Relationship between the cortical evoked potential and local cortical blood flow following acute middle cerebral artery occlusion in the baboon

In most experimental studies of the effects of ischemia on CNS electrical activity, the ischemia produced has been total. The present experiments, however, were designed to establish quantitatively the changes in electrical activity corresponding to different degrees of cerebral ischemia. The somatosensory evoked potential was measured at various sites on the exposed postcentral gyrus of the anesthetized baboon, and cortical blood flow was assessed in the region of the evoked potential electrode by the highly focal method of hydrogen clearance. The technique of middle cerebral artery occlusion was used to reduce blood flow over the hemisphere. Following occlusion of the artery, the amplitude of the evoked potential typically diminished steadily at a rate depending on the level of residual local blood flow. The rate of depression of the evoked potential amplitude (expressed in units of percent of control per minute) was highly and significantly correlated with the residual flow (r = ?0.95, P < 0.001), which indicated a linear relationship between these variables, the regression line intercepting the flow axis at 15.2 ml/100g/min. The data also strongly suggested a threshold-type relationship between the amplitude of the evoked potential and the local blood flow: If the flow was greater than about 16 ml/100g/min the evoked potential was not affected, but at flows less than about 12 ml/100g/min the evoked potential was abolished.     

Cerebral blood flows and tissue oxygen levels associated with maintenance of the somatosensory evoked potential and cortical neuronal activity in focal ischemia

The middle cerebral artery was occluded in 18 cats to evaluate the physiological consequences of cerebral blood flow reductions on the somatosensory evoked potential, spontaneous neuronal activity, and oxygen availability in the ipsilateral and contralateral hemispheres. In the ipsilateral ectosylvian gyrus high-grade ischemia was produced as blood flow in the gray matter was reduced from 52.1 +/- 8.6 (mean +/- SE) to 13.3 +/- 9.0 ml/100 g/min and in the white matter from 33.8 +/- 5.6 to 6.1 +/- 6.4 ml/100 g/min. This significant reduction (p less than 0.05) was associated with abolition of the cortical component of the somatosensory evoked potentials. In all animals occlusion resulted in a predictable extended latency change and a variable amplitude response of the cortical component of the contralaterally recorded somatosensory evoked potentials. In 5 animals, oxygen availability was measured and spontaneous neuronal activity in the contralateral hemisphere was recorded. Volume expansion and hemodilution with either dextran or saline infusions elevated cerebral blood flow in the contralateral gray matter significantly (p less than 0.05) compared with the control and clip values. Ipsilateral spontaneous activity stopped within 4-12 minutes of occlusion, while contralateral spike activity persisted at rates at least equal to those recorded immediately following occlusion.     

Anesthetic modulation of cerebral hemodynamic and evoked responses to transient middle cerebral artery occlusion in cats

We measured cerebral blood flow and somatosensory evoked potentials during transient focal cerebral ischemia in cats to compare the effects of four commonly used anesthetic regimens: ketamine/fentanyl/N2O (fentanyl), pentobarbital, ketamine/alpha-chloralose (alpha-chloralose), and ketamine/halothane/N2O (halothane). Six cats in each group were subjected to 60 minutes of left middle cerebral artery occlusion followed by 120 minutes of reperfusion. Although the amplitude of the initial somatosensory evoked potential wave complex was highest in the alpha-chloralose group (58.6 +/- 16.5 microV) and smallest in the halothane group (27.5 +/- 5.7 microV), amplitude fell by 75% in all groups upon occlusion. Baseline cerebral blood flow varied substantially between groups (e.g., in the right intersylvian gyrus: fentanyl, 96 +/- 12; pentobarbital, 30 +/- 5; alpha-chloralose, 24 +/- 3; and halothane, 76 +/- 11 ml/min/100 g). Occlusion decreased cerebral blood flow to subcortical (e.g., left caudate) structures in all groups (fentanyl, 29 +/- 11%; pentobabital, 45 +/- 12%; alpha-chloralose, 27 +/- 13%; and halothane, 18 +/- 5% of baseline). Postischemic hyperemia occurred in the cortical regions of cats anesthetized with pentobarbital or alpha-chloralose that had reduced cerebral blood flows during occlusion but not in cats anesthetized with fentanyl (cerebral blood flow during occlusion not different from that of cats anesthetized with pentobarbital or alpha-chloralose) or halothane. After 120 minutes of reperfusion, cerebral blood flow had returned to baseline values in all groups. Recovery of cerebral blood flow and somatosensory evoked potential amplitude at that time did not differ among groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low CBF, discontinuous EEG activity, and periventricular brain injury in ill, preterm neonates

