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Biomedical subjects

M Reivich

Publications and source records attributed to M Reivich.

195 records · Page 11Linked to original sources
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Correlation between glucose utilization and metabolite levels during focal ischemia in cat brain.

Focal ischemia was produced in cat brain by occluding the middle cerebral artery. After 60 min of ischemia the rate of glucose utilization, as measured by the uptake of [14C] deoxyglucose ([14C]DG), was correlated with tissue levels of ATP, phosphocreatine, and lactate measured in the same regional samples. Ischemia caused local increases of [14C]DG uptake which were associated with mild to moderate anaerobic perturbations of metabolite levels. Altered metabolite levels also occurred in regions in which the rate of glucose consumption was not markedly different from that of the non-ischemic hemipshere. In addition, there were regions with decreased [14C] DG uptake which invariably were depleted of ATP and phosphocreatine. Thus, suppression of glucose metabolism was restricted to the most severely ischemic areas, where the delivery of glucose may be rate-limiting.

Adenosine Triphosphate↗
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Use of 123I and 14C in a double radionuclide autoradiographic technique for simultaneous measurement of LCBF and LCMRgl. Theory and method.

We have developed an autoradiographic technique for the simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral metabolic rate for glucose (LCMRgl) using 123I-iodoantipyrine and 14C-2-deoxyglucose respectively. By exploiting the different half-lives of 123I and 14C, 13.0 hours versus 5730 years, we produce 2 autoradiographic images. The first is predominantly a result of the 123I and the second is predominantly from the 14C. Because of the impracticality of making 123I standards, it was necessary to determine the constant which relates the ability of 123I, with respect to 14C, to expose Kodak SB-54 film, so that the 123I exposure could be quantified using 14C standards. Subtraction equations can then be used to solve for the local 123I and 14C concentrations. The technique was validated in conditions simulating a 12-fold decoupling of flow and metabolism and the standard deviation of error in measuring tracer concentrations was less than 6%. It was then used to measure these parameters in the normal awake rats and values obtained agreed well with published values from single radionuclide studies. The technique is expected to be useful in the simultaneous measurement of LCBF and LCMRgl in various physiologic or pathologic states, including those with significant decoupling of flow and metabolism. In addition, by using other tracers labelled with 123I and 14C, other parameters can be measured concurrently.

Animals↗
PubMedDate not supplied

Regional cerebral glucose metabolism during and after bilateral cerebral ischemia in the gerbil.

Cerebral metabolic rate for glucose (CMRG) was measured using the 14C-deoxyglucose technique in a stroke model of the gerbil produced by bilateral common carotid artery occlusion. During 30 minutes of ischemia, 14C-deoxyglucose uptake in the brain was increased along the border zone between the ischemic and nonischemic area and decreased in the ischemic areas. During the early stage of reperfusion (2 or 3 to 30 minutes), CMRG increased 50 to 150% in the cerebral cortex, caudoputamen and thalamus and 270 to 320% in the hippocampus, globus pallidus and amygdala. During the late stage of reperfusion (15 to 45 minutes), heterogeneity of CMRG appeared in the cerebral cortex, caudoputamen and thalamus. CMRG decreased to less than 50% of the control value in the cerebral cortex but remained at 200 to 300% of control in the hippocampus, globus pallidus and amygdala. The latter structures exhibited a larger and more protracted increase in glucose metabolism than the other structures most probably due to the histological vulnerability to ischemia of these structures. The relationship between the transient increase of the glucose metabolism and cell function is discussed.

Animals↗
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Correlation between brain surface potassium and glucose utilization after bilateral cerebral ischemia in the gerbil.

