Effects of nalmefene, CG3703, tirilazad, or dopamine on cerebral blood flow, oxygen delivery, and electroencephalographic activity after traumatic brain injury and hemorrhage

Hemorrhage after traumatic brain injury (TBI) in cats produces significant decreases in cerebral oxygen delivery (DcereO2) and electroencephalographic (EEG) activity. To determine whether effective treatments for the separate insults of TBI and hemorrhagic shock would also prove effective after the clinically relevant combination of the two, we measured the effects of a kappa-opiate antagonist (nalmefene), an inhibitor of lipid peroxidation (tirilazad), a thyrotropin-releasing hormone analog (CG3703), a clinically useful pressor agent (dopamine) or a saline placebo on cerebral blood flow (CBF), and EEG activity after TBI and mild hemorrhagic hypotension. Cats (n = 40, 8 per group) were anesthetized with 1.6% isoflurane in N2O:O2 (70:30) and prepared for fluid-percussion TBI and microsphere measurements of CBF. Cats were randomized to receive nalmefene (1 mg/kg), tirilazad (5 mg/kg), CG3703 (2 mg/kg), dopamine (20 microg x kg(-1) x min[-1]) or a saline placebo (2 ml, 0.9% NaCl). Animals were injured (2.2 atm), hemorrhaged to 70% of preinjury blood volume, treated as just described and resuscitated with a volume of 10% hydroxyethyl starch equal to shed blood. CBF was determined and EEG activity recorded before injury, after hemorrhage, and 0, 60, and 120 min after resuscitation (R0, R60, and R120). CBF increased significantly after resuscitation (R0) in the nalmefene- and CG3703-treated groups. CBF did not differ significantly from baseline in any group at R60 or R120. DcereO2 was significantly less than baseline in the saline-, dopamine-, and tirilazad-treated groups at R60 and in the dopamine-, tirilazad-, and CG3703-treated groups at R120. EEG activity remained unchanged in the nalmefene-treated group but deteriorated significantly at R60 or R120 compared to baseline in the other groups. Nalmefene and CG3703 preserved the hyperemic response to hemodilution (otherwise antagonized by TBI), and nalmefene prevented the deterioration in DcereO2 and EEG activity that occurs after TBI and hemorrhage.     

Vasoreactive effect of acetazolamide as a function of time with sequential PET 15O-water measurement

The accurate assessment of vascular flow reserve is crucial for the evaluation of risk among patients with cerebrovascular disease. In six patients with unilateral occlusion of the internal carotid artery and one patient with unilateral occlusion of the middle cerebral artery (mean +/- S.D. age = 68 +/- 3 years), we measured cerebral blood flow (CBF) after the administration of 940 MBq 15O-water using a remotely controlled power injector. Studies were performed at rest, after 10 min, and then 10, 20 and 30 min after the administration of 1 mg acetazolamide to evaluate the vasoreactive effect, as reflected by an increase in CBF. Sixteen regions of interest (ROIs) were drawn over the CBF images. These ROIs were as follows in each hemisphere: Area I, four areas in the cortical middle cerebral arterial territory (superior frontal, frontal, temporal and parietal areas); Area II, four areas of the deep middle cerebral and vertebral arterial territory (occipital area, basal ganglia, thalamus and cerebellum). Taking normalized resting CBF to be 100%, the mean CBF measured 10, 20 and 30 min post-injection using sequential positron emission tomography was as follows: Area I, 141.4 +/- 16.3, 127.7 +/- 15.3 and 128.2 +/- 17.4% for non-occluded sites and 116.3 +/- 22.8, 112.7 +/- 16.4 and 114.9 +/- 17.1% for occluded sites; Area II, 143.4 +/- 14.5, 126.2 +/- 10.4 and 125.0 +/- 12.9% for non-occluded sites and 141.9 +/- 28.9, 126.0 +/- 20.5 and 124.1 +/- 17.1% for occluded sites. A significant difference in mean CBF was noted between the non-occluded and occluded sites in Area I, the most marked difference of 25.1% being observed 10 min after the administration of the acetazolamide. We conclude that for an accurate assessment of vascular reserve in patients with cerebrovascular disease, CBF should be measured 10 min post-administration of the acetazolamide.     