Cerebral blood flow was measured by intravenous 133Xe clearance one to four times during the first 48 h of life in 20 infants, born after 27 to 33 weeks of gestation, who were under mechanical ventilation and being monitored by amplitude integrated EEG, resulting in 36 sets of simultaneous CBF and EEG measurements. Mean CBF infinity, a measure of global flow to white as well as grey matter, was 10.0 ml/100 g/min +/- 3.5 SD. Definite EEG activity was seen with CBF infinity values as low as 5 ml/100 g/min. CBF infinity was related to the level of EEG activity, discontinuous EEG activity being associated with low CBF infinity (p = 0.014). It was not possible to determine if this relation indicated the presence of marginal ischaemia or primary inhibition of electrical activity resulting in decreased CBF, two infants developing periventricular leucomalacia, however, and one who developed intraparenchymatous hemorrhage were among the seven with CBF infinity values of less than or equal to 8 ml/100 g/min (p = 0.031). This suggests that ischaemia of periventricular white matter may have been present concurrently with cortical electrical activity.     

Tirilazad mesylate does not improve early cerebral metabolic recovery following compression ischemia in dogs.

BACKGROUND AND PURPOSE: Tirilazad mesylate (U74006F) has been reported to improve recovery following cerebral ischemia. We conducted a randomized blinded study to determine if the drug would improve immediate metabolic recovery after complete cerebral compression ischemia. METHODS: Mongrel dogs were anesthetized with pentobarbital and fentanyl and treated with either vehicle (citrate buffer, n = 8) or tirilazad (1.5 mg/kg i.v. plus 0.18 mg/kg/hr, n = 8). Normothermic complete cerebral compression ischemia was produced for 12 minutes by lateral ventricular fluid infusion to raise intracranial pressure above systolic arterial pressure. Cerebral high-energy phosphate concentrations and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Cerebral blood flow was measured with radiolabeled microspheres, and oxygen consumption was calculated from sagittal sinus blood samples. Somatosensory evoked potentials were measured throughout the experiment. RESULTS: During ischemia, both groups demonstrated complete loss of high-energy phosphates and a fall in intracellular pH (vehicle, 5.76 +/- 0.23; tirilazad, 5.79 +/- 0.26; mean +/- SEM). At 180 minutes of reperfusion, there were no differences between groups in recovery of intracellular pH (vehicle, 6.89 +/- 0.07; tirilazad, 6.88 +/- 0.18), phosphocreatine concentration (vehicle, 89 +/- 16%; tirilazad, 94 +/- 24% of baseline value), oxygen consumption (vehicle, 2.6 +/- 0.2 ml/min/100 g; tirilazad, 1.8 +/- 0.5 ml/min/100 g), or somatosensory evoked potential amplitude (vehicle, 11 +/- 6%; tirilazad, 7 +/- 4% of baseline value). Forebrain blood flow fell below baseline levels at 180 minutes of reperfusion in the tirilazad-treated animals but not in the vehicle-treated dogs (vehicle, 28 +/- 4 ml/min/100 g; tirilazad, 18 +/- 5 ml/min/100 g). CONCLUSIONS: We conclude that tirilazad pretreatment does not improve immediate metabolic recovery 3 hours following 12 minutes of normothermic complete ischemia produced by cerebral compression.     

