scholarly journals Desferroxamine infusion increases cerebral blood flow: a potential association with hypoxia-inducible factor-1

2009 ◽  
Vol 116 (10) ◽  
pp. 771-779 ◽  
Author(s):  
Farzaneh A. Sorond ◽  
Michele L. Shaffer ◽  
Andrew L. Kung ◽  
Lewis A. Lipsitz
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Lactate Dehydrogenase ◽  
Cerebral Perfusion ◽  
Hypoxia Inducible Factor ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Cerebrovascular Resistance ◽  
Hypoxia Inducible Factor 1

Finding an effective means to improve cerebral perfusion during hypoxic/ischaemic stress is essential for neuroprotection. Studies in animal models of stroke have shown that desferroxamine activates HIF-1 (hypoxia-inducible factor-1), reduces brain damage and promotes functional recovery. The present study was designed to investigate the effects of desferroxamine infusion on the cerebral circulation in humans. Fifteen volunteers were enrolled in a randomized double-blind placebo-controlled crossover study. We measured cerebral blood flow velocity by transcranial Doppler ultrasonography in the middle cerebral artery, arterial blood pressure, end-tidal CO2, as well as HIF-1 protein and serum lactate dehydrogenase concentrations in response to 8 h of desferroxamine compared with placebo infusion. Cerebrovascular resistance was calculated from the ratio of steady-state beat-to-beat values for blood pressure to blood flow velocity. We found that desferroxamine infusion was associated with a significant cerebral vasodilation. Moreover, decreased cerebrovascular resistance was temporally correlated with an increased HIF-1 protein concentration as well as HIF-1 transcriptional activation, as measured by serum lactate dehydrogenase concentration. The findings of the present study provide preliminary data suggesting that activators of HIF-1, such as desferroxamine, may protect neurons against ischaemic injury by dilating cerebral vessels and enhancing cerebral perfusion.

Melatonin improves cerebral circulation security margin in rats

1998 ◽  
Vol 275 (1) ◽  
pp. H139-H144 ◽  
Author(s):  
Olivier Régrigny ◽  
Philippe Delagrange ◽  
Elizabeth Scalbert ◽  
Jeffrey Atkinson ◽  
Isabelle Lartaud-Idjouadiene
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Arterial Blood Pressure ◽  
Lower Limit ◽  
Mean Arterial Blood Pressure ◽  
Pressure Level ◽  
Cerebrovascular Resistance ◽  
Arterial Blood ◽  
Cerebral Blood Flow Autoregulation

Because melatonin is a cerebral vasoconstrictor agent, we tested whether it could shift the lower limit of cerebral blood flow autoregulation to a lower pressure level, by improving the cerebrovascular dilatory reserve, and thus widen the security margin. Cerebral blood flow and cerebrovascular resistance were measured by hydrogen clearance in the frontal cortex of adult male Wistar rats. The cerebrovasodilatory reserve was evaluated from the increase in the cerebral blood flow under hypercapnia. The lower limit of cerebral blood flow autoregulation was evaluated from the fall in cerebral blood flow following hypotensive hemorrhage. Rats received melatonin infusions of 60, 600, or 60,000 ng ⋅ kg−1 ⋅ h−1, a vehicle infusion, or no infusion ( n= 9 rats per group). Melatonin induced concentration-dependent cerebral vasoconstriction (up to 25% of the value for cerebrovascular resistance of the vehicle group). The increase in vasoconstrictor tone was accompanied by an improvement in the vasodilatory response to hypercapnia (+50 to +100% vs. vehicle) and by a shift in the lower limit of cerebral blood flow autoregulation to a lower mean arterial blood pressure level (from 90 to 50 mmHg). Because melatonin had no effect on baseline mean arterial blood pressure, the decrease in the lower limit of cerebral blood flow autoregulation led to an improvement in the cerebrovascular security margin (from 17% in vehicle to 30, 55, and 55% in the low-, medium-, and high-dose melatonin groups, respectively). This improvement in the security margin suggests that melatonin could play an important role in the regulation of cerebral blood flow and may diminish the risk of hypoperfusion-induced cerebral ischemia.

