scholarly journals Acute Intravenous Low- and High-Dose Cocaine Reduces Quantitative Global and Regional Cerebral Blood Flow in Recently Abstinent Subjects with Cocaine use Disorder

2005 ◽  
Vol 25 (7) ◽  
pp. 928-936 ◽  
Author(s):  
Bankole A Johnson ◽  
Michael A Dawes ◽  
John D Roache ◽  
Lynda T Wells ◽  
Nassima Ait-Daoud ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Time Course ◽  
Low Dose ◽  
Statistical Significance ◽  
Cerebral Hypoperfusion ◽  
High Dose ◽  
Double Blind ◽  
Cocaine Use

Cocaine-induced hypoperfusion, a risk factor for ischemic stroke, has not been fully characterized during experimental drug-taking among individuals with cocaine use disorder. We sought to examine cocaine's dose-dependent, time-related effects on cerebral blood flow. In a double-blind, randomized human laboratory study with a counterbalanced order of drug administration, 31 male and female subjects with cocaine use disorder were divided into two groups receiving either (a) low-dose cocaine (0.325 mg/kg intravenously) or placebo ( N = 15) or (b) high-dose cocaine (0.650 mg/kg intravenously) or placebo ( N = 16). The different dose conditions were administered on test days separated by a rest period of ≥48 h. Cerebral blood flow was assessed quantitatively using H2O15 positron emission tomography. Experimentally administered low- and high-dose cocaine conditions versus their corresponding placebo conditions were associated with global and regional hypoperfusion. The trend for high- versus low-dose cocaine to be associated with greater hypoperfusion achieved statistical significance only for the dopamine-rich sublobar and midbrain regions. Cocaine's hypoperfusion effects were maximal at 8 mins after infusion (i.e., at about the expected peak of intravenous cocaine levels) and had mostly dissipated by 32 mins after infusion. Although hypoperfusion occurred throughout the brain, the left hemispheric dopamine-rich sublobar region was the most severely affected. Cocaine-induced cerebral hypoperfusion is associated with the time course of its pharmacological effects, and dopamine-rich areas, particularly in the left hemisphere, may be most vulnerable. Increasingly larger doses of cocaine may be associated with greater risk for ischemic stroke.

Hemodynamic effects of recombinant human erythropoietin on the central nervous system after subarachnoid hemorrhage: reduction of microcirculatory impairment and functional deficits in a rabbit model

2008 ◽  
Vol 109 (6) ◽  
pp. 1155-1164 ◽  
Author(s):  
Amanda M. Murphy ◽  
Anargyros Xenocostas ◽  
Pria Pakkiri ◽  
Ting-Yim Lee
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Recombinant Human Erythropoietin ◽  
Low Dose ◽  
Saline Group ◽  
High Dose ◽  
Hemodynamic Effects ◽  
Neurological Outcomes ◽  
Human Erythropoietin

Object The authors investigated the hemodynamic effects of recombinant human erythropoietin (rhEPO) after subarachnoid hemorrhage (SAH) in rabbits. Methods The authors used male New Zealand White rabbits in this study divided into the following groups: SAH plus saline (16 rabbits), SAH plus low-dose rhEPO (16 rabbits; 1500 IU/kg on Day 0 and 500 IU/kg on Days 2 and 4), SAH plus high-dose rhEPO (10 rabbits; 1500 IU/kg on Days 0, 2, 4, and 6), and sham (6 rabbits). Computed tomography perfusion studies and CT angiography were performed for 1 hour after SAH on Day 0, and once each on Days 2, 4, 7, 9, and 16 after SAH. Assessments of neurological function and tissue histology were also performed. Results The mortality rate was significantly lower after rhEPO treatment (12%) than after saline treatment (44%) (p < 0.05). Neurological outcomes in the low-dose and high-dose rhEPO groups were better than in the saline group after SAH (p < 0.05), and the cerebral blood flow in the high-dose rhEPO group was greater than that in the saline group (p < 0.05). The mean transit time was significantly lower on Days 2 and 4 in the low-dose and high-dose rhEPO groups than in the saline group, but increased significantly on Day 7 in both groups (p < 0.05). The hematocrit increased significantly from baseline values in the high-dose and low-dose rhEPO groups on Days 4 and 7, respectively (p < 0.05). Conclusions Treatment with rhEPO after experimental SAH is associated with improved cerebral blood flow and microcirculatory flow as reflected by lower mean transit times. Improved tissue perfusion correlated with reduced mortality and improved neurological outcomes. Further investigation of the impact of increasing hematocrit on hemodynamic changes is needed.

