SUMMARY In cats, the early development of Iscbemlc brain edema was studied 1 to 4 noun after transorbital occlusion of the left middle cerebral artery (MCA). Two groups of animals were compared: those in which blood flow in the territory of the MCA decreased below the threshold of 10-15 ml/100 g/mln (critical ischemia) and those in which it remained above this level (non-critical ischemia).In animals with critical ischemia, water content in the cortex of the MCA territory increased from 80.7 ± 0.4 to 83.0 ± 0 3 vol. % (means ± SE) within 4 h. Edema was associated with an increase in tissue osmolality by 16-22 mosm/kg w.w., and a rise of sodium from 262 ± 9 to 454 ± 13 meq/kg d.w. and a decrease of potassium from 442 ± 20 to 305 ± 32 meq/kg d-w. The sodium/potassium ratio rose from 0.60 ± 0.03 to 1.55 ± 0.17. The water and electrolyte disturbances were accompanied by a major shift of extracellular fluid into the intracellular compartment, as evidenced by the increase in cortical impedance from 282 to 660 ohm/cm within 2 h. According to the Maxwell equation, this reflects a narrowing of the extracellular space from 19.8 to 11.4%. Brain volume was continuously monitored using an induction transducer; swelling began within a few minutes of vascular occlusion, and it continued throughout the 4 h observation period. During this time the blood-brain barrier remained intact as evidenced by the absence of Evans blue staining. Edema was associated with disturbances of the energy producing metabolism, but there was DO strict correlation with either lactate or the concentration of high energy phosphates.In animals without critical ischemia, i.e. in which blood flow remained above 10-15 ml/100 g/min, edema was absent despite a distinct deterioration of the energy state of the brain. Edema was also absent in the border zone, in the territory of the posterior cerebral artery and in the contralateral hemisphere of animals with both critical and non-critical ischemia.It is concluded that the early ischemic brain edema following middle cerebral artery occlusion is of the c>totoxic type, that it develops at a flow rate below 10-15 ml/100 g/min, and that it is not strictly correlated with the energy state of the brain.

SUMMARY In 48 cats the left middle cerebral artery was occluded under light barbiturate anesthesia using a transorbital approach. The animals were kept alive for 1, 2, and 4 hours after vascular occlusion. Regional cerebral blood flow was measured by the intracardiac microsphere injection technique before ischemia, 15 min after the onset of ischemia, and at the end of the experiments. The density of regional ischemia was correlated with EEG changes and with the electrolyte, water and metabolite content of the same tissue samples in which blood flow was assessed. In the territory of the occluded middle cerebral artery, cortical blood flow decreased from 41.4 ± 3.8 to 21J ± 4.0 ml/100 g/min (means ± SE), the actual flow rate depending on the individual efficacy of collateral blood supply. At flow rates below 10-15 ml/100 g/min, ischemia involved more than 50% of the middle cerebral artery territory, water and electrolyte homeostasis was severely disturbed and iscbemic brain edema developed. Adenosine triphosphate decreased to about 60% of the control value at flow rates below 40 ml/100 g/min, but it remained at this level down to flow rates as low as 5 ml/100 g/min. EEG intensitybut not EEG frequency -decreased in parallel with blood flow, indicating that with increasing density of ischemia an increasing portion of the excitable neuropil was inhibited.The development of ischemic brain edema determined the further progression of ischemia. When blood flow decreased below the threshold for water and ion disturbance, ischemia was progressive (critical ischemia), but an amelioration of flow occurred in animals in which flow remained above this level (non-critical ischemia). In the contralateral hemisphere the EEG, blood flow, water and electrolyte content did not change significantly during the initial few hours of ischemia. Diaschisis, in consequence, was not a prominent feature during the early phase of infarct development.

Local cerebral glucose utilization assayed by the [14C]deoxyglucose ([14C]DG) method and calculated by means of its operational equation with values for the rate constants and lumped constant determined in rats under physiological conditions remains relatively stable with variations in arterial plasma glucose concentration within the normoglycemic range. Large changes in arterial plasma glucose level may, however, significantly alter the values of these constants and lead to artifactual results. Values for the lumped constant have been measured and reported for a wide range of arterial plasma glucose concentrations ranging from hypoglycemia to hyperglycemia in the rat (Schuier et al., 1981; Suda et al., 1981; Pettigrew et al., 1983). In the present study we have redetermined the rate constants in rats with arterial plasma glucose levels clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM) by a glucose clamp technique. The rate constants for the transport of DG from plasma to brain, K1*, and its phosphorylation in tissue, k3*, were found to decline with increasing plasma glucose levels, while the rate constant for its transport back from brain to plasma, k*2, remained relatively unchanged from its value in normoglycemia. These rate constants were used together with the previously determined values for the lumped constants to calculate local rates of cerebral glucose utilization in three groups of rats in which arterial plasma glucose levels were clamped at approximately 350, 450, and 550 mg/dl (i.e., 19, 25, and 31 mM). Average glucose utilization in the brain as a whole was unchanged in hyperglycemia from the values calculated in normoglycemic rats with the standard normal set of constants. Changes in the rate of glucose utilization were found, however, in the hypothalamus, globus pallidus, and amygdala during hyperglycemia.