Effect of reduced cerebral perfusion pressure on cerebral blood flow following inhibition of nitric oxide synthesis

1998 ◽  
Vol 89 (3) ◽  
pp. 448-453 ◽  
Author(s):  
Ingunn R. Rise ◽  
Ole J. Kirkeby
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Intracranial Pressure ◽  
Cerebral Perfusion ◽  
Perfusion Pressure ◽  
Nitric Oxide Synthesis ◽  
Content Type ◽  
Cerebrovascular Resistance ◽  
Fine Print

Object. The authors tested the hypothesis in a porcine model that inhibition of nitric oxide synthesis during reduced cerebral perfusion pressure (CPP) affected the relative cerebral blood flow (CBF) and the cerebrovascular resistance. Methods. The CPP was reduced by inducing high cerebrospinal fluid pressure and hemorrhagic hypotension. With continuous blood and intracranial pressure monitoring, relative CPP was estimated using the laser Doppler flowmetry technique in nine pigs that received 40 mg/kg nitro-l-arginine methyl ester (l-NAME) and in nine control animals. The l-NAME caused a decrease in relative CBF (p < 0.01) and increases in cerebrovascular resistance (p < 0.01), blood pressure (p < 0.05), and CPP (p < 0.001). During high intracranial pressure there were no significant differences between the treated animals and the controls. After hemorrhage, there was no significant difference between the groups initially, but 30 minutes later the cerebrovascular resistance was decreased in the control group and increased in the l-NAME group relative to baseline (p < 0.05). Combined hemorrhage and high intracranial pressure increased the difference between the two groups with regard to cerebrovascular resistance (p < 0.05). Conclusions. These results suggest that nitric oxide synthesis inhibition affects the autoregulatory response of the cerebral circulation after cardiovascular compensation has taken place. Nitric oxide synthesis inhibition enhanced the undesirable effects of high intracranial pressure during hypovolemia.

scholarly journals Influence of cerebrovascular resistance on the dynamic relationship between blood pressure and cerebral blood flow in humans

2014 ◽  
Vol 116 (12) ◽  
pp. 1614-1622 ◽  
Author(s):  
J. D. Smirl ◽  
Y. C. Tzeng ◽  
B. J. Monteleone ◽  
P. N. Ainslie
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Artery ◽  
Function Analysis ◽  
Flow Dynamics ◽  
Pressure Flow ◽  
Cerebrovascular Resistance ◽  
Dynamic Relationship ◽  
Transfer Function Analysis

We examined the hypothesis that changes in the cerebrovascular resistance index (CVRi), independent of blood pressure (BP), will influence the dynamic relationship between BP and cerebral blood flow in humans. We altered CVRi with (via controlled hyperventilation) and without [via indomethacin (INDO, 1.2 mg/kg)] changes in PaCO2. Sixteen subjects (12 men, 27 ± 7 yr) were tested on two occasions (INDO and hypocapnia) separated by >48 h. Each test incorporated seated rest (5 min), followed by squat-stand maneuvers to increase BP variability and improve assessment of the pressure-flow dynamics using linear transfer function analysis (TFA). Beat-to-beat BP, middle cerebral artery velocity (MCAv), posterior cerebral artery velocity (PCAv), and end-tidal Pco2 were monitored. Dynamic pressure-flow relations were quantified using TFA between BP and MCAv/PCAv in the very low and low frequencies through the driven squat-stand maneuvers at 0.05 and 0.10 Hz. MCAv and PCAv reductions by INDO and hypocapnia were well matched, and CVRi was comparably elevated ( P < 0.001). During the squat-stand maneuvers (0.05 and 0.10 Hz), the point estimates of absolute gain were universally reduced, and phase was increased under both conditions. In addition to an absence of regional differences, our findings indicate that alterations in CVRi independent of PaCO2 can alter cerebral pressure-flow dynamics. These findings are consistent with the concept of CVRi being a key factor that should be considered in the correct interpretation of cerebral pressure-flow dynamics as indexed using TFA metrics.

scholarly journals Carbon Dioxide Induced Changes in Cerebral Blood Flow and Flow Velocity: Role of Cerebrovascular Resistance and Effective Cerebral Perfusion Pressure

2015 ◽  
Vol 35 (9) ◽  
pp. 1470-1477 ◽  
Author(s):  
Frank Grüne ◽  
Stephan Kazmaier ◽  
Robert J Stolker ◽  
Gerhard H Visser ◽  
Andreas Weyland
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Flow Velocity ◽  
Cerebral Perfusion Pressure ◽  
Cerebral Perfusion ◽  
Perfusion Pressure ◽  
Cerebrovascular Resistance ◽  
Flow Pressure ◽  
Induced Changes ◽  
Zero Flow

