The presence of hyperglycemia prior to stroke or cardiac arrest can increase neuronal damage caused by brain ischemia. Acute hyperglycemia shows this effect in animal models of stroke. However, chronic hyperglycemia and chronic hyperglycemia with additional acute elevation of blood glucose are more common premorbid states for stroke patients. The effect of chronic hyperglycemia on regional cerebral blood flow (rCBF) is unclear but blood flow changes may play a role in this ischemic cell damage. We measured rCBF in awake restrained rats that had chronic hyperglycemia induced by treatment with streptozotocin. This was compared to that measured in rats made acutely hypergh/cemic by injecting glucose into the peritoneal space. rCBF was measured in 17 brain regions using [ u C]iodoantipyrine. During chronic hyperglycemia, when plasma glucose was 29 ^.m/ml, rCBF was decreased and a regional distribution of this effect was noted; 9 hindbrain regions showed a mean flow decrease of 14% while forebraln regions demonstrated less flow reduction. Acute elevation of plasma glucose during normoglycemia or superimposed on chronic hyperglycemia produced flow reductions of 7% for each 10 /xm/mJ increment in plasma glucose up to 60 /xm/ml. Both chronic and acute hyperglycemia are associated with decreased rCBF and the mechanism for this effect does not appear to adapt to chronic hyperglycemia. (Stroke 1987; 18:52-58) C LINICAL studies suggest that hyperglycemia is a risk factor for stroke 1 and that it increases brain injury during stroke or cardiac arrest.2 "4In animal models of stroke, acute hyperglycemia before ischemia increases mortality 3 and the number of neurons that die. 6 "* After transient ischemia, hyperglycemia increases and prolongs postischemic hyperemia 89 and enhances the heterogeneity of reperfusion. 10However, in normal animals an acute elevation of plasma glucose is associated with decreased regional cerebral blood flow (rCBF). 10 " This effect could limit compensatory blood flow mechanisms during an ischemic event.In clinical situations hyperglycemia, whether iatrogenic or the result of stroke itself, 12 is seldom as acute or as severe as that induced in animal models of stroke. Also, diabetics are frequently exposed to acute increases in blood glucose superimposed on a background of chronic hyperglycemia. Little is known about the effect of chronic hyperglycemia on rCBF. For these reasons we measured rCBF in awake restrained rats that had a moderate chronic hyperglycemia produced by treatment with streptozotocin. We found that chronic hyperglycemia was associated with decreased rCBF. Also, a specific regional distribution of this effect was noted with hindbrain regions manifesting CBF decreases during chronic hyperglycemia. Materials and Methods The isotope 4-iodo|7V-methyl-14 C]antipyrine, 53 mCi/mmol, was obtained from Amersham, Arlington Heights, El. Streptozotocin, 2-deoxy-2-([methylnitrosoamino]carbonyl)-amino(-

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The presence of hyperglycemia before brain ischemia increases stroke-related morbidity and mortality in experimental animals and humans. However, little is known of the effect of hyperglycemia on regional cerebral blood flow (rCBF). Acute hyperglycemia was induced in awake but restrained rats by intraperitoneal injection of 50% D-glucose. Regional flow was determined using [14C]iodoantipyrine and quantitative autoradiography. Elevation of plasma glucose from 11 to 39 mM was associated with a 24% reduction in rCBF when compared with controls that received normal saline. Intraperitoneal D-mannitol produced an elevation of plasma osmolality equivalent to that observed with glucose. However, rCBF was only reduced by 10%. Hyperglycemia appears to produce a global decrease in rCBF in awake rats that cannot be completely explained by the attendant increase in plasma osmolality. If a similar influence is present during brain ischemia, hyperglycemia could extend areas of critical flow limitation.