Effect of dehydroepiandrosterone sulfate on fetal middle cerebral artery flow velocity waveforms in term pregnancy

OBJECTIVE: To investigate whether bolus injection of dehydroepiandrosterone sulfate (DHAS) is associated with changes in fetal middle cerebral artery flow velocity waveforms in term pregnancy. METHODS: Ten normal full-term pregnant women received the administration of a 200-mg intravenous dose of DHAS in 20 ml of 5% dextrose. Ten normal full term pregnant women received 20 ml 5% dextrose as controls. Color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were made on fetuses in each group before and 10 min, 30 min, 60 min, 90 min. and 120 min after DHAS or dextrose administration. The pulsatility index (PI) values for the middle cerebral artery, and umbilical artery, and fetal heart rate were recorded. RESULTS: In the DHAS group, middle cerebral artery PI decreased from baseline by 24% (p<.05) after 10 min, and the mean reduction was 22% (p<.05) after 30 min. The PI returned to the baseline value 60 min later. In the control group, there was no change in middle cerebral artery PI. No change was found in umbilical artery PI or fetal heart rate in the control or DHAS group. CONCLUSION: DHAS induces a significant decrease in the fetal middle cerebral artery PI, which suggests a possible decrease in fetal cerebral vascular impedance in term pregnancy.     

Somatostatin-14 modulates acid-dependent inhibition of meal-stimulated gastrin via muscarinic pathways in dogs

There is no general agreement regarding several aspects of the role of the sympathetic system on cerebral haemodynamics such as extent of effectiveness, operational range and site of action. This study was planned to identify the effect of a generalised sympathetic activation on the cerebral haemodynamics in healthy humans before it is masked by secondary corrections, metabolic or myogenic in nature. A total of 35 healthy volunteers aged 20-35 underwent a 5 min lasting cold pressor test (CPT) performed on their left hand. The cerebral blood flow (CBF) velocity in the middle cerebral arteries and arterial blood pressure were recorded with transcranial Doppler sonography and with a non-invasive finger-cuff method, respectively. The ratio of arterial blood pressure to mean blood velocity (ABP/Vm) and Pulsatility Index (PI) were calculated throughout each trial. CPT induced an increase in mean ABP (range 2-54 mmHg depending on the subject) and only a slight, though significant, increase in blood velocity in the middle cerebral artery (+2.4 and +4.4% on ipsi- and contralateral side, respectively). During CPT, the ratio ABP/Vm increased and PI decreased in all subjects on both sides. These changes began simultaneously with the increase in blood pressure. The increase in ABP/Vm ratio is attributed to an increase in the cerebrovascular resistance, while the concomitant reduction in PI is interpreted as due to the reduction in the compliance of the middle cerebral artery. The results suggest that generalised increases in the sympathetic discharge, causing increases in ABP, can prevent concomitant increases in CBF by acting on both small resistance and large compliant vessels. This effect is also present when a slight increase in blood pressure occurs, which suggests a moderate increase in the sympathetic discharge, i.e. when ABP remains far below the upper limit of CBF autoregulation.     