Age-related differences in recovery of blood flow and metabolism after cerebral ischemia in swine

We tested two hypotheses: 1) that cerebral blood flow, oxygen consumption, and evoked potentials recover to preischemic values at 120 minutes of reperfusion more completely in 1-2-week-old piglets than in 6-10-month-old pigs after complete ischemia; and 2) that recovery of cerebral blood flow, oxygen consumption, and electrical function in piglets and pigs at 120 minutes of reperfusion is better after incomplete than after complete ischemia. During 30 minutes of ischemia produced by intracranial pressure elevation, cerebral blood flow determined by the microspheres technique was decreased to 0-1 ml/min/100 g with complete ischemia, to 1-10 ml/min/100 g with severe incomplete ischemia, or to 10-20 ml/min/100 g with moderate incomplete ischemia. During reperfusion after complete ischemia, both piglets and pigs demonstrated hyperemia but delayed hypoperfusion occurred in more brain regions in pigs, oxygen consumption returned to preischemic values in piglets but not in pigs (70 +/- 10% of preischemic values), and evoked potentials recovered better in piglets than in pigs (24 +/- 4% and 9 +/- 4% of preischemic values, respectively). Both piglets and pigs had fewer brain areas with hyperemia and hypoperfusion and improved oxygen consumption and electrical function during recovery from incomplete than from complete ischemia. We speculate that piglets tolerate complete ischemia better than pigs because of decreased reperfusion injury and that both groups recover better from incomplete than complete ischemia because of improved substrate supply during ischemia.     

Conjugated superoxide dismutase reduces extent of caudate injury after transient focal ischemia in cats.

We tested the efficacy of preischemic and postischemic systemic treatment with 30,000 units polyethylene glycol-conjugated superoxide dismutase in a reperfusion model of focal cerebral ischemia. Forty-one anesthetized cats underwent 2 hours' occlusion of the left middle cerebral artery and both common carotid arteries followed by 4 hours of reperfusion. Cats were blindly assigned to one of three groups: treatment with vehicle (10% polyethylene glycol in saline, n = 17), pretreatment with drug 3 hours before ischemia (n = 12), and posttreatment with drug at the time of reperfusion (n = 12). Size of the ischemic injury was calculated from 2,3,5-triphenyltetrazolium chloride staining. Injury in the caudate nucleus was significantly reduced with pretreatment (28 +/- 6% of ipsilateral caudate volume, mean +/- SEM) compared with the vehicle (56 +/- 8%). Posttreatment did not significantly ameliorate caudate injury (46 +/- 10%). Between the first and second hours of ischemia ipsilateral caudate blood flow determined using microspheres increased significantly from 11 +/- 4 to 16 +/- 5 ml/min/100 g with pretreatment, but blood flow remained constant throughout ischemia with vehicle (8 +/- 2 ml/min/100 g) and posttreatment (10 +/- 3 ml/min/100 g). The size of cortical injury (vehicle, 17 +/- 5%; pretreatment, 11 +/- 3%; posttreatment, 17 +/- 5% of hemispheric volume) did not differ significantly among groups. Somatosensory evoked potential recovery did not differ among groups. We conclude that pretreatment with conjugated superoxide dismutase can ameliorate the extent of injury in an end-artery region, such as the caudate nucleus, in a reperfusion model of focal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic brain ischemia in the monkey assessed by somatosensory evoked potentials and local blood flow measurements

