Local cerebral blood flow in the conscious rat as measured with 14C-antipyrine, 14C-iodoantipyrine and 3H-nicotine.

Ohno, Kikuo; Pettigrew, K. D.; Rapoport, Stanley I.

doi:10.1161/01.str.10.1.62

Cited by 108 publications

(48 citation statements)

References 31 publications

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“…A double exponential curve was fitted to the relationship between arterial blood '4C-IAP concentration (Ca) and time (t) following the method of Ohno et al (1979) where:…”

Section: Autoradiographymentioning

confidence: 99%

The relationship between regional variations in blood flow and histology in a transplanted rat fibrosarcoma

Tozer

Lewis²,

Michałowski³

et al. 1990

Br J Cancer

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Summary The regional distribution of blood flow to the LBDS, fibrosarcoma, transplanted into the subcutaneous site in rats, was investigated using the readily diffusible compound '4C-iodo-antipyrine ('4C-IAP). Quantitative autoradiography was used to establish absolute values of specific blood flow F for 100 x 100 x 20 1sm adjacent tissue volumes of the unperturbed tumour. Mean blood flow to whole tumours was found to decrease with increase in tumour size. This relationship was abolished if blood flow was only measured in sections cut from the periphery of the tumours. Detailed analysis of a sub-group of tumours showed that blood flow to individual tumours was heterogeneous. The range of blood flow was large, indicating that mean blood flow to a whole tumour is a poor reflection of the blood perfusion pattern of that tumour. Necrotic tumour regions were usually very poorly perfused. With the exception of the smallest tumours studied, blood flow was lower in the centre of tumours than in the periphery. Necrosis also tended to develop centrally. However, the peripheral to central gradient of blood flow was apparent even when densely cellular, viable tumour regions and necrotic regions were analysed separately. The decrease in blood flow with tumour size was also apparent in densely cellular, viable tumour regions when analysed separately. Qualitative comparison of tumour histology and regional blood flow showed that there were areas of very low blood flow associated with viable tumour regions. Less common were areas of rather high blood flow associated with necrotic tumour regions. A complicated relationship exists between tumour histology and blood flow. The quantitative autoradiography technique is suitable for investigating the most poorly perfused and the most well perfused viable fractions of animal tumours which may limit the efficacy of different types of therapy.The blood flow to tumours plays an important role in their treatment. In radiotherapy, the efficacy of treatment depends upon cellular oxygen concentration which is governed by respiration rate and local blood flow. In chemotherapy, blood flow determines the efficiency of drug delivery. In hyperthermia, the temperature elevation achieved and the sensitivity of cells to heat is influenced by blood flow. Blood flow is therefore a critical parameter to measure both experimentally and clinically.It is known that blood flow to both transplanted animal tumours and to human tumours is heterogeneous (Chaplin et al., 1987;Ito et al., 1982;Vaupel & Frinak, 1980). Therefore global measurements may not be the most pertinent means of describing tumour blood flow. For instance, global measurements will include blood flow to necrotic tumour regions which are not relevant for therapy. For hyperthermia, a knowledge of high blood flow in discrete tumour regions would be important because these regions are the ones most likely to limit efficacy of treatment.Blasberg and colleagues used the inert, readily diffusible compound iodo-antipyrine to measure blood flow to tr...

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“…A double exponential curve was fitted to the relationship between arterial blood '4C-IAP concentration (Ca) and time (t) following the method of Ohno et al (1979) where:…”

Section: Autoradiographymentioning

confidence: 99%

The relationship between regional variations in blood flow and histology in a transplanted rat fibrosarcoma

Tozer

Lewis²,

Michałowski³

et al. 1990

Br J Cancer

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“…Regional CBF was measured using [14CJ-or [ I 25IJiodoantipyrine essentially as described by Ohno et al (1979). Animals were killed by decapitation 25 s after the start of a constant-rate intravenous infusion of tracer (20 f,lCi/ml at 1.0 milmin).…”

Section: Methodsmentioning

confidence: 99%

Studies on the Relationship between Cerebral Glucose Transport and Phosphorylation Using 2-Deoxyglucose