SUMMARY Cerebral blood flow autoregulation (CBFA) to changes in perfusion pressure has not been previously reported in the rat. A modification of the Kety and Schmidt technique employing I33Xenon was used to measure cerebral blood flow (CBF) in paralyzed adult Sprague Dawley rats passively ventilated with 70% nitrous oxide and 30% oxygen. At a mean arterial blood pressure (MABP) of 121 ± 19 mm Hg, and a mean arterial Pco 2 of 36.2 ± 2.9 mm Hg, mean CBF was 103 ± 22 ml/min/100 gm of brain. CBF responses to hypercarbia were 4.9 ml/min/100 gm per mm Hg change in arterial Fco 2 . CBF was measured during steady state levels of hypo-and hypertension induced by phlebotomy, or by intravenous metaraminol, over the MABP range of 48-205 mm Hg. From a MABP of 80 to 160 mm Hg, CBF remained nearly constant, indicating the presence of CBFA. However, when MABP exceeded 160 mm Hg, CBF became pressure dependent, indicating a "breakthrough" of autoregulation in acute severe hypertension.CEREBRAL BLOOD FLOW autoregulation (CBFA) denotes the adaptive reaction whereby blood flow to the brain is maintained nearly constant despite variations in perfusion pressure.1 In most mammalian species, including man, CBFA has been characterized within the mean arterial blood pressure (MABP) range of approximately 70 to 150 mm Hg.2 ' 5 However, cerebral circulatory responses to blood pressures beyond this range in acute hypertension have not been extensively studied. Some investigators have recently reported that cerebral autoregulatory mechanisms fail at high perfusion pressures, with a so-called "breakthrough" of CBFA taking place. 59Most studies of the cerebral circulation have been carried out in man or in large experimental animals. More recently, CBF has also been studied in the most widely used laboratory animal, the albino rat, by a variety of methods, and values for basal CBF under conditions of normotension have been reported.10 "" However, pressure-flow relationships for the cerebral circulation have not been defined in this species. In the present study we have measured CBF in rats during induced alterations in arterial blood pressure. We have examined a wide range of systemic pressures, paying particular attention to the state of cerebral circulation during acute hypertension. Methods Animal PreparationSprague-Dawley rats of both sexes, weighing 300-600 gm, were employed in this study. Each rat was rapidly tracheotomized under ether anesthesia, paralyzed with tubocurarine (0.5 mg/kg, administered subcutaneously), and passively ventilated with a mixture of 70% nitrous oxide and 30% oxygen by a small animal respirator. Atropine (0.05 mg/kg) was injected subcutaneously to minimize tracheobronchial secretion. Ventilatory rate and tidal volume were adjusted to ensure arterial blood normoxia and normocarbia. The caudal artery was exposed and catheterized with a 30 gauge Teflon catheter. This catheter served to monitor arterial blood pressure with a pressure transducer (Statham, Model P23Dc), and to allow anaerobic withdrawal of arterial blo...

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Cerebral blood flow (CBF) and cerebral metabolic rates (CMR) were studied in newborn dogs during insulin-induced hypoglycemia. Pups were anesthetized, paralyzed, and artificially ventilated with a mixture of 70% nitrous oxide and 30% oxygen to maintain normoxia and normocarbia. Experimental animals were given regular insulin (0.3 units/gm IV); controls received normal saline. CBF was determined using a modification of the Kety-Schmidt technical employing 133Xe as indicator. Arteriovenous differences for oxygen, glucose, lactate, and beta-hydroxybutyrate (beta-OHB) were also measured, and CMRO2 and CMRsubstrates calculated. Two groups of hypoglycemic dogs were identified; those in which blood glucose levels were greater than 0.5 mM (group 1), and those in which they were less than 0.5 mM (group 2). CBF did not change significantly from control values of 23 +/- 10 ml/min/100 g (mean +/- S.D.) at both levels of hypoglycemia. Similarly, hypoglycemia did not alter CMRO2 significantly from its initial level of 1.05 +/- 0.37 ml O2/min/100 g. Glucose consumption in brain during normoglycemia accounted for 95% of cerebral energy supply with minimal contributions from lactate (4%) and beta-OHB (0.5%). During hypoglycemia, CMRglucose declined by 29 and 52% in groups 1 and 2, respectively, while CMRlactate increased to the extent that this metabolite became the dominant fuel for oxidative metabolism in brain. The cerebral utilization of beta-OHB was unaltered by hypoglycemia. The findings indicate that insulin-induced hypoglycemia in the newborn dog is associated with an increase in cerebral lactate utilization, supplementing glucose as the primary energy fuel and thereby preserving a normal CMRO2. These metabolic responses may contribute to the tolerance of the immature nervous system to the known deleterious effects of hypoglycemia.

Merges the latest results obtained by the holonic manufacturing systems (HMS) consortium with the latest developed standards for platform interoperability released by the Foundation for Intelligent Physical Agents (FIPA) to propose a novel e‐business model: the holonic e‐enterprise (HE). The HE extends both the HMS and FIPA models. On one side it extends the holonic manufacturing paradigm with one top level, the inter‐enterprise one. On the other side it extends the multi‐agent system (MAS) paradigm to the hardware (physical machine) level.