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Cerebral Blood Flow Autoregulation During Hypobaric Hypotension Assessed by Laser Doppler Scanning

December 1994
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 14(6):1100-5

December 1994
14(6):1100-5

DOI:10.1038/jcbfm.1994.144

Source
PubMed

Authors:

Axel Heimann

Johannes Gutenberg-Universität Mainz

Peter T. Ulrich

Hospital zum Heiligen Geist Frankfurt am Main, Germany

Hypobaric hypotension was used to reduce systemic blood pressure in rats below the lower threshold of CBF autoregulation to evaluate a new laser Doppler (LD) "scanning" technique. Spontaneously breathing male Wistar Kyoto rats (n = 8) were anesthetized with chloral hydrate and the head fixed in a stereotaxic head holder. A cranial window with intact dura mater was introduced to assess local CBF (lCBF) by LD. One stationary probe served to detect rapid flow changes, whereas the second probe was used to sample lCBF recordings from many cortical locations by means of a stepping motor-controlled micromanipulator to obtain lCBF frequency histograms. Advantages are an improved spatial resolution together with the easy detection of low-flow areas and a better comparison of data from individual experiments. Arterial blood pressure was stepwise reduced by exposing the lower body portions to subatmospheric pressures (hypobaric hypotension), thus avoiding the use of drugs or heparinization. The lower threshold of CBF autoregulation was detected by "scanning" at arterial pressures between 50 and 46 mm Hg, with low-flow spots occurring immediately. The data suggest LD scanning as a method suited particularly for studies where lCBF inhomogeneities are expected, e.g., the ischemic penumbra or sinus vein thrombosis.

Time course of focal CBF (ICBF) of an individual ex periment measured by the stationary laser Doppler (LD). Lowering MABP by hypobaric hypotension below a threshold of 60 mm Hg induced a proportional reduction of ICBF (y =-34 + 1.65x-0.01X2; r = 0.915). There was, however, a considerable flow variation at each pressure level in individ ual animals. Inset: Time course of MABP for the pressure classes chosen.

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Local CBF (ICBF) as assessed by stationary (a) and scanning (b) laser Doppler (LD). Data are shown as box plots (median with 5 and 95% percentiles) for all MABP classes, and biological zero as determined after death. Under condi tions with MABP variations between 60 and 85 mm Hg, ICBF remained on a stable plateau. Below a threshold of <50 mm Hg, ICBF was reduced with decreasing blood pressure. Note the earlier statistical significance obtained with LDscan. LDstat values were lower than LDscan since measuring sites free of visible vasculature had been chosen for the stationary probe, whereas LDscan data were calculated from medians of scanned histograms. Arrows indicate statistically significant differences (analysis of variance on ranks for repeated mea sures, p < 0.05).

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. Intended and actually measured arterial blood pressures (mm Hg) before and during hypobaric hypotension (n = 8)

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   

        

     

     

     

         

         

  

      

 

        

    

        

        

        

    

        

        

     

     

     

       

     

   

       

     

      

       

      

    

      

      

     

       

     

    

      

        

   

       

        

   



  



        





        

      

        

   

     

     

         

      

        

     

      

  

  

     

        

   

 

        

 

       

   

   

 

      

 

 

       

 

       

       

      

   

      

       



      

   

      

      

   

      

     



      

 

   

 

  

    

           

       

      

       

   

      

     

       

     

     

      

         

     

        

 

         

            

   

      

        

       

         

      

       

       

         

     

        

    

 

        

       

        

         

      

    

      

   

         

        

    

      

       

     

     

       

        

       

  

         

 

           



     

      

          

        

       

       

       



        

           

      

   

   

 

        

      



 

        

   

         

    

    

      

         

         

     

 

   

   

       

  

         

        

       

         

      

       

     

       

    

    





   

   

 

     

    

   

      

 



  

     

     

     

      

        

    

            

   

 



 









  























       

    

        

    

  

       

        

     



 

      

    

 



        

  

    

      

     

     













 







 









 









 













 





 

  



 

 

 

 

 

  

        



    