scholarly journals A Novel Method to Derive Separate Gray and White Matter Cerebral Blood Flow Measures from MR Imaging of Acute Ischemic Stroke Patients

2005 ◽  
Vol 25 (9) ◽  
pp. 1236-1243 ◽  
Author(s):  
Jessica E Simon ◽  
Michael S Bristow ◽  
Hong Lu ◽  
M Louis Lauzon ◽  
Robert A Brown ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Spin Echo ◽  
Statistical Significance ◽  
Mean Transit Time ◽  
Inversion Recovery ◽  
Normal Brain

Perfusion-weighted imaging (PWI) measures can predict tissue outcome in acute ischemic stroke. Accuracy might be improved if differential tissue susceptibility to ischemia is considered. We present a novel voxel-by-voxel analysis to characterize cerebral blood flow (CBF) separately in gray (GM) and white matter (WM). Ten patients were scanned with inversion-recovery spin-echo EPI (IRSEPI), diffusion-weighted imaging (DWI), PWI<6 h from onset and fluid attenuated inversion-recovery (FLAIR) at 30 days. Image processing included coregistration to PWI, automatic segmentation of IRSEPI into GM, WM and CSF and semiautomatic segmentation of DWI/FLAIR to derive the acute and 30-day lesions. Five tissue compartments were defined: (1) ‘Core’ (abnormal acutely and at 30 days), (2) ‘Growth’ (or ‘infarcted penumbra', abnormal only at 30 days), (3) ‘Reversed’ (abnormal acutely but normal at 30 days), (4) ‘MTT-Delayed ‘ (tissue with delayed mean transit time but not part of the acute or 30-day lesion), and (5) ‘Normal’ brain. Cerebral blood flow in GM and WM of each compartment was obtained from quantitative maps. Gray matter and WM mean CBF in the growth region differed by 5.5 mL/100 g min ( P = 0.015). Mean CBF also differed significantly within normal and MTT-Delayed compartments. The difference in the reversed region approached statistical significance. In core, GM and WM CBF did not differ. The results suggest separate ischemic thresholds for GM and WM in stroke penumbra.

Cerebral blood flow responsivity to CO2 in anesthetized chronically diabetic dogs

1993 ◽  
Vol 264 (4) ◽  
pp. H1069-H1075 ◽  
Author(s):  
F. E. Sieber ◽  
P. R. Brown ◽  
Y. Wu ◽  
R. C. Koehler ◽  
R. J. Traystman
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Glucose ◽  
Low Dose ◽  
Insulin Treatment ◽  
High Dose ◽  
Acute Hyperglycemia ◽  
Glucose Levels ◽  
Cerebrovascular Resistance ◽  
Diabetic Dogs