The lumped constant of the deoxyglucose method was determined by the steady-state, model-independent method in the brain of normal conscious rats with arterial plasma glucose concentrations varying from normoglycemia (i.e., 8 mM) to hyperglycemia (i.e., 31 mM). The lumped constant for brain was found to decrease very gradually with increasing arterial plasma glucose concentration from a value of approximately 0.45 in the midnormoglycemic range (i.e., 7-8 mM) to approximately 0.38 at 28-31 mM. 3-O-[14C]Methylglucose was used to assess the distribution of glucose within the brain structures in hyperglycemia; the results indicated that the glucose concentration, and therefore also the values for the lumped constant, remain relatively uniform in hyperglycemia with arterial plasma glucose concentrations as high as 34 mM. The values for the lumped constant for rat brain determined in the present studies were combined with those previously determined in this laboratory for hypoglycemia and normoglycemia by the same method to provide a single source for the values for the lumped constant to be used over the full range of arterial plasma glucose concentrations. In several rats the lumped constant for cephalic extracerebral tissues was also evaluated in parallel with those for the brain. The lumped constant for the cephalic extracerebral tissues was found to be about twice that for brain and to be unaffected by changes in arterial plasma glucose levels.

We evaluated the effects of breathing 35% stable xenon in 65% oxygen on regional cerebral blood flow and the electroencephalogram in 20 normal volunteers. We measured blood flow in 32 brain regions over both hemispheres with the xenon-133 intravenous injection technique in two protocols. In the first protocol (n = 10), a baseline study was followed by a second study during 5 minutes of breathing stable xenon; in the other protocol (n=8), the baseline study was followed by a second study after 5 minutes of breathing stable xenon. Two volunteers were excluded due to excessive movements during the inhalation of stable xenon. Some of the remaining 18 volunteers had varying alterations of consciousness accompanied by electroencephalogram changes. After stable xenon inhalation the electroencephalogram returned to normal within 2-3 minutes. During stable xenon inhalation mean±SD PECO 2 dropped significantly from 39.4±4.4 to 33J±5.4 mm Hg in the first protocol and from 39.4±2.6 to 34.8±4.1 mm Hg in the second protocol due to hyperventilation in 13 volunteers. Mean regional cerebral blood flow increased significantly by 13.5-25.4% without correction for PECO 2 . In the first protocol regional cerebral blood flow increased by >L2% in 11-14 (depending on the flow parameter) of the 20 hemispheres. In the second protocol regional cerebral blood flow increased by >12% in 9-13 of the 16 hemispheres. We conclude that cautious interpretation is necessary in the assessment of regional cerebral blood flow with 35% xenon-enhanced computed tomography. {Stroke 1991;22:182-189)

A comparison of local cerebral blood flow estimates with the microsphere and the 4-[N-methyl-14C]iodoantipyrine ([14C]IAP) techniques has been performed in cats. Good correlation of [14C]IAP with microsphere flow estimates in the gray matter was found. In the white matter, however, [14C]IAP flow estimates were consistently lower than microsphere flow estimates. Error analysis of both techniques and comparison with previous studies suggest that peculiarities of white matter arterial vasculature with preferential microsphere accumulation may lead to this discrepancy. Microspheres did not interfere with flow as shown by the normal appearance of subsequent [14C]IAP autoradiograms. The number of microspheres seen on autoradiograms was used for an estimate of microvessels blocked by spheres and found to be negligible. The study also demonstrates that [14C]IAP is not diffusion limited up to the observed flow values of 2 ml.g-1.min-1. Both techniques might be used together for a combination of their respective advantages, which are temporal and spatial resolution for microsphere and [14C]IAP, respectively.

No abstract

A method was developed to measure simultaneously the rate constants for glucose influx and glucose efflux, and the Michaelis-Menten constant (KM) and maximal velocity (Vmax) for glucose transport across the blood-brain barrier (BBB) in any selected brain area. Moreover, on the basis of a mathematical model, the local perfusion rate (LPR) and local unidirectional glucose transport rate (LUGTR) are calculated in terms of parameters of the time-activity curves registered over different brain regions; 11C-methyl-D-glucose (CMG) is used as an indicator. The transaxial distribution of activity in the organism is registered using dynamic positron-emission tomography (dPET). The method was used in 4 normal subjects and 50 patients with ischemic brain disease. In normals, the rate constant for CMG efflux was found to be 0.25 +/- 0.04 min-1 in the cortex and 0.12 +/- 0.02 min-1 in white matter. In the cortex, the KM was found to be 6.42 mumol/g and the Vmax was 2.46 mumol/g per minute. The LUGTR ranged from 0.43 to 0.6 mumol/g per minute in the cortex, and from 0.09 to 0.12 mumol/g per minute in white matter. The LPR was calculated to be 0.80-0.98 ml/g per minute for the cortex and 0.2-0.4 ml/g per minute for white matter. In patients with stroke, the ischemic defects appeared to be larger in CMG scans than in computed x-ray tomography (CT) scans. Prolonged reversible ischemic neurological deficit was associated with a significant fall in the LUGTR but no change in the LPR in the corresponding cerebral cortex. Normal LUGTR and significantly decreased LPR were registered in a patient with progressive occlusion of the middle cerebral artery. In a patient with transient ischemic attacks, a slightly reduced LPR and a disproportionally reduced LUGTR were observed before operation. After extra- and intracranial bypass surgery, the LPR became normal, whereas the LUGTR increased but did not achieve normal values.