          

       



       

         

     

         

 

        

 









































       

 

       

   



      

       

      

        

      

      

         

   

    

    

     

       

        

       

        

        

 

      

 

     

       

    

       

      

    

        

    

     

         

   

    

        

      

   

         



  

      

 

      

     

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

         

     

       

       

      

       

       

  

        



       

   

       

  

 

    

        



       

      



   



       

      

       

      

      

       

        

   

      

        



       

   

      

 

       



 

      



     

 

       



       

    

 

      

      

      

        

   

      

    

      

 

       

     



 

     

      

      

         

      

       









      

 

 

      

       

   

 



 



 

             







  

 

 

 

 

 





  



 









   I

 



 



 

              







   

 I

 

 

  



   

 



  



            



      

     

     

      

 

  

       

  



        

       

 

      

    

      

      

       

  



       

 

   

       

   

     



   

        

      

        





     

 

 



     





 

 

 

      

     

  

   

   

    



   



    

    

    

      

    

  

    

    

   

    

     

  

     

  

  

     

 



   

     

   

 

  

    

   

     





      

 

      

   

      

        

      

   

        

 

   

      

    



       

         

     

        

     

     



      

      

   

        

  

      





 



         

        



        

     

    

         

      



    

 

   

   

     



       



       

      

     

     

  



  



       

 

       

        

  

        

       

   



         

       

       

    

 

       



         

    

   

        

   

         



       

        

      

 

        

      

      

 

    

  

    

         

   

        

 

       

     

     

     

       

 

      

       

 

       

Einfluß hyperton-/hyperonkotischer Lösungen auf die posttraumatische kortikale Durchblutung des Gehirns und das sekundäre Nekrosewachstum bei fokaler kortikaler Kälteläsion

Article

Nov 2007

David H. Friedrich

Variations of brain endothelial nitric oxide synthase concentration in rat and mouse cortex

Article

Jan 2010
NITRIC OXIDE-BIOL CH

No information exists on the differences of eNOS concentration in brain tissue, [eNOS]br, between animals during normal and hypotensive blood pressure and both between and within animals during moderate hypotension. To address these questions, we modified a commercially available enzyme-linked immunosorbent assay (ELISA) kit for determining murine [eNOS]br since no method exists to measure [eNOS]br. Optimization of the kit ELISA procedure using brain cortex homogenates from 3 normotensive rats and 1 wild-type and 1 eNOS−/− (ko) mouse included recovery evaluation for each sample and the use of an “eNOS-free” homogenate calibrator diluent obtained from a mutant eNOS-ko mouse. Initial spike-and-recovery values of 12.5–27% suggesting a substantial sample matrix effect were improved with lipid removal treatment to 37.3% and to 70% with 1:20 dilution of the sample. Calibration standards prepared using eNOS-free buffer increased recovery values to 78% in micro-punch samples. The optimized ELISA was used in micro-punch (<1 mg) brain cortex samples from 6 hypotensive rats. Whole brain [eNOS]br varied considerably from 5–11 fmol/mg wet weight and was different between normo- and hypotensive animals (p = 0.023). The variability of [eNOS]br due to moderate hypotension in micro-punch rat brain cortex samples was composed of both between (24%) and within (76%) animal components. The differences and variability of [eNOS]br between normo- and hypotensive animals, and between and within hypotensive animals suggests the potential utility of its measurement for investigations of cerebrovascular physiology and that [eNOS]br itself could be an important factor in cerebrovascular regulation.

Laser Doppler Imaging of Activation-Flow Coupling in the Rat Somatosensory Cortex

Article

Jan 2000

Activation-flow coupling (AFC) provides a physiological basis for mapping cerebral activation using cerebral blood flow (CBF) as a surrogate marker for neuronal function. Laser Doppler offers a minimally invasive approach for measuring changes in cerebral blood flow but the spatial resolution of this technique is limited by the number of individual probes that can be used. Recently, laser Doppler imaging (LDI) scanners, which use computer-driven optics to scan and measure LD changes in two dimensions, have successfully measured flow changes in the exposed cortex of animals. Here we demonstrate the use of an LDI device through a thinned skull to determine the spatiotemporal characteristics of AFC in α-chloralose anesthetized rats in response to electrical forepaw stimulation. The spatial and temporal characteristics of the AFC response measured by LDI are in agreement with prior results obtained using a single LD probe. These results suggest a promising role for LDI in the characterization of the spatiotemporal characteristics of AFC in animal models and possibly for intraoperative monitoring in the human brain.