The correlation between cerebral glucose utilization and brain surface potassium concentration (BS-K+) was studied during reperfusion following bilateral cerebral ischemia in the gerbil. Cerebral glucose utilization rate was measured by the 14C-2-deoxyglucose method and BS-K+ was continuously monitored by a potassium sensitive membrane electrode. BS-K+ increased from 3.0 +/- 0.6 mM (mean +/- S.D.) before ischemia to 58.7 +/- 17.3 mM 30 minutes after the occlusion of both common carotid arteries. The rate of decline of BS-K+ after release of occlusion differed between animals. Glucose utilization rate in the cerebral cortex immediately under the potassium electrode was low but homogeneous in 7 animals while in 5 animals the metabolic pattern was heterogeneous with areas of both low and high glucose metabolism. The former animals exhibited a fast recovery of potassium flux while the latter animals showed a slow recovery. Glucose utilization rate and potassium half recovery time were linearly correlated. These studies suggest that the reason that potassium flux may not recover rapidly in postischemic brain tissue is due to the lack of sufficient energy for a rapid re-establishment of the ion gradient across the cell due to the inefficient energy production of anaerobic glycolysis.

Animals↗
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Changes in cerebral blood flow and recovery from acute stroke.

We prospectively studied 14 patients with acute cerebral infarctions using serial 133Xenon inhalation cerebral determination (133Xe-rCBF), scored neurological examinations, and neuropsychological testing. All patients underwent the same battery of tests at 3 days, 1 week, 2 weeks, and 4 weeks after cerebral infarction to determine the prognostic value of early rCBF studies and the chronological relationship of changes in rCBF to clinical status. Baseline rCBF within 3 days of symptoms of acute stroke did not correlate with clinical neurological outcome (r = -0.17, p less than 0.30; r = -0.18, p less than 0.28, for the two indices of rCBF used). Among the 11 patients demonstrating neurological recovery, 7 improved at 1 week, significantly before increases in rCBF (p less than 0.05). We conclude that early baseline rCBF does not predict clinical outcome in patients with acute cerebral infarctions and that return of neurological function precedes rather than follows increases in rCBF.

Aged↗
PubMedDate not supplied

Cerebral glucose metabolism during the recovery period after ischemia--its relationship to NADH-fluorescence, blood flow, EcoG and histology.

Local cerebral glucose utilization (lCMRgl), NADH fluorescence, cerebral blood flow (CBF), electrocortical activity (ECoG) and histology were studied during a 4 hr recovery period following 2 hrs of left middle cerebral artery (MCA) occlusion in cats. Changes in relative reduced pyridine nucleotides and CBF were measured by fluororeflectometry, ECoG was obtained from the left middle ectosylvian gyrus (MEG), and lCMRgl was measured at the end of the recovery period autoradiographically with 14-C-2-deoxyglucose. A sham group was comprised of 4 cats. The ten animals subjected to the stroke were classified into 3 groups based on the mean amplitude of the ECoG at the end of the ischemic period. At the end of the recovery period, the relative reduced pyridine nucleotides showed a 22.5% oxidation (oxidation of NADH), a 66.2% reduction (reduction of NAD) and a 3.0% reduction compared to the sham group in the severe, moderate and mild groups, respectively. LCMRgl of the left MEG in the severe group was 64.2% of the corresponding sham value, whereas lCMRgl in the moderate and mild groups were 124.8% and 132.0% of the sham, respectively. CBF at the end of the recovery period ranged from 28.1% to 83.0% of the sham value, although there was no significant difference among these groups. Histologically, a large portion of the neurons in the left MEG in the severe group showed ischemic neuronal changes, while the damage was less severe in the moderate and mild groups. On the basis of these data, it is suggested that a relative substrate deficiency and/or a loss of mitochondrial enzymatic pool size may occur in the animals comprizing the severe group. Conversely, anaerobic glycolysis may be activated in the moderate group, while the mild group exhibits an increase in glucose metabolism that is most likely aerobic. A gradient in the magnitude of changes in lCMRgl was noted from the central MCA territory to the surrounding brain regions in the ischemic hemisphere. In addition, there was a mild, but statistically significant (p less than 0.05), depression in lCMRgl with no histological damage in the non-ischemic hemisphere of the severe group.

Animals↗
PubMedDate not supplied

Effect of the ganglioside GM1, on cerebral metabolism, microcirculation, recovery kinetics of ECoG and histology, during the recovery period following focal ischemia in cats.