In addition to cerebrovascular resistance (CVR) zero flow pressure (ZFP), effective cerebral perfusion pressure (CPPe) and the resistance area product (RAP) are supplemental determinants of cerebral blood flow (CBF). Until now, the interrelationship of PaCO2 -induced changes in CBF, CVR, CPPe, ZFP, and RAP is not fully understood. In a controlled crossover trial, we investigated 10 anesthetized patients aiming at PaCO2 levels of 30, 37, 43, and 50 mm Hg. Cerebral blood flow was measured with a modified Kety-Schmidt-technique. Zero flow pressure and RAP was estimated by linear regression analysis of pressure–flow velocity relationships of the middle cerebral artery. Effective cerebral perfusion pressure was calculated as the difference between mean arterial pressure and ZFP, CVR as the ratio CPPe/CBF. Statistical analysis was performed by one-way RM-ANOVA. When comparing hypocapnia with hypercapnia, CBF showed a significant exponential reduction by 55% and mean VMCA by 41%. Effective cerebral perfusion pressure linearly decreased by 17% while ZFP increased from 14 to 29 mm Hg. Cerebrovascular resistance increased by 96% and RAP by 39%; despite these concordant changes in mean CVR and Doppler-derived RAP correlation between these variables was weak ( r = 0.43). In conclusion, under general anesthesia hypocapnia-induced reduction in CBF is caused by both an increase in CVR and a decrease in CPPe, as a consequence of an increase in ZFP.

Effect of intracisternal phentolamine on cerebral blood flow after subarachnoid injection of blood

1976 ◽  
Vol 44 (3) ◽  
pp. 353-358 ◽  
Author(s):  
Albert N. Martins ◽  
Norwyn Newby ◽  
Thomas F. Doyle ◽  
Arthur I. Kobrine ◽  
Archimedes Ramirez
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Perfusion ◽  
Perfusion Pressure ◽  
Content Type ◽  
Cerebrovascular Resistance ◽  
Arterial Blood ◽  
Subarachnoid Injection ◽  
Ischemic Encephalopathy ◽  
Hydrogen Clearance

✓ The hydrogen clearance method was used to measure total and focal cerebral blood flow (CBF) in the monkey before and for 5 hours after a simulated subarachnoid hemorrhage (SAH). Some monkeys also received 0.2 to 1.0 mg/kg phentolamine intracisternally 3 hours after SAH. Results show that SAH did not change cerebrovascular resistance, but as cerebral perfusion pressure decreased, CBF fell transiently. Phentolamine injected intracisternally 3 hours after SAH produced a significant fall in arterial blood pressure; cerebrovascular resistance did not change but CBF decreased significantly. These data indicate that intracisternal phentolamine cannot be considered potentially useful to treat ischemic encephalopathy after SAH.

Carbon dioxide, critical closing pressure and cerebral haemodynamics prior to vasovagal syncope in humans

2001 ◽  
Vol 101 (4) ◽  
pp. 351-358 ◽  
Author(s):  
Brian J. CAREY ◽  
Penelope J. EAMES ◽  
Ronney B. PANERAI ◽  
John F. POTTER
Keyword(s):  
Carbon Dioxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vasovagal Syncope ◽  
Previous History ◽  
Normal Subjects ◽  
Cerebrovascular Resistance ◽  
Critical Closing Pressure ◽  
Closing Pressure

The cerebrovascular changes that occur prior to vasovagal syncope (VVS) are unclear, with both increases and decreases in cerebrovascular resistance being reported during pre-syncope. This study assessed the cerebrovascular responses, and their potential underlying mechanisms, that occurred before VVS induced by head-up tilt (HUT). Groups of 65 normal subjects with no previous history of syncope and of 16 patients with recurrent VVS were subjected to 70° HUT for up to 30min. Bilateral middle cerebral artery (MCA) cerebral blood flow velocities (CBFVs) were measured using transcranial Doppler ultrasound, along with simultaneous measures of MCA blood pressure, heart rate, and end-tidal and transcutaneous carbon dioxide concentrations. All 16 patients and 14 of the control subjects developed VVS during HUT. During pre-syncope, mean CBFV declined, due predominantly to a decrease in diastolic rather than systolic CBFV (decreases of 44.5±;19.8% and 6.3±;12.9% respectively; P < 0.0001). CO2 levels and indices of cerebrovascular resistance decreased during pre-syncope, while critical closing pressure (CrCP) increased to levels approaching MCA diastolic blood pressure before decreasing precipitously on syncope. Pre-syncopal changes were similar in syncopal patients and syncopal controls. CrCP, therefore, rises during pre-syncope, possibly related to progressive hypocapnia, and may account for the relatively greater fall in diastolic CBFV. Falls in cerebrovascular resistance, therefore, may be offset by rises in CrCP due to hypocapnia, leading to diminished cerebral blood flow during pre-syncope.