A Scanning Technique to Measure Regional Cerebral Blood Flow and Oxyhemoglobin Level

Article

Jun 2001

Quantitative Topography of the Hemodynamic-Oxidative Metabolic Interrelation by Multispot Measurement Approach in Rat Ischemia Models

Chapter

Jan 2001

We applied the multispot measurement approach for both laser Doppler (LD) and a microspectrophotometric method to measure local cerebral blood flow (1CBF) and local tissue hemoglobin oxygenation (IHbO2). We demonstrated that the current technology permits in vivo observation, allowing us to establish a close topographical relation between CBF and HbO2. We measured 1CBF by LD flowmetry and tissue HbO2 by a microspectrophotometric method at multiple corresponding locations using a “scanning” technique that employs a computer-controlled micromanipulator. CBF and HbO2 data from predefined locations were correlated to the topographical situation and then arranged in a three-dimensional (3D) image using xyz triplet columns for a mesh and scatter plot. The quantitative topography of the hemodynamic-metabolic interrelation was studied using two experimental models: ischemia/reperfusion (experiment 1), and sinus-vein thrombosis (experiment 2) in rat brain. Using the scanning technique we determined misery and luxury flow (postischemic hyperperfusion) compared with oxygen metabolism in experiment 1 and drainage of desaturated blood via collateral pathways, although detected as flow, in experiment 2. The technique, including the scanning procedure, is useful for showing sequential changes of the hemodynamic-metabolic interrelations of the brain cortex. The technique could reveal phenomena previously undetected by traditional techniques.

Heterogeneous Autoregulatory Capacity in the Rat Cerebral Cortex as Observed by a Novel Two-Dimensional Flow Mapping Technique

Chapter

Jan 2001

Cerebral blood flow (CBF) autoregulation in a small area of the cerebral cortex (region of interest, ROI) was examined by a novel optical method recently developed by the authors. A two-dimensional (2-D) map of mean transit time (MTT) was created during hemorrhagic hypotension in nine rats. The total average MTT in the control group ranged from 1.43 to 2.30 s (mean ± SD 2.09 ± 0.43 s), increased to 3.29 ± 0.84 s at a mean blood pressure of 50 mmHg, and decreased to 1.53 ± 0.37 s after reinfusion of blood. When 47 average CBF values obtained during nine experiments were plotted against the mean arterial blood pressure, autoregulatory changes were broadly observed above about 70 mmHg. The 2-D relative flow maps, calculated as 2-D MTTcontrol/2-DMTThypotension revealed that the autoregulation in the ROI was not homogeneous when the blood pressure decreased to 75 mmHg: some microregional areas remained at the control flow level, whereas others showed a decrease in CBF at the same perfusion pressure. We hypothesize that the well-autoregulating areas might represent the functionally active parts or functional units of the cortex. One possibility is that blood flow is redistributed to the functionally active portion from other resting portions of the cortical capillary bed when the reduced perfusion pressure challenges the cerebral circulation.

A Rat Model to Study Damage and Defense Mechanisms Under Penumbra Conditions

Chapter

Jan 1999

The destiny of the ischemic penumbra - defined as a territory of critically reduced blood flow in the close neighborhood of an ischemic core - determines outcome from stroke. Currently, the pathophysiology of the penumbra is studied mainly in rat models with occlusion of the middle cerebral artery. Here, we propose another rat model with distinct advantages. It produces a large territory of critical flow reduction in the cortex of one hemisphere without the presence of an infarct core; this model is suited to study mediator mechanisms that may turn the penumbra into necrotic tissue. It is produced by occluding one carotid artery and, in addition, reducing arterial pressure to 50 mmHg using the hypobaric hypotension technique. Cortical flow is assessed by laser Doppler scanning. Induction of cortical spreading depression is used to evaluate whether spreading-depression-induced increases of cortical blood flow are absent as an indicator of penumbra conditions.

