen
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Glucose ◽  
Preterm Neonates ◽  
Plasma Norepinephrine ◽  
Plasma Epinephrine ◽  
Intravenous Glucose ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Blood Glucose Levels

Cerebral blood flow, plasma epinephrine, and plasma norepinephrine were measured in 25 spontaneously breathing, preterm neonates (mean gestational age 30.4 weeks) 2 hours after birth, during a routine screening for low blood glucose levels. Increased cerebral blood flow and plasma epinephrine values were observed when blood glucose levels were low, whereas plasma norepinephrine was constant throughout the blood glucose range. Hypoglycemia (defined as blood glucose concentration <30 mg/dL) was found in 13 neonates who were treated with intravenous glucose and milk enterally. Blood glucose levels were normal in the remaining 12 control neonates who received milk by a gastric line. Approximately 30 minutes after treatment with intravenous glucose and/or milk, cerebral blood flow had decreased by a mean of 11.3% in the 13 hypoglycemic neonates but was still 37.5% higher than cerebral blood flow in the control neonates despite normalization of plasma epinephrine concentration. Mean arterial blood pressure and blood gas values were identical between groups throughout the investigation. It is suggested that a normal coupling between cerebral metabolic demands and flow is present in very preterm neonates and that epinephrine may play a role in the cerebral hyperperfusion. Although none of the neonates had clinical signs of hypoglycemia, the data suggest that counterregulatory mechanisms are invoked when blood glucose values are <30 to 45 mg/dL.

Effects of elevated plasma epinephrine on glucose utilization and blood flow in conscious rat brain

1997 ◽  
Vol 272 (4) ◽  
pp. H1666-H1671
Author(s):  
N. Horinaka ◽  
N. Artz ◽  
M. Cook ◽  
C. Holmes ◽  
D. S. Goldstein ◽  
...  
Keyword(s):  
Blood Flow ◽  
Glucose Utilization ◽  
Brain Structures ◽  
Plasma Epinephrine ◽  
Conscious Rat ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Arterial Plasma ◽  
Student’S T ◽  
Normal Controls

Acute glucoprivation increases cerebral blood flow (CBF), which is often attributed to the associated rise in plasma epinephrine levels. This study examined directly the effects of comparable increases in plasma epinephrine levels achieved by continuous intravenous infusions of epinephrine in normoglycemic, unanesthetized rats on local and overall CBF and cerebral glucose utilization (1CMRglc). CBF was determined by the autoradiographic [14C]iodoantipyrine method in six unanesthetized rats in which epinephrine dissolved in 1% ascorbic acid-1 mM EDTA was infused at a rate of 1 microg/min and in five normal controls infused with the vehicle alone. 1CMRglc was determined by the autoradiographic [14C]deoxyglucose method in six conscious rats infused similarly with the epinephrine solution and in six normal controls treated with the vehicle alone. The epinephrine infusions raised arterial plasma epinephrine levels 10- to 20-fold and increased arterial blood pressure and plasma glucose levels. Local CBF, however, was significantly changed (P < 0.05, Student's t-test) in only 2 of 25 structures examined, and the changes were decreases not increases. 1CMRglc was not changed significantly in any of 42 brain structures examined, and average blood flow and glucose utilization in the brain as a whole were unaffected. These results show that high circulating levels of epinephrine similar to those accompanying glucoprivation alter neither local nor overall CBF and glucose utilization and cannot explain the increases in CBF associated with glucoprivation.

Reversal of Focal Misery Perfusion after Intracranial Angioplasty: Case Report

Neurosurgery ◽  
2001 ◽  
Vol 48 (2) ◽  
pp. 436-440 ◽  
Author(s):  
Colin P. Derdeyn ◽  
DeWitte T. Cross ◽  
Christopher J. Moran ◽  
Ralph G. Dacey
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Carotid Artery ◽  
Intracranial Stenosis ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Positron Emission ◽  
Misery Perfusion ◽  
Before And After ◽  
Hemodynamic Measurements

Abstract OBJECTIVE AND IMPORTANCE The presence of reduced blood flow and increased oxygen extraction fraction (OEF) (misery perfusion) in the hemisphere distal to an occluded carotid artery is a proven risk factor for subsequent stroke. Whether angioplasty of intracranial stenosis is sufficient to reverse this condition has not been documented. CLINICAL PRESENTATION A 67-year-old man exhibited progressive right hemispheric ischemic symptoms despite maximal antiplatelet and antithrombotic therapy. Angiography demonstrated focal 80% stenosis of the supraclinoid segment of the ipsilateral internal carotid artery. TECHNIQUE 15O positron emission tomographic measurements of cerebral blood flow and OEF were made before and after transfemoral percutaneous angioplasty. OEF values measured before angioplasty were elevated in the middle cerebral artery distal to the stenosis. Angioplasty reduced the degree of luminal stenosis to 40% (linear diameter). OEF values measured 36 hours after angioplasty were normal. CONCLUSION Angioplasty of intracranial stenosis can restore normal cerebral blood flow and oxygen extraction, despite mild residual stenosis after the procedure. Hemodynamic measurements may be useful for the identification of patients with the greatest potential to benefit from angioplasty.