scholarly journals Association of Lactate Dehydrogenase with In-Hospital Mortality in Patients with Acute Aortic Dissection: A Retrospective Observational Study

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Huaping He ◽  
Xiangping Chai ◽  
Yang Zhou ◽  
Xiaogao Pan ◽  
Guifang Yang
Keyword(s):  
Blood Pressure ◽  
Lactate Dehydrogenase ◽  
Observational Study ◽  
Aortic Dissection ◽  
Hospital Mortality ◽  
Acute Aortic Dissection ◽  
Serum Lactate ◽  
Retrospective Observational Study ◽  
Serum Lactate Dehydrogenase ◽  
The Relationship

Background. Evidence regarding the relationship between serum lactate dehydrogenase (LDH) levels and in-hospital mortality in acute aortic dissection (AAD) patients is extremely limited. We aimed to investigate the relationship between LDH and in-hospital mortality in AAD patients. Methods. The present study was a retrospective observational study. A total of 1526 participants with acute aortic dissection were involved in a hospital in China from January 2014 to December 2018. The target-independent variable was LDH measured at baseline, and the dependent was all-cause mortality during hospitalization. Covariates involved in this study included age, gender, body mass index (BMI), hypertension, diabetes, smoking, stroke, atherosclerosis, systolic blood pressure (SBP), diastolic blood pressure (DBP), white blood cell (WBC), hemoglobin (Hb), alanine transaminase (ALT), aspartate aminotransferase (AST), albumin (ALB), creatinine (Cr), symptom, type of AAD (Stanford), and management. Results. The average age of 1526 selected participants was 52.72 ± 11.94 years old, and about 80.41% of them were male. The result of the fully adjusted model showed LDH was positively associated with in-hospital mortality in AAD patients after adjusting confounders (OR = 1.09, 95% CI 1.05 to 1.13). A nonlinear relationship was detected between LDH and in-hospital mortality in AAD patients after adjusting for potential confounders (age, gender, BMI, hypertension, diabetes, stroke, atherosclerosis, smoking, symptom, SBP, DBP, WBC, Hb, ALT, AST, ALB, Cr, type of AAD (Stanford), and management), whose point was 557. The effect sizes and the confidence intervals of the left and right sides of the inflection point were 0.90 (0.74–1.10) and 1.12 (1.06–1.19), respectively. Subgroup analysis in participants showed that the relationship between LDH and in-hospital mortality was stable, and all of the P value for the interaction in different subgroup were more than 0.05. Conclusions. The relationship between LDH and in-hospital mortality in AAD patients is nonlinear. LDH was positively related with in-hospital mortality when LDH is more than 557.

Cerebral blood flow autoregulation in early experimental S. pneumoniae meningitis

2007 ◽  
Vol 102 (1) ◽  
pp. 72-78 ◽  
Author(s):  
Michael Pedersen ◽  
Christian T. Brandt ◽  
Gitte M. Knudsen ◽  
Christian Østergaard ◽  
Peter Skinhøj ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Intracranial Pressure ◽  
Cerebral Perfusion ◽  
Perfusion Pressure ◽  
Arterial Blood ◽  
Norepinephrine Infusion ◽  
Intracisternal Injection ◽  
Cerebral Blood Flow Autoregulation

We studied cerebral blood flow (CBF) autoregulation and intracranial pressure (ICP) during normo- and hyperventilation in a rat model of Streptococcus pneumoniae meningitis. Meningitis was induced by intracisternal injection of S. pneumoniae. Mean arterial blood pressure (MAP), ICP, cerebral perfusion pressure (CPP, defined as MAP − ICP), and laser-Doppler CBF were measured in anesthetized infected rats ( n = 30) and saline-inoculated controls ( n = 30). CPP was either incrementally reduced by controlled hemorrhage or increased by intravenous norepinephrine infusion. Twelve hours postinoculation, rats were studied solely during normocapnia, whereas rats studied after 24 h were exposed to either normocapnia or to acute hypocapnia. In infected rats compared with control rats, ICP was unchanged at 12 h but increased at 24 h postinoculation (not significant and P < 0.01, respectively); hypocapnia did not lower ICP compared with normocapnia. Twelve hours postinoculation, CBF autoregulation was lost in all infected rats but preserved in all control rats ( P < 0.01). Twenty-four hours after inoculation, 10% of infected rats had preserved CBF autoregulation during normocapnia compared with 80% of control rats ( P < 0.01). In contrast, 60% of the infected rats and 100% of the control rats showed an intact CBF autoregulation during hypocapnia ( P < 0.05 for the comparison of infected rats at normocapnia vs. hypocapnia). In conclusion, CBF autoregulation is lost both at 12 and at 24 h after intracisternal inoculation of S. pneumoniae in rats. Impairment of CBF autoregulation precedes the increase in ICP, and acute hypocapnia may restore autoregulation without changing the ICP.