The effect of diabetes mellitus on the cerebrovascular response to CO2 is unclear. We examined the effects of diabetes on cerebral blood flow (CBF) and cerebral oxygen uptake (CMRO2) during CO2 alterations. Four groups of dogs were studied: nondiabetic, normoglycemic controls; non-diabetic acute hyperglycemia; diabetic (pancreatectomy) with high-dose insulin treatment to maintain blood glucose between 4.0 and 6.0 mM; and diabetic with low-dose insulin treatment to maintain blood glucose at 13.2 +/- 0.4 mM. Six weeks after either sham surgery or pancreatectomy, dogs were anesthetized with fentanyl (50 micrograms/kg) plus pentobarbital (10 mg/kg), and microsphere determinations of CBF were made during normo-, hypo-, and hypercapnia. On the day of the study, arterial glucose levels in the control, acute hyperglycemia, and high- and low-dose insulin diabetic groups were 4.0 +/- 0.3, 14.9 +/- 2.5, 3.3 +/- 0.8, and 13.3 +/- 0.7 mM, respectively, at control. The corresponding baseline CMRO2 levels were 2.8 +/- 0.2, 3.0 +/- 0.2, 4.1 +/- 0.4, and 4.0 +/- 0.3 ml O2.100 g-1 x min,1, and the values in both diabetic groups were higher than control. Normocapnic CBF in the acute hyperglycemia, high-dose insulin, and low-dose insulin groups was elevated from control (54 +/- 3, 50 +/- 3, 51 +/- 3 vs. 36 +/- 1 ml x 100 g-1 x min-1) and cerebrovascular resistance was lower (2.24 +/- 0.15, 2.51 +/- 0.14, 2.38 +/- 0.21 vs. 3.35 +/- 0.18 mmHg.ml-1 x 100 g.min). CBF responses to both hypercapnia and hypocapnia were similar among groups. Thus both acute hyperglycemia and diabetes decrease cerebrovascular resistance and increase CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract WP96: The Efficacy and Safety of HT047 in Patients With Acute Ischemic Stroke: A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase II Trial

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Sung Hyuk Heo ◽  
Bum Joon Kim ◽  
Dae-Il Chang ◽  
Hye-Yeon Choi ◽  
Young Seo Kim ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Low Dose ◽  
Phase Ii Trial ◽  
Study Groups ◽  
High Dose ◽  
Motor Score ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Parallel Group

Introduction: HT047 is an herbal mixture extract of the Scutellaria baicalensis and Pueraria lobata plants, which have been widely used to treat ischemic stroke in traditional Korean medicine. The aims of this trial are to investigate whether HT047 can improve neurological status, particularly motor function, in acute ischemic stroke patients, and to determine the safety and tolerance of HT047. Methods: In this randomized, double-blind, placebo-controlled, parallel-group, phase II trial, we enrolled patients with acute ischemic stroke within the past 14 days from 8 centers in Korea. The participating patients must have a Fugl-Meyer Assessment (FMA) motor score ≤55 with arm or leg weakness, and Korean version of the National Institutes of Health Stroke Scale (K-NIHSS) score of ≥4 and ≤15. Seventy-eight participants will be randomized in a 1:1:1 ratio and given high-dose HT047 (750 mg three times a day), low-dose HT047 (500 mg three times a day), or a placebo for 12 weeks. The primary endpoint is the change in FMA motor score between baseline and week 12. The trial is registered with ClinicalTrials.gov, NCT02828540. Results: Between Aug, 2016, and Aug, 2018, we randomly assigned 78 patients to one of the three study groups, of whom 66 patients were assessed for the primary endpoint in full analysis set. The median (min, max) changes in FMA motor score of high-dose HT047 and low-dose HT047 were 24 (0, 63) and 43 (-2, 70) (placebo group=28 [0, 63], p=0.929 and p=0.705, respectively). The prevalence of favorable outcome defined as modified Rankin scale score of 0-2 were 47.6% (p=0.919) in high-dose HT047 group and 57.1% (p=0.106) in low-dose HT047 group (31.6% in placebo group). Adverse events were similar across the three study groups. Conclusions: This study is a first-in-human trial of HT047, and there were no between-group differences on the primary and secondary endpoints.