Visualization of Regional Cerebral Blood Flow Dynamics during Cortical Venous Occlusion using Laser Speckle Contrast Imaging in a Rat Model

Article

Jul 2015

Cerebral venous ischemia (CVI) is a rare but potentially significant complication of neurosurgical procedures. However, it is still unclear how cerebral venous occlusion (VO) affects regional cerebral blood flow (rCBF) dynamics. To elucidate its pathophysiology in detail, we examined the real-time perfusion dynamics during adjacent vein occlusions using laser speckle contrast imaging (LSCI) in a rat 2-vein occlusion model. Two cortical veins were occluded photochemically using rose Bengal dye in 6 male Wistar rats; rCBF was measured in real time with an LSCI before and after VO. Regions of interest were defined between the 2 veins (A) and on the opposite side of the first occluded vein (B) on semi-quantitative pseudocolor images for off-line analysis. Histopathologic evaluation was performed 3 days after the procedure to assess the extent of infarction. LSCI revealed a stepwise reduction in CBF, with a sudden decrease just after the first vein occlusion (∼20%) and a further decrease after the second (∼30%). Significant differences were observed between rCBF dynamics within regions of interest A and B (P = .0004). All rats exhibited infarcts in the superficial cerebral cortex histopathologically. This is the first report of LSCI specifically applied to the study of CVI. The extensive real-time measurement with high temporal and spatial resolution revealed the stepwise reduction in rCBF during sequential VO and the ensuing infarcts. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Die Bedeutung des zerebralen Perfusionsdruckes in der Behandlung des schweren Schädel-Hirn-Traumes

Thesis

Nov 2003

Stefan Kroppenstedt

Die Höhe des optimalen zerebralen Perfusionsdruckes nach schwerem Schädel-Hirn-Trauma wird kontrovers diskutiert. Während im sogenannten Lund-Konzept ein niedriger Perfusionsdruck angestrebt und die Gabe von Katecholaminen aufgrund potentieller zerebraler vasokonstringierender und weiterer Nebeneffekte vermieden wird, befürwortet das CPP-Konzept nach Rosner eine Anhebung des zerebralen Perfusionsdruckes, wenn notwendig unter intravenöser Gabe von Katecholaminen. Vor diesem Hintergrund galt es, in einem experimentellen Schädel-Hirn-Trauma- Modell der Ratte (Controlled Cortical Impact Injury) den Bereich des optimalen zerebralen Perfusionsdruckes nach traumatischer Hirnkontusion zu ermitteln und den Effekt von Katecholaminen auf den posttraumatischen zerebralen Blutfluss und die Entwicklung des sekundären Hirnschadens zu untersuchen. Die wesentlichen Ergebnisse dieser Arbeit lassen sich wie folgt zusammenfassen: In der Akutphase nach Hirnkontusion liegt der Bereich des zerebralen Perfusionsdruckes, welcher die Entwicklung des Kontusionsvolumens nicht beeinflusst, zwischen 70 und 105 mm Hg. Eine Senkung des Perfusionsdruckes unterhalb bzw. Anhebung oberhalb dieser Schwellenwerte vergrößert das Kontusionsvolumen. Die Anhebung des Blutdruckes mittels intravenöser Infusion von Dopamin oder Noradrenalin führt sowohl in der Frühphase als auch in der Spätphase nach Trauma (4 Stunden bzw. 24 Stunden nach kortikaler Kontusion) zu einem signifikanten Anstieg im kortikalen perikontusionellen Blutfluss und in der Hirngewebe-Oxygenierung. Die durch Anhebung des zerebralen Perfusionsdruckes auf über 70 mm Hg induzierte Verbesserung des posttraumatischen zerebralen Blutflusses bewirkte jedoch keine Reduzierung der Hirnschwellung. Für eine Katecholamin-induzierte zerebrale Vasokonstriktion nach kortikaler Kontusion gibt es keinen Anhalt. Um die Entwicklung des sekundären Hirnschadens nach kortikaler Kontusion zu minimieren, sollte der zerebrale Perfusionsdruck nach traumatischem Hirnschaden nicht unterhalb 70 mm Hg liegen. Eine Anhebung des Perfusionsdruckes auf über 70 mm Hg erscheint nicht notwendig oder vorteilhaft zu sein. Wenn notwendig, kann sowohl in der Früh- als auch Spätphase nach Trauma der zerebrale Perfusionsdruck mittels intravenöser Gabe von Katecholaminen angehoben werden.