Physiological changes occurring in experimentally induced chronic ischemic areas of the brain in monkeys have been investigated by measuring local cerebral blood flow (lCBF) and recording somatosensory evoked potentials (SEPs) to median nerve stimulation in the cortex and thalamus (VPL). Ischemia was produced by occlusion of the middle cerebral artery (MCA). Its development was followed for weeks in the unanesthetized monkey. SEPs in VPL and cortex were shown to be useful indicators of neuronal activity in the course of brain ischemia. The most reliable parameters were found to be the amplitude of components P10, P12 and P20 of the cortical SEP, generated around the central sulcus. The relationship between the changes in spontaneous recovery of the SEPs, lCBF and behavioral signs, in the course of time, revealed characteristic patterns. Different components of the cortical SEP provide useful information on the localization of the ischemic cortical area. In addition, the amplitude of the VPL SEP may also change significantly after the occlusion of the MCA. Clear evidence for the phenomenon of diaschisis in terms of SEPs, was found in only one animal. An analysis of the relationship between lCBF and the amplitude of the SEPs showed that cortical SEPs could be measured at local CBF levels as low as 15 ml/100 g X min. The relationship between lCBF and cortical SEP amplitude was approximately linear in the range from about 60 ml/100 g X min down to 15 ml/100 g X min.     

Electrical stimulation of motor cortex in experimental cortical ischaemia: pyramidal responses at C5 and the surface EMG.

In 7 baboons maintained under propofol anaesthesia, pyramidal tract responses were related to the corresponding peripheral EMG evoked by electrical stimulation of the motor cortex under conditions of focal cortical ischaemia. Pyramidal responses were recorded epidurally at the C5 level and the EMG was recorded from the contralateral hand or foot muscle using subdermal needle electrodes. Cortical ischaemia was produced by transorbital occlusion of the common anterior cerebral artery, and regional cortical blood flow was measured by the hydrogen clearance method. In the normally perfused brain, the later I waves of the C5 response required a lower stimulus strength to elicit them than the earlier I1 wave. It was more difficult to record the EMG from the hand than from the foot following stimulation of the corresponding cortex even though the C5 responses were always obtained in both cases. With moderate ischaemia, the later I waves were selectively abolished, leaving the D and I1 waves. EMG amplitude was significantly correlated with cortical blood flow (r = 0.88, P less than 0.005), and the threshold of cortical flow for the EMG was 10-13 ml/100 g/min. Our results indicate that changes in amplitude of the late I waves and particularly of the EMG are sensitive indicators of cortical ischaemia.     

Comparison of the effects of ischaemia on early components of the somatosensory evoked potential in brainstem, thalamus, and cerebral cortex

In 14 ventilated, normocapnic baboons anaesthetised with alpha-chloralose, local CBF (hydrogen clearance) and the amplitude and latency of local components of the somatosensory evoked potential (SEP, median nerve stimulation) were measured bilaterally in ventrobasal thalamus (VPL), medial lemniscus (ML), and cerebral cortex before and during progressive ischaemia, produced by occlusion of the right middle cerebral artery and subsequent controlled reductions in mean systemic blood pressure (MSBP). The first significant reduction from control of the left cortical SEP amplitude occurred in the range of 30-40 mm Hg MSBP, but those of the VPL and ML responses only below 30 mm Hg; in the range of 20-30 mm Hg, the average SEP amplitudes in cortex, VPL, and ML were 8.6, 72.6, and 90.7% of control, respectively. In terms of local CBF, the cortical SEP threshold was in the range of 15-20 ml/100 g/min (as in previous work), that of VPL in the range of 10-15 ml/100 g/min, but the ML response was only markedly reduced below 10 ml/100 g/min. Thus, the differential ischaemic sensitivity of the SEP between the three regions was clearly demonstrated. These results indicate that as one descends the neuraxis, there is an increasing resistance of electrophysiological function to systemic hypotension, together with a decreasing threshold for local ischaemia.     