scholarly journals Autoregulation of Cerebral Blood Flow to Changes in Arterial Pressure in Mild Alzheimer's Disease

2010 ◽  
Vol 30 (11) ◽  
pp. 1883-1889 ◽  
Author(s):  
Allyson R Zazulia ◽  
Tom O Videen ◽  
John C Morris ◽  
William J Powers
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Arterial Pressure ◽  
The Elderly ◽  
Local Defect ◽  
Clinical Dementia Rating ◽  
Positron Emission ◽  
Before And After

Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer's disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75±6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.5 or 1.0) underwent 15O-positron emission tomography (PET) CBF measurements before and after mean arterial pressure (MAP) was lowered from 107±13 to 92±9 mm Hg with intravenous nicardipine; 11C-PIB-PET imaging and magnetic resonance imaging (MRI) were also obtained. There were no significant differences in mean CBF before and after MAP reduction in the bilateral hemispheres (−0.9±5.2 mL per 100 g per minute, P=0.4, 95% confidence interval (CI)=−3.4 to 1.5), cortical borderzones (−1.9±5.0 mL per 100 g per minute, P=0.10, 95% CI=−4.3 to 0.4), regions of T2W-MRI-defined leukoaraiosis (−0.3±4.4 mL per 100 g per minute, P=0.85, 95% CI=−3.3 to 3.9), or regions of peak 11C-PIB uptake (−2.5±7.7 mL per 100 g per minute, P=0.30, 95% CI=−7.7 to 2.7). The absence of significant change in CBF with a 10 to 15 mm Hg reduction in MAP within the normal autoregulatory range demonstrates that there is neither a generalized nor local defect of autoregulation in AD.

scholarly journals Effects of Acetazolamide on Cerebral Blood Flow, Blood Volume, and Oxygen Metabolism: A Positron Emission Tomography Study with Healthy Volunteers

2001 ◽  
Vol 21 (12) ◽  
pp. 1472-1479 ◽  
Author(s):  
Hidehiko Okazawa ◽  
Hiroshi Yamauchi ◽  
Kanji Sugimoto ◽  
Hiroshi Toyoda ◽  
Yoshihiko Kishibe ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Metabolic Rate ◽  
Blood Volume ◽  
Cerebral Blood Volume ◽  
Capillary Blood ◽  
Emission Tomography ◽  
Positron Emission ◽  
Capillary Blood Volume

To evaluate changes in cerebral hemodynamics and metabolism induced by acetazolamide in healthy subjects, positron emission tomography studies for measurement of cerebral perfusion and oxygen consumption were performed. Sixteen healthy volunteers underwent positron emission tomography studies with15O-gas and water before and after intravenous administration of acetazolamide. Dynamic positron emission tomography data were acquired after bolus injection of H215O and bolus inhalation of15O2. Cerebral blood flow, metabolic rate of oxygen, and arterial-to-capillary blood volume images were calculated using the three-weighted integral method. The images of cerebral blood volume were calculated using the bolus inhalation technique of C15O. The scans for cerebral blood flow and volume and metabolic rate of oxygen after acetazolamide challenge were performed at 10, 20, and 30 minutes after drug injection. The parametric images obtained under the two conditions at baseline and after acetazolamide administration were compared. The global and regional values for cerebral blood flow and volume and arterial-to-capillary blood volume increased significantly after acetazolamide administration compared with the baseline condition, whereas no difference in metabolic rate of oxygen was observed. Acetazolamide-induced increases in both blood flow and volume in the normal brain occurred as a vasodilatory reaction of functioning vessels. The increase in arterial-to-capillary blood volume made the major contribution to the cerebral blood volume increase, indicating that the raise in cerebral blood flow during the acetazolamide challenge is closely related to arterial-to-capillary vasomotor responsiveness.

scholarly journals Blockade of Cerebral Blood Flow Response to Insulin-Induced Hypoglycemia by Caffeine and Glibenclamide in Conscious Rats

1997 ◽  
Vol 17 (12) ◽  
pp. 1309-1318 ◽  
Author(s):  
Naoaki Horinaka ◽  
Tang-Yong Kuang ◽  
Hazel Pak ◽  
Robert Wang ◽  
Jane Jehle ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Degradation Products ◽  
Dependent Manner ◽  
Conscious Rats ◽  
Intravenous Injections ◽  
Adenosine Receptor Antagonist ◽  
Flow Response ◽  
Arterial Plasma ◽  
Dose Dependent

The possibility that adenosine and ATP-sensitive potassium channels (KATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a KATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats ( P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia ( P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and KATP channels may play a role in the increases in CBF during hypoglycemia.