The effect of the ganglioside GM1 on the recovery of local cerebral glucose metabolism (lCMRgl), recovery kinetics of cerebrocortical electrical activity, cerebral blood flow and redox state as well as histological changes following focal ischemia has been studied in the cat. Ischemia was produced by occlusion of the left middle cerebral artery (MCA), and GM1 (30 mg/kg) was injected intravenously at 30 min after the MCA occlusion or at the time of release of the occlusion, at 120 min. Another group of animals were subjected to the same ischemic insult, but without GM1 treatment, and sham-operated treated and not treated cats were also studied. The animals of both GM1-treated and non-treated stroke groups were classified into 2 groups (severe and moderate) depending on the depression of electrocortical activity in the ischemic hemisphere at 30 min of the ischemia. There was a significant increase in local cerebral blood flow in the ischemic area in the treated animals. Additionally there was a significant treatment effect on the left peripheral MCA territory for lCMRgl in the 30 min treated moderate group, (p less than .05). This group of animals showed decreased lCMRgl accompanied by less severe histological damage suggesting that GM1 may produce metabolic depression so as to maintain a normal flow-metabolism couple and prevent ischemic structural damage. The possible mechanism of metabolic depression induced by GM1 is briefly discussed.

Animals↗
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Regional cerebral blood flow in stroke: hemispheric effects of cognitive activity.

Regional cerebral blood flow (rCBF) was measured with the xenon-133 inhalation technique in 15 patients with unilateral cerebral infarction and 12 matched controls. Measurements were performed during a standard resting baseline condition and during the performance of standardized verbal analogies and spatial line orientation tasks. Resting and activated CBF were lower in patients than in controls, and there were differences in the hemispheric pattern of activated CBF. Control subjects replicated earlier findings of asymmetric increase in CBF for the cognitive tasks, whereas patients showed abnormalities in lateralized CBF changes consistent with side of infarction. These findings underscore the utility of cognitive challenges in the study of rCBF in stroke. This can lead to an experimental paradigm in clinical studies of the relation between behavioral deficits and regional brain dysfunction and may also improve the utility of CBF measurements in clinical settings.

Cerebrovascular Circulation↗
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Pyridine nucleotide redox state and blood flow of the cerebral cortex following middle cerebral artery occlusion in the cat.

Acute changes in the redox state of NADH in the cerebral cortex of cats were investigated following occlusion of the middle cerebral cortex (MCA) and were correlated with alterations of regional cerebral blood flow in the ischemic cortex determined autoradiographically. Arterial occlusion was accomplished via the transorbital approach. Cortical fluorescence and reflected light signals were recorded from the central MCA territory by means of a beam-splitting fluorometer, and a fluorescence signal corrected for alterations in intravascular hemoglobin was derived. Following arterial occlusion, there was a rapid increase in cortical NADH fluorescence, peaking within 30 to 70 seconds at 20% to 40% of full scale. This was followed by a slow linear decline in fluorescence over the next several minutes. The behavior of cortical NADH fluorescence was unaffected by replacement of the ambient air over the cortical surface with nitrogen. Mean regional blood flow values in the most ischemic gyri two to 15 minutes following arterial occlusion were 21% to 23% of the corresponding values in the opposite, nonischemic hemisphere. In individual animals, peak NADH fluorescence values following arterial occlusion correlated with the extent of blood flow reduction in the affected ischemic gyri (P less than 0.05).

Animals↗
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Heterogeneities of regional cerebral blood flow during hypoxia-ischemia in the rat.

The distribution of regional cerebral blood flow (rCBF) within the cerebral hemispheres of rats was investigated following an hypoxic-ischemic insult consisting of a 30-minute exposure to 6.5% to 7% inspired oxygen coupled with unilateral ligation of the common carotid artery and maintenance of normal blood pressure (modified Levine preparation). rCBF was estimated by means of an autoradiographic method employing 14C-antipyrine. Mean arterial PO2 values of 26.8 to 27.5 mm Hg were attained during the insult period. rCBF rose above control values in all structures of the hemisphere contralateral to carotid artery ligation. Structures of the hemisphere ipsilateral to arterial ligation exhibited rCBF values less than those of the opposite side. However, the degree to which carotid artery occlusion reduced the rCBF of a structure relative to that of the opposite hemisphere varied greatly from region to region, with the greatest decrements occurring in the lateral cerebral cortex and the caudoputamen. Previous studies in this model have shown that these regions of the hemisphere ipsilateral to carotid artery occlusion are zones of frequent histological injury. These data suggest that inhomogeneities of rCBF may in part determine the phenomenon of "selective vulnerability" of the nervous system to hypoxia-ischemia.