In vivo studies on intracellular pH, focal flow, and vessel diameter in the cat cerebral cortex: effects of altered CO2 and electrical stimulation

The time course of changes in cortical tissue pH (pHi) and blood flow during cortical seizures in halothane-anesthetized cats was examined. The clearance of the molecular form of umbelliferone (Um) was used to estimate focal cortical blood flow (CBFu), whereas the ratio of the molecular to the ionic form of the molecule was used to concurrently calculate the local pHi. Resting pHi and flow in normocarbic animals was 7.116 +/- 0.008 and 46 +/- 8 ml/100 g/min, respectively. Respiratory induced alterations of PaCO2 over a range of 20-60 torr revealed a correlated change in pHi from 7.39 +/- 0.05 to 7.01 +/- 0.03 and a monotonic increase in the rate of Um clearance (slope 0.89 +/- 0.13 ml/100 g/min/torr). Focal electrical stimulation of the cortex resulted in a rapid vasodilation (50% dilation = 1-3 s) of pial arterioles and venules and an increase in Um clearance. pHi showed no significant change until around 10 s. The maximum fall in pHi occurred by 30-60 s (6.85 +/- 0.054). Longer intervals of stimulation (10 min) resulted in no further decline in pHi, but upon cessation of stimulation. pHi remained acidotic for poststimulation periods up to 10 min, with a mild but statistically significant acidosis being observed at 20 min. The absolute decline in pH observed following stimulation appeared to be closely regulated, as comparable levels following stimulation were observed during hypocarbia and hypercarbia. These observations thus suggest that pHi regulation during intense cortical activation may be considered in three phases: following the onset of activity, an initial acute regulation of pHi at control levels; an intracellular acidosis of around 6.8, which is closely regulated and which can be readily reversed upon termination of stimulation; and during continued stimulation, a change in state where in spite of no further change in pHi, the ability of the cortex to return to control pHi appears to be significantly impaired.     

Kinetics of resolution of transient increases in extracellular potassium activity: relationships to regional blood flow in primate cerebral cortex

Previous studies have established that in cerebral cortex subjected to progressive reduction in blood flow, two distinct thresholds of flow may be identified below which cellular function is impaired: the cortical evoked response loses amplitude when local flow falls below 18ml/100gm/min, and below 11ml/100gm/min a major increase in extracellular K+ activity (Ke) occurs. However, further evidence suggests that even at higher flows the capacity of the tissue to handle induced ionic changes may be impaired. To investigate this point, we studied the kinetics of resolution of Ke following a transient increase produced by local electrical stimulation, in relation to the local pre-stimulus flow (reduced by acute middle cerebral artery occlusion) in baboons. Flow was measured by the hydrogen clearance method and Ke by ion-exchanger micro-electrodes, in the same cortical regions. In primary induced transients (those increases in Ke elicited by cortical stimulation, and reported previously,) Ke attained a maximum value of 8-10 mM and then decayed towards the 4-mM baseline. The half-time of this decay was significantly increased from normal in the flow range 20-40 ml/100 gm/min, and increased further at lower flows until, below 11ml/100gm/min, Ke clearance was undetectable. Thus, cortical ion homeostasis appeared impaired at flows substantially closer to normal than those thresholds mentioned above, a result discussed in terms of impairment of active Ke clearance mechanisms. Secondary induced transients arose during a primary induced transient, reaching considerably higher peak values (8-30 mM) of Ke (indicating temporary clearance loss) and with slower decay rate than the primary. Spontaneous transients, not associated with any stimulus, were also observed; like secondary transients, they occurred only at flows below 20ml/100gm/min and showed a reduction in clearance rate with progressive ischemia. They resemble spreading depression and their generation is discussed in terms of the ionic and metabolic conditions at their time of origin.     