Cessation of Diastolic Cerebral Blood Flow Velocity: The Role of Critical Closing Pressure

Article

Nov 2013
NEUROCRIT CARE

Reducing cerebral perfusion pressure (CPP) below the lower limit of autoregulation (LLA) causes cerebral blood flow (CBF) to become pressure passive. Further reductions in CPP can cause cessation of CBF during diastole. We hypothesized that zero diastolic flow velocity (FV) occurs when diastolic blood pressure becomes less than the critical closing pressure (CrCP). We retrospectively analyzed studies of 34 rabbits with CPP below the LLA, induced with pharmacologic sympathectomy (N = 23) or cerebrospinal fluid infusion (N = 11). Basilar artery blood FV and cortical Laser Doppler Flow (LDF) were monitored. CrCP was trended using a model of cerebrovascular impedance. The diastolic closing margin (DCM) was monitored as the difference between diastolic blood pressure and CrCP. LDF was recorded for DCM values greater than and less than zero. Arterial hypotension caused a reduction of CrCP (p < 0.001), consistent with decreased wall tension (p < 0.001) and a drop in intracranial pressure (ICP; p = 0.004). Cerebrospinal infusion caused an increase of CrCP (p = 0.002) accounted for by increasing ICP (p < 0.001). The DCM was compromised by either arterial hypotension or intracranial hypertension (p < 0.001 for both). When the DCM reached zero, diastolic FV ceased for a short period during each heart cycle (R = 0.426, p < 0.001). CBF pressure passivity accelerated when DCM decreased below zero (from 1.51 ± 0.51 to 2.17 ± 1.17 % ΔLDF/ΔmmHg; mean ± SD; p = 0.010). The disappearance of diastolic CBF below LLA can be explained by DCM reaching zero or negative values. Below this point the decrease in CBF accelerates with further decrements of CPP.

Autoregulation of Cerebral Blood Flow in Experimental Focal Brain Ischemia

Article

Full-text available

Jun 1990

The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood-flow (CBF) in areas of focal cerebral ischemia was studied in 15 spontaneously hypertensive rats (SHRs) anesthetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flowmetry during manipulation of SAP with I-norepinephrine (hypertension) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipulations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of greater than 30% of preocclusion values. In areas where ischemic CBF was less than 30% of preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was less than 15% of baseline (6% change in CBF with each 10% change in SAP). These findings demonstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the severity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia.

Continuous Measurement of Cerebral Cortical Blood Flow by Laser-Doppler Flowmetry in a Rat Stroke Model

Article

Full-text available

Nov 1989

Laser-Doppler flowmetry (LDF), a new method allowing instantaneous, continuous, and noninvasive measurements of microcirculatory blood flow in a small tissue sample, was evaluated for its accuracy in monitoring regional cerebral blood flow (rCBF) in the cortical microcirculation after focal cerebral ischemia. Wistar and spontaneously hypertensive rats (SHR, n = 19) were subjected to permanent occlusion of the middle cerebral and common carotid arteries. Absolute rCBF in a tissue sample of the ischemic hemisphere was measured autoradiographically with [14C]iodoantipyrine as a tracer and compared to rCBF measured by LDF. Additionally, the percent change in rCBF between baseline and ischemic values was compared for both methods. Absolute rCBF values recorded with LDF correlated poorly (r = 0.54) with [14C]iodoantipyrine measurements. In contrast LDF readings expressed as a percentage of ischemic vs. preocclusion readings (relative LDF readings) correlated very well (r = 0.91) with the percent change in [14C]iodoantipyrine measurements. We conclude that LDF does not provide accurate measurements of absolute rCBF values but this method allows accurate measurements of changes in rCBF due to induction of focal cerebral ischemia.