Hargreaves¹,

Planas

Cremer

et al. 1986

J Cereb Blood Flow Metab

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Summary: Regional rates of blood-brain glucose transfer and phosphorylation have been measured in anaesthe tized fasted and conscious fcd and fasted rats using a dual-label 2-deoxyglucose technique that exploits differ ences in the early-time distribution of analogue and na tive glucose between blood and brain. Regional cerebral blood flow was also measured in comparable groups of rats. Estimates of glucose influx in the anaesthetized group were compared with those calculated from pre viously published kinetic constants obtained using [14C]D-glucose as tracer. The close agreement of these two sets of results served to validate estimates of influx obtained using the glucose analogue. Comparisons be tween all three groups showed that regional rates of gluThis article exammes the distribution of tracer amounts of 2-deoxyglucose, relative to native glu cose, in individual brain regions during the first few minutes after intravenous injection. We previously described a method based on timed sequential in jections of 14C_ and 3H-labelled 2-deoxyglucose that gives estimates of glucose influx and phosphoryla tion simultaneously in the rat brain (Cunningham and Cremer, 198 I). This short-time dual-label 2-de oxyglucose technique involves the measurement of the distribution of tissue glucose relative to arterial plasma in the steady state and that of 2-deoxyglu cose relative to a plasma curve over a defined time course. We have now revised the model on which the estimates are based to incorporate blood flow.The estimate of the rate of glucose phosphoryla tion is based principally on the relationships be tween tissue glucose, 2-deoxyglucose, 2-deoxyglu cose phosphate, and a phosphorylation ratio (Crane et aI., 1978;Cunningham and Cremer, 1981). The Received March 20, 1986; accepted June 2, 1986. Address correspondence and reprint requests to Dr. V. J.Cunningham at MRC Toxicology Unit, Woodmansterne Road, Carshalton, Surrey SM5 4EF, England. 708cose influx were maintained at levels appropriate to the rate of cerebral glucose phosphorylation. This occurred despite wide variations in plasma glucose concentration. The results indicate that at least two factors are involved in the adaptation of glucose supply to meet metabolic de mand. One is related to blood flow, and probably reflects changes in the surface area of the capillary endothelium perfused. The second involves changes in the blood brain barrier permeability to glucose and could reflect changes in the density of functioning glucose transporters within capillary endothelial cell membranes. Key Words: Cerebral glucose phosphorylation -2-Deoxyglucose Early-time distribution-Glucose-Modulation-Re gional blood-brain transport.estimate of the rate of glucose influx, however, is a more complex function of the relative distribution volumes of glucose and analogue. We therefore wished to validate the estimates obtained for glu cose influx using 2-deoxyglucose. Cunningham et at. (1986) measured glucose influx across the blood -brain barrier in fasted anaesthetized rats us...

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“…Tissue concentrations of lAP were ob tained by the tissue-sampling technique of Ohno et al (1979). The brain:blood partition coefficient of lAP was set at 0.8 (Sakurada et aI., 1978).…”

Section: Measurement Of Cbfmentioning

confidence: 99%

“…By measuring CBF in homogenates of brain re gions with the 14C-iodoantipyrine (lAP) technique (Ohno et al, 1979), we sought to determine whether, under carefully controlled conditions, electrical stimulation of DMRF will also increase rCBF in rats, and if so, whether the effect is restricted only to cerebral cortex, and whether the response is me diated by intrinsic pathways in the brain. Prelimi nary reports of portions of this study have been made (ladecola et aI., 1981, 1982).…”

mentioning

confidence: 99%

Global Cerebral Vasodilatation Elicited by Focal Electrical Stimulation within the Dorsal Medullary Reticular Formation in Anesthetized Rat

Iadecola

Nakai

Arbit

et al. 1983

J Cereb Blood Flow Metab

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Summary:We examined the effects of electrical stimu lation of a restricted area of the dorsal medullary reticular formation (DMRF) on regional cerebral blood flow (CBF) in anesthetized (by chloralose), paralyzed (by curare) rats. CBP was measured in tissue samples by the Kety prin ciple, with 14C-iodoantipyrine as indicator. Stimulation of DMRF elicited a widespread, significant increase in CBP in 12 of 13 areas. The increase in flow was greatest in cerebral cortex, up to 240% of control. However, it was also substantially increased in selected regions of telen cephalon, diencephalon, mesencephalon, and lower brainstem, but not cerebellum. In contrast, electricalIt has been believed for many years that the brainstem may control cerebral circulation. The ev idence has been derived largely from studies that have assessed the effects on cerebral blood flow (CBF) of locally altering neuronal activity by focal electrical stimulation (Reis, 1979). Such studies have demonstrated that modification of brainstem func tion may, in fact, alter CBF, thereby suggesting that the CNS can regulate its own circulation through intrinsic neuronal systems.These investigations, however, left two issues un resolved. First, since CBF was measured either across the entire brain (Langfitt and Kassell, 1968; Meyer et aI., 1969 Meyer et aI., , 1971Lang and Zimmer, 1974) or only qualitatively estimated from restricted brain regions, usually cerebral cortex (lngvar, 1958;Molnar and Szanto, 1964; Vern et aI., 1981; Reis et aI., 1982), they did not establish whether the evoked changes in flow were localized or global. Second, 270stimulation of the midline (interstitial nucleus of the me dial longitudinal fasciculus) I mm medial to the DMRF did not change CBF. The increase in CBP evoked by DMRF stimulation persisted after transection of the spinal cord at CI or cervical sympathetic trunk. We conclude that excitation of neurons originating in or passing through the DMRF can elicit a potent and virtually global increase of CBF. The effect appears to be mediated by intrinsic pathways of the central nervous system.

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Local cerebral blood flow in the conscious rat as measured with 14C-antipyrine, 14C-iodoantipyrine and 3H-nicotine.

Abstract: Local

Cited by 108 publications

References 31 publications

The relationship between regional variations in blood flow and histology in a transplanted rat fibrosarcoma

The relationship between regional variations in blood flow and histology in a transplanted rat fibrosarcoma

Studies on the Relationship between Cerebral Glucose Transport and Phosphorylation Using 2-Deoxyglucose

Global Cerebral Vasodilatation Elicited by Focal Electrical Stimulation within the Dorsal Medullary Reticular Formation in Anesthetized Rat

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