Polyamine inhibition preserves somatosensory evoked potential activity after transient cerebral ischaemia

We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is related to deficits in electrocortical function as measured by somatosensory evoked potential (SEP). Adult Mongolian gerbils were anaesthetized with ketamine and prepared for monitoring SEP, cerebral blood flow (CBF) in parietal and frontal regions by H2 clearance, and for bilateral carotid artery occlusion (BCO). Seven animals served as controls and received saline. Another 7 animals were treated with the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO) (100 mg/kg I.P.) just prior to 40 min BCO followed by 4 h reperfusion. With BCO, both CBF and SEP declined significantly. In control animals, CBF fell from basal 37.8 +/- 4.7 cc/100 g/min to 2.9 +/- 1.2 cc/100 g/min and recovered to 22.7 +/- 3.5 cc/100 g/h over the 4 h reperfusion period. DFMO treatment did not alter this CBF pattern. SEP amplitude declined to 11.3 +/- 3.2% basal during occlusion. DFMO preserved SEP during ischaemia (35.5 +/- 16.8% basal) and remained significantly more preserved during reperfusion (p less than 0.05). These results suggest that polyamines are involved in the progressive decline in neuroelectrical function which occurs during occlusion/reperfusion in the Mongolian gerbil. The observation that polyamine inhibition preserves electrical function despite not altering blood flow indicates that the effects of polyamines are not manifested at the level of the vasculature but perhaps at the neuronal membrane.     

The effects of calcium antagonism on the epicerebral circulation in early vasospasm

We have studied the effects of the calcium antagonist verapamil on the epicerebral arteriovenous transit time and regional epicerebral circulation of dogs by direct measurement of arterial diameters, fluorescein angiography, and krypton-85 regional epicerebral blood flow analysis. A large craniectomy was performed and vasoconstriction was induced by the subarachnoid injection of human platelet-rich plasma (PRP) pretreated with 25 mu M of ADP to cause maximum aggregation. Once vasoconstriction was established, verapamil (0.1 mg/kg) was topically applied to the perforated arachnoid. The PRP-ADP produced a mean decrease in the arterial diameters of 38.2 +/- 1.6% (p less than 0.01) at 10 minutes after its injection and verapamil produced a mean dilatation of 19.5 +/- 2.5% (p less than 0.01), compared to control values. Regional epicerebral blood flow was 54.9 +/- 3.4 ml/100 g/min in the control state, 34.8 +/- 3.2 ml/100 g/min (p less than 0.01) during vasospasm, and 78.2 +/- 4.5 ml/100 g/min (p less than 0.01) after verapamil. Fluorescein angiography, after verapamil, demonstrated a mean acceleration of the arteriovenous circulation time of 4.5 +/- 0.8 seconds (p less than 0.01) compared to the spasm value. We concluded that the topical application of verapamil can dilate previously constricted cortical arteries and that this dilatation is associated with acceleration of the epicerebral transit time and increased cerebral blood flow.     

Extracellular potassium activity, evoked potential and tissue blood flow. Relationships during progressive ischaemia in baboon cerebral cortex.

Extracellular K+ activity (Ke), local tissue blood flow and the cortical evoked potential (EP) were measured concurrently in the cerebral cortex of baboons anaesthetised with a-chloralose. Flows were progressively reduced from normal by occlusion of the middle cerebral artery and controlled steps of exsanguination. Our data suggest that 3 stages may be identified in the disturbance of K+ homeostasis produced by progressive ischaemia. In the first stage, at flow levels similar to those sufficient to abolish the EP (12-16 ml/100 g/min), small, self-limiting increases in Ke occur, probably reflecting K+ efflux into the extracellular space (ECS) with partial impairment of K+ clearance from the ECS. The second stage occurs at distinctly lower (P less than 0.01) levels of flow (8-11 ml/100 g/min), and is characterized by a massive (30-80 mM) increase in Ke, which we attribute to an increase in ionic permeability of cell membranes with further impairment or overloading of K+ clearance mechanisms. In the third stage, at flows below about 6-8 ml/100 g/min, the data indicate an inverse relationship between flow and Ke with persisting high Ke levels, suggesting complete loss of K+ clearance. Transient increases of Ke also occur in the flow range 4-13 ml/100 g/min, the rate of recovery of Ke in their decay phase being positively corelated with flow (P less than 0.005).     