Effects of aging on cerebral vascular responses to serotonin in rats

1993 ◽  
Vol 264 (6) ◽  
pp. H2136-H2140 ◽  
Author(s):  
M. A. Hajdu ◽  
R. T. McElmurry ◽  
D. D. Heistad ◽  
G. L. Baumbach
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Low Dose ◽  
Cerebral Arteries ◽  
High Dose ◽  
Aged Rats ◽  
Adult Rats ◽  
Effects Of Aging

The purpose of this study was to examine effects of aging on responses of large cerebral arteries to serotonin. We measured cerebral microvascular pressure (with a micropipette and servo-null method), diameter of pial arterioles, and cerebral blood flow (microspheres) in adult (12- to 14-mo-old, n = 15) and aged (24- to 27-mo-old, n = 14) Wistar rats. Responses to intra-atrial infusion of serotonin (5 and 50 micrograms.kg-1.min-1) were examined. Infusion of the low dose of serotonin decreased mean arterial pressure and pial arteriolar pressure in adult and aged rats to similar levels. Cerebral blood flow was not reduced in adult or aged rats during infusion of the low dose of serotonin. The high dose of serotonin did not affect mean arterial pressure but reduced pial arteriolar pressure [from 46 +/- 4 to 23 +/- 2 (SE) in adult rats and from 52 +/- 3 to 18 +/- 4 mmHg in aged rats]. The high dose of serotonin increased large-artery resistance from 0.9 +/- 0.1 to 1.6 +/- 0.2 in adult rats and from 0.9 +/- 0.1 to 2.7 +/- 0.6 mmHg.ml-1.min.100 g in aged rats. Cerebral blood flow was reduced significantly in aged rats (from 59 +/- 3 to 41 +/- 6 ml.min-1.100 g-1), but not in adult rats, during infusion of the high dose of serotonin. We conclude that aging augments constrictor responses of large cerebral arteries to intravascular serotonin, which results in a reduction of cerebral blood flow in aged but not adult rats.

scholarly journals No evidence for direct effects of recombinant human erythropoietin on cerebral blood flow and metabolism in healthy humans

2018 ◽  
Vol 124 (4) ◽  
pp. 1107-1116 ◽  
Author(s):  
Mark Bitsch Vestergaard ◽  
Otto Mølby Henriksen ◽  
Ulrich Lindberg ◽  
Niels Jacob Aachmann-Andersen ◽  
Kristian Lisbjerg ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Direct Effect ◽  
Low Dose ◽  
Metabolic Response ◽  
Cerebral Metabolism ◽  
Lactate Concentration ◽  
High Dose ◽  
Healthy Humans ◽  
Positron Emission

Erythropoietin (EPO) is expressed in human brain tissue, but its exact role is unknown. EPO may improve the efficiency of oxidative metabolism and has neuroprotective properties against hypoxic injuries in animal models. We aimed to investigate the effect of recombinant human EPO (rHuEPO) administration on healthy cerebral metabolism in humans during normoxia and during metabolic stress by inhalation of 10% O2hypoxic air. Twenty-four healthy men participated in a two-arm double-blind placebo-controlled trial. rHuEPO was administered as a low dose (5,000 IU) over 4 wk ( n = 12) or as a high dose (500 IU·kg body wt−1·day−1) for three consecutive days ( n = 12). Global cerebral blood flow (CBF) and metabolic rate of glucose (CMRglc) were measured with positron emission tomography. CBF, metabolic rate of oxygen ([Formula: see text]), and cerebral lactate concentration were measured by magnetic resonance imaging and spectroscopy. Low-dose treatment increased hemoglobin and was associated with a near-significant decrease in CBF during baseline normoxia. High-dose treatment caused no change in CBF. Neither treatment had an effect on normoxia CMRglc, [Formula: see text], or lactate concentration or an effect on the cerebral metabolic response to inhalation of hypoxic air. In conclusion, the study found no evidence for a direct effect of rHuEPO on cerebral metabolism.NEW & NOTEWORTHY We demonstrate with magnetic resonance imaging and positron emission tomography that administration of erythropoietin does not have a substantial direct effect on healthy human resting cerebral blood flow or effect on cerebral glucose and oxygen metabolism. Also, administration of erythropoietin did not have a direct effect on the metabolic response to acute hypoxic stress in healthy humans, and a suggested neuroprotective effect from erythropoietin is therefore likely not a direct effect of erythropoietin on cerebral metabolism.