Effect of the Calcium Antagonists Felodipine and Nimodipine on Cortical Blood Flow in the Spontaneously Hypertensive Rat

Article

Feb 1990

We studied the effect of the dihydropyridine calcium antagonists felodipine and nimodipine on perfusion of the cerebral cortex in the spontaneously hypertensive rat (SHR). Nimodipine and felodipine were infused in equipotent doses in chloralose-anaesthetized SHR. During the infusion of a low and an intermediate dose of felodipine, mean arterial blood pressure was lowered to 90.5 ± 1.5 and 67.1 ± 2.9% of the control level. The nimodipine infusion lowered mean arterial pressure to 85.7 ± 2.0 and 59.7 ± 2.4% of the control level. At these pressures, cortical perfusion as measured by a laser Doppler flow technique increased to 123.5 ± 6.9 and 130 ± 5.4% of the control level during the felodipine infusion and to 114.0 ± 1.6 and 122.3 ± 3.2% of the control level during the nimodipine infusion. When these results were compared by covariance analysis of variance, felodipine induced a significantly greater change in coretical perfusion. At the highest dose of felodipine and nimodipine there was no significant difference in cortical perfusion between the two drugs. The administration of felodipine induced a decrease in cerebrovascular autoregulation. However, this impairment of cerebrovascular autoregulation is not likely to trigger cerebral hypoperfusion. Thus, for a mean arterial pressure of 55 mmHg, the laser Doppler-measured cortical flow was, if anything, elevated after felodipine administration.

Laser Doppler assessment of brain microcirculation: Effect of systemic alterations

Article

May 1989
Am J Physiol

There is a need for new technical approaches whereby the cerebral microcirculation can be easily and continuously assessed. The objective of this study was to determine whether laser-Doppler (LD) flowmetry can be utilized to assess changes in cerebral cortical blood flow and to determine whether changes in blood perfusion measured by LD flowmetry correlate with simultaneously measured changes in flow measured by H2 clearance in cats or with changes in pial arteriolar diameter measured with a microscope in rabbits equipped with a closed cranial window. In the rabbit experiments a 0.84-mm-diam LD probe was inserted through a cranial window port, and in the cat experiments the probe was fixed adjacent to the H2 probe. The probe was fixed at a distance of 1-2 mm from the cortical surface, where it and its associated electronics detect changes in blood cell velocity and blood volume within a tissue volume of approximately 1 mm3. Volume and velocity are multiplied to provide a flow signal. When cerebral blood flow in cats was decreased by hyperventilation-induced hypocapnia and increased by norepinephrine-induced hypertension, the percent changes in LD flow and H2 clearance flow changed linearly (r = 0.94, slope = 0.97). When arterial PCO2 was increased from 28 to 48 mmHg in the rabbit experiments, the pial arterioles dilated 19 +/- 4% (mean +/- SE) and LD flow increased by 74 +/- 9%, LD flow changes which would be predicted by a third power relationship of diameter to flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Validation of laser-Doppler flowmetry in measurement of spinal cord blood flow

Article

Sep 1989
Am J Physiol

Laser-Doppler flowmetry (LDF) is a non-invasive method for continuous on-line monitoring of microvascular blood flow. LDF has previously been validated with established methods in various tissues, yet its validity and resolution in the central nervous system (CNS) remain unclear. We compared LDF with the microsphere method (MS) using two independent laser probes placed on the dorsal lumbar spinal cord (L5 laminectomy) of anesthetized rabbits (n = 9). After base-line flow measurements, spinal cord blood flow (SCBF) was increased (up to 50%) with phenylephrine (10-80 micrograms.kg-1.min-1 iv) and decreased (up to 50%) with chlorisondamine (10 mg/kg iv) or other stimuli. The percentage changes of lumbar SCBF and vascular resistance (VR) from the base line obtained by LDF and MS excellently agreed (rBF = 0.86, rVR = 0.94, P less than 0.0001). LDF estimated also the absolute SCBF values parallel to MS (r = 0.77, P less than 0.001). In conclusion, the validity of LDF in estimating the SCBF and dynamic changes of BF and VR is confirmed. Therefore, LDF may prove useful for monitoring CNS microcirculation in normal or pathophysiological states.