Animals↗
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XIII. Cerebral circulation and metabolism in stroke. Cerebral circulation and metabolism in stroke study group.

An understanding of the cerebral circulation is so fundamental to comprehension of the pathogenesis of stroke that cerebral blood flow and metabolism merit review in this series of reports. The authors recognize that the research described here is very technical in nature and may appear to have little practical application to clinical medicine. Nevertheless, these matters are basic to the development of precise methods for the measurement of regional cerebral blood flow in man which could be used to monitor the therapy of stroke with greater success than is possible at present.

Brain↗
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Transient responses of cerebral blood flow and ventilation to changes in PaCO2 in normal subjects and patients with cerebrovascular disease.

In the present study, the dynamics of the cerebral blood flow (CBF) and ventilatory response to hypercapnia was investigated in a group of patients with a cerebrovascular disease and compared to responses measured in a group of normal volunteers. There was a significant correlation between the rapidity of the transient CBF and ventilatory responses and the severity of the cerebrovascular disease. While the steady state CBF response showed no such correlation, the steady state ventilatory response was reduced in patients with severe cerebrovascular disease. Various explanations for the differences in the dynamic responses of CBF and ventilation in patients with mild or severe cerebrovascular disease compared to normal subjects are considered. Measurement of these circulatory and ventilatory responses may be sensitive means for assessing the changing statls of patients with cerebrovascular disease.

Adult↗
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Comparative effects of chloralose anesthesia and Sernylan analgesia on cerebral blood flow, CO2 responsiveness, and brain metabolism in the baboon.

A comparison was made between the effects of two different anesthetics, alpha-D-gluco-chloralose and 1-1-phenylcyclohexyl piperidine hydrochloride (Sernylan), on cerebral blood flow (CBF), brain metabolism and cerebrovascular CO2 responsiveness in primates. The experiments were carried out on immobilized and artificially ventilated baboons. Anesthesia was induced either with 100/mg/kg chloralose (i.p.) or with 1 mg/kg Sernylan (i.m.). CBF in 8 different brain regions was measured by the intra-arterial 133Xe clearance technique. The CO2 responsiveness of the cerebrovascular bed was tested by a gas mixture containing 5% CO2. Chloralose depressed total as well as regional CBF compared to the effect of Sernylan. A significant shift occurred toward lower CBF values in the grey matter while white matter flow was identical in the two groups. Brain O2 consumption was significantly higher during Sernylan analgesia (3.35 +/- 0.34 ml/100 g/min) than during chloralose anesthesia (2.42 +/- 0.22 ml/100 g/min). There were no differences in glucose uptake, lactate and pyruvate production, or in arterial and cerebral venous blood gases in the two types of anesthesia. The cerebrovascular CO2 sensitivity of the Sernylan-treated baboons was higher than that of the chloralose-anesthetized animals, in both the grey and white matter.

Animals↗
PubMedDate not supplied

Diaschisis with cerebral infarction.

Fifteen patients admitted to Philadelphia General Hospital with acute strokes had repeated measurements of cerebral blood flow measured by the 133Xenon inhalation method. A progressive decline in cerebral blood flow in both hemispheres was observed during the first week after infarction in twelve of these patients. This decline could be partially explained by loss of autoregulation, but could not be correlated with level of consciousness, clinical status of PCO2. This progressive decline in flow in the non-ischemic hemisphere indicates a process more complex than a simple destruction of axonal afferants to neurons as implied by the term diaschisis. The flow changes in the non-ischemic hemisphere are likely caused by a combination of the immediate effects of decreased neuronal stimulation modified by loss of autoregulation, release of vasoactive substances, cerebral edema, and other factors.

Aged↗