Lack of Capillary Recruitment in the Brains of Awake Rats during Hypercapnia

Göbel, U.; Klein, Burkhard; Schröck, Helmut; Kuschinsky, Wolfgang

doi:10.1038/jcbfm.1989.72

Cited by 106 publications

(50 citation statements)

References 21 publications

(10 reference statements)

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“…(3) The oxygen diffusibility (L) was assumed not to change at any measured blood flow level, because of the absence of capillary recruitment in human brain (Gobel et al, 1989;Kuschinsky and Paulson 1992;Vogel et al, 2004). At the highest oxygen extraction fraction compatible with normal oxygen consumption (E O2 E0.55, see Discussion), P mit O2 E0.…”

Section: Calculationsmentioning

confidence: 99%

“…The analysis revealed a physiological mitochondrial tension of 8.5 mm Hg, on assumption of constant oxygen diffusion conditions, including absent recruitment of capillaries. The absence is well supported for physiologic conditions, but it is unclear whether it extends to nonphysiologic states below the threshold of flowlimitation of oxygen consumption (Gobel et al, 1989, Kuschinsky andPaulson, 1992;Vogel et al, 2004).…”

Section: Effect Of Indomethacin On Cmr Omentioning

confidence: 99%

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Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

Gjedde

Johannsen

Cold

et al. 2005

J Cereb Blood Flow Metab

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The reactions of cerebral metabolism to imposed changes of cerebral blood flow (CBF) are poorly understood. A common explanation of the mismatched CBF and oxygen consumption (CMR O 2 ) during neuronal excitation holds that blood flow rises more than oxygen consumption to compensate for an absent oxygen reserve in brain mitochondria. The claim conversely implies that oxygen consumption must decline when blood flow declines. As the prevailing rate of reaction of oxygen with cytochrome c oxidase is linked to the tension of oxygen, the claim fails to explain how oxygen consumption is maintained during moderate reductions of CBF imposed by hyperventilation (hypocapnia) or cyclooxygenase (COX) inhibition. To resolve this contradiction, we extended the previously published oxygen delivery model with a term allowing for the adjustment of the affinity of cytochrome c oxidase to a prevailing oxygen tension. The extended model predicted constant oxygen consumption at moderately reduced blood flow. We determined the change of affinity of cytochrome c oxidase in the extended model by measuring CBF in seven, and CMR O 2 in five, young healthy volunteers before and during COX inhbition with indomethacin. The average CBF declined 35%, while neither regional nor average CMR O 2 changed significantly. The adjustment of cytochrome c oxidase affinity to the declining oxygen delivery could be ascribed to a hypothetical factor with several properties in common with nitric oxide.

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Section: Calculationsmentioning

confidence: 99%

Section: Effect Of Indomethacin On Cmr Omentioning

confidence: 99%

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

Gjedde

Johannsen

Cold

et al. 2005

J Cereb Blood Flow Metab

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“…25 In brief, 125 Ci/kg body wt iodo [ 14 C]antipyrine (Biotrend) was infused with an increasing infusion rate for 1 minute. Parallel to this, 12 to 16 timed arterial blood samples were taken for the determination of the time course of the arterial iodo[ 14 C]antipyrine concentration.…”

Section: Autoradiographymentioning

confidence: 99%

Early Delineation of Ischemic Tissue in Rat Brain Cryosections by High-Contrast Staining