Cerebral circulation dynamics following fasudil intravenous infusion: a CT perfusion study]

Using CT perfusion studies we evaluated changes in the cerebral circulation before and after the intravenous administration of fasudil 60 mg in 8 patients 7 to 14 days after a subarachnoid hemorrhage. The mean duration to the peak of the time-density curve and the average peak value did not change. In areas with cerebral blood perfusion (CBP) less than 40 ml/100 g/min, the CBP increased from 34.4 +/- 4.7 ml/100 g/min to 41.0 +/- 8.2 ml/100 g/min (p < 0.01) after fasudil infusion, the cerebral blood volume (CBV) rose from 2.41 +/- 0.53 ml/100 g to 2.55 +/- 0.5 ml/100 g (p < 0.05), and the mean transit time (MTT) decreased from 5.09 +/- 1.13 s to 4.82 +/- 0.89 s (p < 0.05). In areas where the CBP was more than 41 ml/100 g/min, the CBP did not change (from 51.8 +/- 7.6 ml/100 g/min to 50.4 +/- 8.4 ml/100 g/min), the CBV decreased (from 2.75 +/- 0.62 ml/100 g to 2.67 +/- 0.55 ml/100 g, p < 0.05), and the MTT did not change (from 3.80 +/- 0.76 s to 3.77 +/- 0.72 s). These results suggest that intravenous infusion of fasudil 60 mg increases cerebral blood flow and cerebral blood volume and shortens MTT in areas with decreased blood flow due to vasospasm.     

Measurement of blood flow to the adrenal capsule, cortex and medulla in dogs after hemorrhage by fluorescent microspheres

Changes in adrenal medullary and total cortical blood flow after hemorrhage have been described using radioactive microspheres. To assess changes in adrenal capsular and in intracortical adrenal blood flow, a method was used based on microscopic detection of non-radioactive microspheres. Injection of microspheres labelled with fluorescent dyes permitted multiple determinations of blood flow. Pentobarbital anesthetized dogs (n = 6) were prepared acutely with left ventricular and aortic catheters for injection and collection of microspheres, respectively. Adrenal denervation was done unilaterally by cutting the thoracic splanchnic nerve. Injections of 16-microns spheres were made prior to and immediately after 18 ml/kg hemorrhage done over 6 min. Dogs were killed with KCl and adrenals were removed, fixed and sectioned at 80 microns. Using fluorescence microscopy, microspheres were counted in the adrenal capsule, zona glomerulosa, inner cortex (zona facsiculata and reticularis), and the medulla. The majority (95%) of microspheres in the adrenal cortex were trapped in the zona glomerulosa, precluding an independent estimate of blood flow to the inner cortex. Thus, total cortical blood flow was determined by summing the number of 16-microns microspheres in the zona glomerulosa and inner cortex. Prior to hemorrhage, blood flow was greater in the capsule (5.4 +/- 1.6 ml/min/g) compared to the cortex (1.8 +/- 0.9 ml/min/g) and the medulla (2.9 +/- 1.8 ml/min/g). Splanchnicotomy did not change blood flow in the resting state. Following hemorrhage, in innervated glands, medullary blood flow increased to 8.6 +/- 3.1 ml/min/g, whereas blood flow to other zones was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spinal cord blood flow measured by a hydrogen clearance technique.

Spinal cord blood flow (SCBF) has been measured in segments of the thoracolumbar cord of dogs using the hydrogen clearance technique. Clearances were recorded and flows calculated from electrodes placed in grey and white matter. The position of the recording electrodes was marked by diathermy and confirmed in each experiment. The SCBF in the white matter for 82 clearances was 13.7+/-4.5 ml/100 g/min using pentobarbitone anaesthesia. In the grey matter both monoexponential and biexponential clearances were recorded from electrodes placed in grey matter. There was no difference in flows calculated from the monoexponentail and slow components. SCBF from the slow components or monoexponentials was 12.0+/-4.5 ml/100g/min. The flow from the fast component was 69+/-11 ml/100 g/min. with pentobarbitone anaesthesia and 97.5+/-32.9 ml/100g/min with alpha-chloralopse anaesthesia. The flow calculated from the fast component did not correlate to changes of PaCO2. The slow component of any biexponential clearances was used to calculate flows from electrodes placed in the grey matter. There was no significant difference between flows from the grey matter (calculated from the slow component) and the white matter. Simultaneously recorded cortical and sub-cortical -lows were higher than in spinal grey and white matter. There was considerable variation in flow from animal to animal. The area of spinal grey matter is small and surrounded by white matter and the flow recorded from electrodes placed in grey matter is probably the average SCBF representing a mixture of grey and white flow. This will arise because of the rapid diffusibility of hydrogen gas between the tissues. It is therefore difficult to ascribe the flow from a centrally placed cord electrode to a definite anatomical compartment.     