Repeated measurements of cerebral blood flow in rats. Comparisons between the hydrogen clearance method and laser Doppler flowmetry

Article

Oct 1988

Changes in cerebral blood flow (CBF), in chloralose-anaesthetized spontaneously hypertensive rats, were measured simultaneously with the hydrogen clearance (HC) method and laser Doppler flowmetry (LDFM) in order to examine the correlation between results obtained with the two techniques. To induce changes in CBF the rats were bled and CBF measured at different levels of mean arterial pressure. As would be expected, with the platinum electrode at the depth of about 1 mm in the somatosensory cortex, HC gave biexponential curves reflecting clearance in two distinct compartments. During control situation the HC method gave the following values (mean +/- SE, n = 20, ml min-1 100 g-1): fast (fCBF) 158.6 +/- 11.5, slow (sCBF) 29.1 +/- 1.6 with a weighted mean flow (mCBF) of 83.3 +/- 7.4. These fCBF and sCBF values correspond well to those of others obtained with [14C]iodoantipyrine autoradiography in the cerebral cortex and corpus callosum, and better than the results of other studies using HC in rats. Our results, comparing data from HC and LDFM, show a linear relationship between relative values of blood flow changes, the coefficients being 0.658, 0.876 and 0.878 for the correlation between the LDFM data and relative changes in fCBF, sCBF and mCBF, respectively. All three regression lines were significantly different from the line of identity. Much of the discrepancy between the two methods may be related to limitations inherent in each of them, despite efforts to minimize their effects. Thus the depth sensitivity of LDFM in the brain may be greater than expected. In conclusion, the laser Doppler method seems, nevertheless, to be most useful for continuous estimations of changes in cerebral blood flow.

Cerebral blood flow in rats during physiologic and humoral stimuli

Article

May 1981

The technique for estimating cerebral blood flow (CBF) in anesthetized rats by injecting 133Xe into the internal carotid artery represents a potentially useful and inexpensive model for screening cerebral vascular responses to pathophysiological and pharmacological stimuli. We have examined associated neuropathology, the validity and the reproducibility of the method, and made comparisons of initial slope estimates of CBF with those obtained by stochastic analysis. Initial slope estimates (CBF = 1.62 +/- 0.04 ml min-1g-1, X +/- SE, N = 38) were linearly related to stochastic measurements (CBF = 1.42 +/- 0.09 ml min-1g-1, N = 6), and overestimated mean CBF by about 15%. A reactivity to CO2 of 0.05 ml min-1g-1 per mm Hg, and an auto-regulation range of 70 to 180 mm Hg were found. CBF responses to the intra-arterial infusion of aminergic drugs were determined before and after opening of the blood-brain barrier with hypertonic urea. Serotonin reduced CBF after, but not before, the administration of urea. Acetylcholine increased CBF when the barrier was intact, the effect being augmented when the barrier was disrupted; these responses were reduced by atropine. Histamine increased CBF only after barrier opening, and this response was attenuated by the H2-receptor antagonist, metiamide. These studies indicate that initial slope estimates of CBF derived in rats from intracarotid 133Xe injection, which represents an inexpensive and simplified approach for screening cerebral circulatory adjustments, may facilitate the characterization of stimuli affecting CBF.