scholarly journals Model-derived assessment of cerebrovascular resistance and cerebral blood flow following traumatic brain injury

2010 ◽  
Vol 235 (4) ◽  
pp. 539-545 ◽  
Author(s):  
Michael L Daley ◽  
Nithya Narayanan ◽  
Charles W Leffler
Keyword(s):  
Traumatic Brain Injury ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Cerebral Perfusion ◽  
The State ◽  
Cerebrovascular Resistance ◽  
Fluid Percussion ◽  
Arterial Blood ◽  
Cerebrovascular Regulation

The published guidelines point out the need for the development of methods that individualize patient cerebral perfusion management and minimize secondary ischemic complications associated with traumatic brain injury. A laboratory method has been developed to determine model-derived assessments of cerebrovascular resistance (mCVR) and cerebral blood flow (mCBF) from cerebrovascular pressure transmission, and the dynamic relationship between arterial blood pressure (ABP) and intracranial pressure (ICP). The aim of this two-fold study is to (1) evaluate relative changes in the model-derived parameters of mCVR and mCBF with the corresponding changes in the pial arteriolar vascular parameters of pial arteriolar resistance (PAR) and relative pial arteriolar blood flow (rPABF); and (2) examine the efficacy of the proposed modeling methodology for continuous assessment of the state of cerebrovascular regulation by evaluating relative changes in the model-derived parameters of CBF and cerebrovascular resistance in relation to changes of cerebral perfusion pressure prior to and following fluid percussion brain injury. Changes of ABP, ICP, PAR, relative arteriolar blood flow (rPABF) and the corresponding model-derived parameters of mCBF and mCVR induced by acute hypertensive challenge were evaluated before and following fluid percussion injury in piglets equipped with cranial windows. Before fluid percussion, hypertensive challenge resulted in a significant increase of PAR and mCVR, whereas both rPABF and mCBF remained constant. Following fluid percussion, hypertensive challenge resulted in a significant decrease of PAR and mCVR and consistent with impaired cerebrovascular regulation. Hypertensive challenge significantly increased both rPABF and mCBF, which approximately doubled with increased CPP with correlation values of r = 0.96 ( P < 0.01) and r = 0.97 ( P ≤ 0.01), respectively. The assessment of model-derived cerebrovascular resistance and CBF with changes of CPP provides a means to monitor continuously the state of cerebrovascular regulation.

Response of human cerebral blood flow to +Gz accelerations

1994 ◽  
Vol 76 (5) ◽  
pp. 2114-2118 ◽  
Author(s):  
G. Ossard ◽  
J. M. Clere ◽  
M. Kerguelen ◽  
F. Melchior ◽  
J. Seylaz
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Arterial Blood Pressure ◽  
Transcranial Doppler ◽  
Cerebral Circulation ◽  
Cerebral Perfusion ◽  
Protective Mechanisms ◽  
Arterial Blood ◽  
Onset Rate

Intolerance symptoms associated with high sustained +Gz (head to foot) accelerations are attributed to lack of cerebral perfusion. To determine the response of cerebral circulation to +Gz stress, cerebral blood flow (CBF) was measured in humans with the transcranial Doppler method while cephalic arterial blood pressure was calculated simultaneously using a photoplethysmographic technique. Nine volunteers performed four randomized centrifuge runs at +2 to +5 Gz with a 0.4-G/s onset rate for 30 s. Compared with the control values, for +2-, +3-, +4-, and +5-Gz profiles, CBF was reduced by 19 +/- 7, 26 +/- 8, 49 +/- 26, and 61 +/- 29% (SD), respectively, at the end of the onset and by 18 +/- 4, 21 +/- 11, 27 +/- 7, and 47 +/- 29%, respectively, in the last 20 s of the plateau of acceleration. At the end of the onset and during the plateau of +Gz acceleration, CBF was less reduced than cephalic arterial blood pressure, suggesting that some mechanisms would occur to maintain cerebral perfusion under +Gz stress. These protective mechanisms are likely due to a siphon effect and/or an autoregulatory compensation.

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