Effects of indomethacin on brain blood flow, cerebral metabolism, and sagittal sinus prostanoids after hypoxia

1995 ◽  
Vol 269 (4) ◽  
pp. H1450-H1459 ◽  
Author(s):  
M. G. Coyle ◽  
W. Oh ◽  
K. H. Petersson ◽  
B. S. Stonestreet
Keyword(s):  
Blood Flow ◽  
Low Dose ◽  
Cerebral Metabolism ◽  
Brain Regions ◽  
Cerebral Hypoperfusion ◽  
High Dose ◽  
Brain Blood Flow ◽  
Newborn Piglets ◽  
Sagittal Sinus ◽  
Dose Dependent

We tested the hypotheses that during recovery from hypoxia, newborn piglets exhibit a posthypoxic cerebral hyperemia, indomethacin-pretreated piglets exhibit a posthypoxic cerebral hypoperfusion, and that the changes caused by indomethacin are dose dependent and related to the loss of prostanoids. We studied piglets exposed to 40 min of hypoxia after pretreatment with high (5 mg/kg, n = 9) or low (0.3 mg/kg, n = 8) doses of indomethacin or placebo (n = 9) and allowed to recover for 120 min. In the placebo and low-dose pretreatment groups, total and regional brain blood flow increased during hypoxia but returned to baseline 10 min after hypoxia. High-dose indomethacin pretreatment was associated with a posthypoxic hypoperfusion to certain brain regions at 10 min of recovery to values similar to those after indomethacin treatment before the onset of hypoxia. During and after hypoxia, the cerebral metabolic rate of oxygen was preserved in both the placebo and low-dose groups and decreased significantly during hypoxia in the high-dose group. Sagittal sinus prostacyclin was reduced significantly in both indomethacin-treated groups throughout the study. We conclude that a posthypoxic hyperemia is not observed in newborn piglets. This finding was not altered by pretreatment with a therapeutic dose of indomethacin, whereas a pharmacological dose was associated with selective hypoperfusion to certain brain regions both before hypoxia and during recovery from hypoxia.

Patterns of Cerebral Blood Flow and Systemic Hemodynamics During Arithmetic Processing

2008 ◽  
Vol 22 (2) ◽  
pp. 81-90 ◽  
Author(s):  
Natalie Werner ◽  
Neval Kapan ◽  
Gustavo A. Reyes del Paso
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Time Course ◽  
Doppler Sonography ◽  
Transcranial Doppler Sonography ◽  
Systemic Hemodynamics ◽  
Heart Period ◽  
Blood Flow Velocities ◽  
Flow Velocities

The present study explored modulations in cerebral blood flow and systemic hemodynamics during the execution of a mental calculation task in 41 healthy subjects. Time course and lateralization of blood flow velocities in the medial cerebral arteries of both hemispheres were assessed using functional transcranial Doppler sonography. Indices of systemic hemodynamics were obtained using continuous blood pressure recordings. Doppler sonography revealed a biphasic left dominant rise in cerebral blood flow velocities during task execution. Systemic blood pressure increased, whereas heart period, heart period variability, and baroreflex sensitivity declined. Blood pressure and heart period proved predictive of the magnitude of the cerebral blood flow response, particularly of its initial component. Various physiological mechanisms may be assumed to be involved in cardiovascular adjustment to cognitive demands. While specific contributions of the sympathetic and parasympathetic systems may account for the observed pattern of systemic hemodynamics, flow metabolism coupling, fast neurogenic vasodilation, and cerebral autoregulation may be involved in mediating cerebral blood flow modulations. Furthermore, during conditions of high cardiovascular reactivity, systemic hemodynamic changes exert a marked influence on cerebral blood perfusion.

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