Effect of preischemia cyclooxygenase inhibition by zomepirac sodium on reflow, cerebral autoregulation, and EEG recovery in the cat after global ischemia

Zomepirac sodium (ZS) (5 mg/kg i.v.) was used to evaluate the effects of preischemia cyclooxygenase inhibition on CBF (as assessed by 133Xe clearance), CBF-PaCO2 responsiveness, and electrophysiologic (EEG) parameters before and after a 15-min period of complete global ischemia produced by four-vessel occlusion and mild hypotension. During the 15-min period of ischemia, CBF was essentially zero. Following reflow all groups displayed an initial hyperemia as compared with control (92 +/- 11 vs. 141-146 ml/100 g/min). Saline-treated animals during reflow displayed a delayed hypoperfusion (26 +/- 3 ml/100 g/min), which showed no improvement during the 2-h reflow period prior to death. In contrast, ZS-treated animals during reflow displayed significantly higher flows during the hypoperfusion phase (72 +/- 9 ml/100 g/min). The CBF-PaCO2 response displayed an approximately sevenfold reduction in slope at 2 h after reflow in saline-treated animals. This decrease in PaCO2 reactivity was not observed in the ZS-pretreated animals. With regard to EEG, all animals showed a total flattening during the 15 min of ischemia. In saline-treated animals only one of seven showed any sign of even marginal recovery. In ZS-treated animals EEG activity showed prominent recovery in seven of seven. Brainstem auditory evoked potentials were monitored and showed prominent recovery of amplitude and latency in ZS but not saline-treated animals during reflow.     

Extended latency of the cortical component of the somatosensory-evoked potential accompanying moderate increases in cerebral blood flow during systemic hypoxia in cats

In 24 adult cats, the somatosensory-evoked potential (SEP) and cerebral blood flow (CBF) were measured under paralyzed, anesthetized conditions during exposure to two different ventilatory regimens. Group I cats (ventilated from 20 to 2% oxygen) responded with a significant increase in white matter blood flow from 25.0 +/- 7.8 to 43.8 +/- 10.5 ml/100 g/min recorded at 7% O2. Gray matter blood flows in these animals increased but not to significant levels above the control blood flow measured at 20%. No significant changes in blood flow were observed in group II animals ventilated over the range of 25-3% oxygen as gray matter rose slightly (but not significantly) with hypoxia and white matter flows remained at levels of 25-30 ml/100 g/min. The latency of the cortical component of the SEP was related to the degree of hypoxia. For both groups, significant extensions in the latency to the occurrence of the cortical component of the SEP (normalized to the % of control SEP) occurred in each case (P less than 0.05). An inverse, linear relationship existed between the latency to the appearance of cortical component (ms) and the percentage oxygen concentration of the ventilatory mixture. No significant changes in thalamocortical conduction times were found, which indicates that hypoxia may have generalized effects on the synaptic pathways supporting the conduction of the SEP. The variation in blood flow and the latency of the cortical component observed between groups I and II may reflect the oxygen concentration used at the beginning of the experiment (25 vs 20%) and the gradations between them vs 3 and 2%.(ABSTRACT TRUNCATED AT 250 WORDS)