Vogel

Möbius

Kuschinsky

1999

Stroke

Self Cite

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Background and Purpose-After short periods of ischemia, commonly used staining methods yield only moderate differences in optical contrast between normal and damaged brain tissue when gray-scale images are used for computer-assisted image analysis. We describe a high-contrast silver infarct staining (SIS) method that allows an early delineation of ischemic tissue as soon as 2 hours after middle cerebral artery occlusion (MCAO) in rat brain cryosections. Methods-Rats were subjected to permanent MCAO for 2, 4, 6, and 48 hours. The optical densities were quantified in nonischemic white and gray matter and in damaged tissue from gray-scale images of serial sections with the use of a video camera-based image analyzing system. SIS, hematoxylin-eosin, Nissl, and nitroblue tetrazolium stainings were performed in cryosections, and 2,3,5-triphenyltetrazolium hydrochloride (TTC) staining was performed in unfrozen vibratome sections. In addition, the range of reduced cerebral blood flow (CBF) in areas demarcated by SIS was determined in iodo[ 14 C]antipyrine autoradiograms of adjacent cryosections. Results-At all times after MCAO, only SIS showed significantly (PϽ0.01) lower optical densities in damaged than in normal brain tissue for both white and gray matter. TTC staining was as effective as SIS 6 and 48 hours after MCAO. The tightest correlation between areas of reduced SIS and of reduced CBF was found at a mean ischemic CBF of 22.3 mL/100 g per minute. This corresponds to a CBF range of 0 to 44 mL/100 g per minute in areas of reduced SIS. Conclusions-In contrast to other staining methods, SIS allows a reliable delineation of ischemic brain tissue (core plus penumbra) from nonischemic white and gray matter of rat brain cryosections as soon as 2 hours after MCAO. (Stroke. 1999;30:1134-1141.)

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“…In support of this suggestion, Gobel et al (1989) and Villringer et al (1991) also found that raising arte rial CO2 did not increase the number of plasma perfused or plasmatic capillaries, and Raichle et al (1976) reported that elevating the rate of blood flow by altering P aco2 did not enlarge the P S products of three BBB-permeable alcohols plus water.…”

Section: Capillary Recruitment Hypothesismentioning

confidence: 89%

Nicotine Raises the Influx of Permeable Solutes across the Rat Blood—Brain Barrier with Little or No Capillary Recruitment

Chen

Wei

Bereczki

et al. 1995

J Cereb Blood Flow Metab

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Summary: Nicotine (1.75 mg/kg s.c.) was administered to rats to raise local CBF (ICBF) in various parts of the brain, test the capillary recruitment hypothesis, and de termine the effects of this increase in lCBF on local solute uptake by brain. lCBF as well as the local influx rate constants (K I) and permeability-surface area (P S) pro ducts of e4C]antipyrine and [14C]-3-0-methyl-D-glucose (30MG) were estimated by quantitative autoradiography in 44 brain areas. For this testing, the finding of signifi cantly increased PS products supports the capillary re cruitment hypothesis. In 17 of 44 areas, nicotine treat ment increased lCBF by 30-150%, K I of antipyrine by 7-40%, KI of 30MG by 5-27%, PS product of antipyrine by 0-20% (mean 7%), and PS product of 30MG by 0-23% (mean 8%). Nicotine had no effect on blood flow or influx in the remaining 27 areas. The increases in lCBF and K IThe major purposes of blood circulation to and through the capillaries of the brain most certainly are the delivery of nutrients to cells and ligands to receptors and the removal from the parenchyma of locally produced metabolites , messenger mole cules, reactive species such as free radicals, and heat energy. In most instances, useful or meaning ful increases and decreases in blood flow would therefore be expected to be linked to changes in one or more of these functions. 687of antipyrine were significant, whereas those in KI of 30MG and in PS for both antipyrine and 30MG were not statistically significant. The lack of significant changes in P S products implies that in brain areas where nicotine increased blood flow: (a) essentially no additional capil laries were recruited and (b) blood flow within brain cap illary beds rises by elevating linear velocity. The KI re sults indicate that the flow increase generated by nicotine will greatly raise the influx and washout rates of highly permeable materials, modestly elevate those of moder ately permeable substances, and negligibly change those of solutes with extraction fractions of <0.2, thereby pre serving the barrier function of the blood-brain barrier.

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Lack of Capillary Recruitment in the Brains of Awake Rats during Hypercapnia

Cited by 106 publications

References 21 publications

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

Early Delineation of Ischemic Tissue in Rat Brain Cryosections by High-Contrast Staining

Nicotine Raises the Influx of Permeable Solutes across the Rat Blood—Brain Barrier with Little or No Capillary Recruitment

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