Dirnagl U, Thoren P, Villringer A, Sixt G, Them A, Einhaupl KMGlobal forebrain ischemia in the rat: controlled reduction of cerebral blood flow by hypobaric hypotension and two-vessel occlusion. Neurol Res 15:128-130

Article

May 1993

We developed and characterized a model of global forebrain ischaemia in rats, permitting control of CBF at any desired ischaemic level with minimum surgery and without anticoagulation. Both common carotid arteries are occluded temporarily and systemic arterial pressure is lowered by pooling venous blood by lower body negative pressure with a cheap suction device. By measuring rCBF continuously (laser-Doppler-flowmetry) and regulating systemic arterial pressure, the model was used to automatically control cortical rCBF at predetermined ischaemic levels at 50, 30, 15, and 5% of normal rCBF (n = 5). When both common carotid arteries were occluded and systemic arterial pressure was lowered to 55 mmHg with hypobaric hypotension (n = 5), cortical CBF always fell to less than 5% of normal rCBF (n = 5). Prompt recirculation was achieved after reopening of the carotid arteries and return to normobaric body pressure. Hypobaric hypotension with bilateral common carotid occlusion requires only carotid surgery and measurement of systemic arterial pressure; it produces global forebrain ischaemia without anticoagulation as a true step function type insult. If rCBF is measured continuously, the model can be used to control ischaemic CBF to predetermined values.

Laser Doppler perfusion imaging by dynamic light scattering

Article

May 1993

Imaging of tissue perfusion is important in assessing the influence of peripheral vascular disease on microcirculation. This paper reports on a laser Doppler perfusion imaging technique based on dynamic light scattering in tissue. When a laser beam sequentially scans the tissue (maximal area approximately 12 cm *12 cm), moving blood cells generate Doppler components in the back-scattered light. A fraction of this light is detected by a remote photodiode and converted into an electrical signal. In the signal processor, a signal proportional to the tissue perfusion at each measurement point is calculated and stored. When the scanning procedure is completed, the system generates a color-coded perfusion image on a monitor. A perfusion image is typically built up of data from 4,096 measurement sites, recorded during a time period of 4 min. This image has a spatial resolution of about 2 mm * 2 mm. A theory for the system inherent amplification factor dependence on the distance between individual measurement points and detector is proposed and correction measures are presented. The performance of the laser Doppler perfusion imager was evaluated using a flow simulator. The correlation coefficient between the estimated flow parameter and the perfusion through a mechanical flow simulator was calculated to r = 0.996. To assess the sampling depth of the laser beam, light scattering in tissue was simulated by a Monte Carlo technique. The average sampling depth for skin tissue was calculated to 200-240 microns, depending on the blood content.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral blood flow alterations in a rat model of cerebral sinus thrombosis

Article

Apr 1993

Outcome from sinus vein thrombosis is very variable, with symptoms from headache to coma. Experimental findings suggest that an involvement of cortical veins is necessary to affect the cerebral microcirculation. Laser Doppler flowmetry was used to investigate the regional and temporal changes in local cortical blood flow after experimental occlusion and thrombosis of the superior sagittal sinus and tributary cortical veins in rats. Thrombosis was induced by slow injection of kaolin-cephalin suspension after frontal and caudal ligation of the sagittal sinus in rats. Local cerebral blood flow was measured by laser Doppler flowmetry and correlated with parenchymal damage found 24 hours after induction of thrombosis. Local cerebral blood flow 1 hour after sinus occlusion and induction of thrombosis had decreased to 60.92 +/- 29.05% (p < 0.01); however, there was a large variability among individual animals. Only five of 12 rats showed histological damage and intracerebral hemorrhages 24 hours after induction of thrombosis. A subgroup analysis revealed that parenchymal damage occurred in concurrence with reduced blood flow values after sinus ligation and injection of the thrombogenic material. Sinus thrombosis alone, without alteration of blood flow, did not cause tissue necrosis. The data support the contention that sinus vein thrombosis evolves gradually, with major symptoms occurring only if the thrombus expands from the sinus into bridging and cortical veins. Collateral venous outflow pathways are thereby occluded, and local blood flow may become reduced to and below the ischemic threshold.

Cerebral Blood Flow Autoregulation During Hypobaric Hypotension Assessed by Laser Doppler Scanning

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