Effects of cisatracurium on cerebral and cardiovascular hemodynamics in patients with severe brain injury

BACKGROUND: For neuroanesthesia and neurocritical care the use of drugs that do not increase or preferentially decrease intracranial pressure (ICP) or change cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) are preferred. The current study investigates the effects of a single rapid bolus dose of cisatracurium on cerebral blood flow velocity, ICP, CPP, mean arterial pressure (MAP) and heart rate (HR) in 24 mechanically ventilated patients with intracranial hypertension after severe brain trauma (Glasgow coma scale <6) under continuous sedation with sufentanil and midazolam. METHODS: Patients were randomly assigned to receive either 2xED95 (n=12) or 4xED95 (n=12) of cisatracurium as a rapid i.v. bolus injection. Before and after bolus administration mean cerebral blood flow velocity (BFV, cm/s) was measured in the middle cerebral artery using a 2-MHz transcranial Doppler sonography system, ICP (mm Hg) was measured using an extradural probe, and MAP (mm Hg) and HR (b/min) were measured during a study period of 20 min. Cerebral perfusion pressure (CPP=MAP-ICP) was also calculated. RESULTS: Our data show that a single bolus dose of up to 4xED95 cisatracurium caused no significant (P<0.05) changes in BFV, ICP, CPP, MAP and HR. Possible histamine-related events were not observed during the study. CONCLUSIONS: The results from this study suggest that cisatracurium is a safe neuromuscular blocking agent for use in adult severe brain-injured patients with increased ICP under mild hyperventilation and continuous sedation.     

Cinematographic analysis of bovine embryo development in serum-free oviduct-conditioned medium

The effects of NG-nitro-L-arginine (NOLAG), an inhibitor of nitric oxide synthase (NOS), and of indomethacin, an inhibitor of cyclooxygenase, on the rise in cerebral blood flow (CBF) accompanying increasing levels of hypercapnia (paCO2 = 40-135 mmHg) were studied in anesthetized rats. CBF was measured by intracarotid injection of 133Xe. Progressive increases in paCO2 of 10 mmHg, at intervals of about 8-10 minutes, were associated with gradual increases in CBF until a paCO2 level of 115 mmHg was reached. No further CBF changes (from the maximum value of 446 +/- 70 ml 100 g-1 min-1) were seen with additional step increase in paCO2. Intracarotid infusion of 7.5 mg/kg NOLAG significantly attenuated the CO2-elicited CBF increase by about 45-65% at paCO2 values below 115 mmHg. Beyond this level, there was a lesser inhibition of about 27-35%. 30 mg/kg NOLAG had essentially the same effect as 7.5 mg/kg NOLAG. 50 mg/kg NOLAG, given intraperitoneally (i.p.) twice daily for 4 days, also caused an attenuated CBF response to CO2, but the inhibitory effect was significantly less than with acute NOLAG administration in the paCO2 range of 61-90 mmHg. Infusion of L-arginine, 1 g/kg/h, prevented the effect of 7.5 mg/kg NOLAG. Indomethacin, 10 mg/kg, i.v. produced a more dramatic attenuation of the response, to the extent that the steady rising curve of CBF as a function of paCO2 was almost completely abolished. With indomethacin, a moderate increase (50%) in CBF was seen at the lowest level of hypercapnia, but raising paCO2 above this level did not result in further increases in CBF. This effect could not be prevented by L-arginine. When combining 7.5 mg/kg NOLAG with 10 mg/kg indomethacin, the response to hypercapnia was totally blocked. The results suggest that NOLAG and indomethacin act through different mechanisms on the hypercapnic CBF response, and that indomethacin is the more powerful inhibitor.     

Effects of dipyridamole in spontaneously hypertensive rabbits with diffuse chronic cerebral ischemia

The effect of intravenous dipyridamole (0.7 mg/kg) on cerebral blood flow (CBF), mean arterial blood pressure (MABP), heart rate, respiration rate, cerebral electrical activity, arterial blood gases, pH, and glucose was investigated in 14 normotensive and 14 stroke-prone spontaneously hypertensive anesthetized rabbits. CBF was measured by hydrogen and heat clearance. In both groups, MABP decreased (normotensive: -24 mm Hg, hypertensive: -47 mm Hg; ANOVA: P < 0.0001) and CBF increased (normotensive: +59 ml/100 g/min, hypertensive: +72 ml/100 g/min; ANOVA: P < 0.0002). CBF returned to the initial level 21 min later in hypertensive than in normotensive rabbits. Changes in other parameters were insignificant. In additional experiments, 30 mg/kg theophylline entirely prevented the cerebral vasodilator and systemic hypotensive effects of dipyridamole in both normotensive and hypertensive rabbits. We conclude that, in stroke-prone spontaneously hypertensive rabbits, the longer-lasting and larger CBF increase in response to dipyridamole may be attributed to reversible functional changes in the cerebral vasculature resulting from hypertension.     