Neural Mechanism of Propofol Anesthesia in Severe Depression

2003 ◽  
Vol 98 (5) ◽  
pp. 1101-1111 ◽  
Author(s):  
Kenichi Ogawa ◽  
Takeshi Uema ◽  
Nobutaka Motohashi ◽  
Masami Nishikawa ◽  
Harumasa Takano ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Statistical Parametric Mapping ◽  
Severe Depression ◽  
Dose Effect ◽  
Emission Tomography ◽  
Association Cortex ◽  
Depressed Patients ◽  
Positron Emission

Background The precise neural mechanisms of propofol anesthesia in humans are still unknown. The authors examined the acute effects of propofol on regional cerebral blood flow (rCBF) using positron emission tomography in patients with severe depression. Methods In six severely depressed patients (mean age, 55.0 yr) scheduled for electroconvulsive therapy, anesthetic levels were monitored by electroencephalography, and rCBF was serially quantified in the awake, sedated, and anesthetized states. The authors used high-resolution positron emission tomography with 15O-labeled water and statistical parametric mapping 99 for imaging and analysis of the data. Results Global cerebral blood flow showed sharp decreases from the awake level during the administration of propofol, decreasing 26.8% in the sedated state and 54.4% in the anesthetized state. Moreover, a dose effect was seen in both parietal cortices and the left lateral prefrontal region with larger regions of relative decrease in rCBF at higher propofol doses. At the higher dose, the values of rCBF in the pulvinar nucleus of the thalamus, the pontine tegmentum, and the cerebellar cortex were also affected. Meanwhile, there were few changes of relative rCBF in the basal frontal lobes during both sedated and anesthetized states. Conclusions As in earlier studies using normal subjects, pronounced suppression in rCBF in the brain stem reticular formation, the thalamus, and the parietal association cortex occurred even in severely depressed patients. However, previously reported decreases in rCBF in the basal frontal lobe were absent in depressed patients.

scholarly journals Carbohydrate ingestion does not alter skeletal muscle AMPK signaling during exercise in humans

2006 ◽  
Vol 291 (3) ◽  
pp. E566-E573 ◽  
Author(s):  
Robert S. Lee-Young ◽  
Matthew J. Palmer ◽  
Kelly C. Linden ◽  
Kieran LePlastrier ◽  
Benedict J. Canny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Glucose ◽  
Plasma Epinephrine ◽  
Muscle Lactate ◽  
Carbohydrate Ingestion ◽  
Ampk Signaling ◽  
Glucose Levels ◽  
Exercise Induced ◽  
Exercise In Humans

There is evidence that increasing carbohydrate (CHO) availability during exercise by raising preexercise muscle glycogen levels attenuates the activation of AMPKα2 during exercise in humans. Similarly, increasing glucose levels decreases AMPKα2 activity in rat skeletal muscle in vitro. We examined the effect of CHO ingestion on skeletal muscle AMPK signaling during exercise in nine active male subjects who completed two 120-min bouts of cycling exercise at 65 ± 1% V̇o2 peak. In a randomized, counterbalanced order, subjects ingested either an 8% CHO solution or a placebo solution during exercise. Compared with the placebo trial, CHO ingestion significantly ( P < 0.05) increased plasma glucose levels and tracer-determined glucose disappearance. Exercise-induced increases in muscle-calculated free AMP (17.7- vs. 11.8-fold), muscle lactate (3.3- vs. 1.8-fold), and plasma epinephrine were reduced by CHO ingestion. However, the exercise-induced increases in skeletal muscle AMPKα2 activity, AMPKα2 Thr172 phosphorylation and acetyl-CoA Ser222 phosphorylation, were essentially identical in the two trials. These findings indicate that AMPK activation in skeletal muscle during exercise in humans is not sensitive to changes in plasma glucose levels in the normal range. Furthermore, the rise in plasma epinephrine levels in response to exercise was greatly suppressed by CHO ingestion without altering AMPK signaling, raising the possibility that epinephrine does not directly control AMPK activity during muscle contraction under these conditions in vivo.

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