Antibiotic residues and their recovery from animal tissues

Cerebral blood flow (CBF) was measured by a 133Xe inhalation technique in 8 patients with chronic high spinal cord injuries. Six patients had a physiologically complete cervical cord transection and 1 subject had an incomplete C4-5 lesion but with evidence of interruption of sympathetic pathways. CBF and arterial blood pressure (BP) were measured in the supine position and then in the sitting, or feet up, position to produce a change of BP. In 4 patients CBF was measured during a suction manoeuvre applied to the lower half of the body to produce a fall of BP. There was no significant change of CBF in the patients during hypo- and hypertension. The response of CBF to hyperventilation for 5 min was measured in the supine position and did not differ significantly from that of 13 normal "control" subjects and 1 patient with a lesion at T2-3. It is concluded that the responses of the cerebral circulation to change of blood pressure and to hypocapnia are normal in patients with high spinal cord transection. The mechanisms involved in these responses are therefore independent of control via cervical sympathetic pathways.     

Cerebral blood flow measurement in patients with impaired consciousness: usefulness of 99mTc-HMPAO single-photon emission tomography in clinical practice

The relationship between impairment of consciousness and quantitative cerebral blood flow (CBF) was investigated. The mean CBF of the whole brain was measured by the Patlak-plot method using technetium-99m hexamethylpropylene amine oxime single-photon emission tomography (99mTc-HMPAO SPET) in patients with the following diseases: cerebral infarction, intraparenchymal haemorrhage, subarachnoid haemorrhage, brain tumour and cerebral contusion. The clinical symptoms were evaluated according to the severity of impaired consciousness, aphasia and dementia. Four hundred and eighty-five CBF measurements were performed. Patients with alert consciousness showed an age-related decline in mean CBF. Patients with aphasia showed a significant reduction in mean CBF compared with those without aphasia. Impaired consciousness was proportional to reduction in mean CBF regardless of types of pathology, and the size of lesion did not influence the mean CBF. Patients with dementia showed a significant reduction in mean CBF proportional to the severity of dementia. The quantitative measurement of CBF using 99mTc-HMPAO SPET is reliable in clinical evaluations.     

Effects of etomidate administration on cerebral collateral flow

OBJECTIVE: Augmentation of blood flow to collateral-dependent tissue (CDT) as a result of selective vasodilation of collateral vessels has been shown to occur with various stimuli after middle cerebral artery occlusion. Etomidate, a carboxylated imidazole derivative, is a nonbarbiturate anesthetic that is used clinically both as an anesthetic and as a neuroprotective agent. The effect etomidate has on collateral cerebral vessels is unknown. The purpose of our studies was to test whether etomidate selectively augmented cerebral blood flow (CBF) to CDT during ischemia as an additional mechanism of neuroprotection. METHODS: A left craniotomy was performed in each of 14 dogs, with the animals under halothane anesthesia. A branch of the middle cerebral artery was occluded and cannulated distally for determination of CDT using a "shadow flow" technique. CBF and vascular pressures were measured and used to calculate vascular resistance. An etomidate infusion (0.1 mg/kg of body weight/min administered intravenously) was started, and CBF and vascular pressures were measured at 10 and 40 minutes. Hypotension was then induced, and CBF and pressures were again measured. RESULTS: CBF was significantly reduced in all regions of the brain, including CDT, when etomidate was infused. CDT showed a 53.7% reduction in flow, whereas normal CBF was reduced by at least 63.4%. During hypotension, blood flow to CDT was reduced by an additional 42.7%, whereas normal cerebrum was reduced by at least 22.7%. Vascular resistance was increased in all vessels during etomidate infusion. CONCLUSION: The neuroprotective effects of etomidate do not seem to be through the augmentation of collateral or global CBF.     

Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm

The extent and timing of posttraumatic cerebral hemodynamic disturbances have significant implications for the monitoring and treatment of patients with head injury. This prospective study of cerebral blood flow (CBF) (measured using 133Xe clearance) and transcranial Doppler (TCD) measurements in 125 patients with severe head trauma has defined three distinct hemodynamic phases during the first 2 weeks after injury. The phases are further characterized by measurements of cerebral arteriovenous oxygen difference (AVDO[2]) and cerebral metabolic rate of oxygen (CMRO[2]). Phase I (hypoperfusion phase) occurs on the day of injury (Day 0) and is defined by a low CBF calculated from cerebral clearance curves integrated to 15 minutes (mean CBF 32.3 +/- 2 ml/100 g/minute), normal middle cerebral artery (MCA) velocity (mean V[MCA] 56.7 +/- 2.9 cm/second), normal hemispheric index ([HI], mean HI 1.67 +/- 0.11), and normal AVDO(2) (mean AVDO[2] 5.4 +/- 0.5 vol%). The CMRO, is approximately 50% of normal (mean CMRO(2) 1.77 +/- 0.18 ml/100 g/minute) during this phase and remains depressed during the second and third phases. In Phase II (hyperemia phase, Days 1-3), CBF increases (46.8 +/- 3 ml/100 g/minute), AVDO(2) falls (3.8 +/- 0.1 vol%), V(MCA) rises (86 +/- 3.7 cm/second), and the HI remains less than 3 (2.41 +/- 0.1). In Phase III (vasospasm phase, Days 4-15), there is a fall in CBF (35.7 +/- 3.8 ml/100 g/minute), a further increase in V(MCA) (96.7 +/- 6.3 cm/second), and a pronounced rise in the HI (2.87 +/- 0.22). This is the first study in which CBF, metabolic, and TCD measurements are combined to define the characteristics and time courses of, and to suggest etiological factors for, the distinct cerebral hemodynamic phases that occur after severe craniocerebral trauma. This research is consistent with and builds on the findings of previous investigations and may provide a useful temporal framework for the organization of existing knowledge regarding posttraumatic cerebrovascular and metabolic pathophysiology.     

delta -function bosons in a one-dimensional potential well

The neuroprotective efficacy of the hydroperoxide scavenger ebselen was assessed in a model of transient focal ischaemia that utilises the potent vasoconstrictor peptide endothelin-1 to induce temporary occlusion of the middle cerebral artery (MCA). Pretreatment with ebselen (10 or 30 mg/kg p.o., 40 min pre-MCA occlusion) dose dependently reduced the volume of ischaemic damage assessed 4 h post-endothelin-1 application in the anesthetised rat. The lower dose of ebselen (10 mg/kg) resulted in a non-significant 35% reduction in the total volume of ischaemic damage compared with the vehicle control. In contrast the higher dose of ebselen (30 mg/kg) significantly reduced the volume of ischaemic damage in the cerebral hemisphere and cerebral cortex by 48% and 53%, respectively. The marked reduction in brain damage achieved with ebselen cannot be attributed to drug-induced alterations in blood pressure, body temperature or arterial blood gases since these physiological variables were closely monitored and were not significantly altered by ebselen treatment. Thus ebselen is an effective neuroprotective agent against acute focal ischaemic-reperfusion injury.     

Cholinergic modulation of cerebral cortical blood flow changes induced by trauma

These experiments tested the role of cholinergic mechanisms in the changes of cerebral cortical blood flow (CBF) induced by brain trauma. CBF was measured with Iodo-14C-antipyrine autoradiography, in 128 cerebral cortex regions of both hemispheres, distributed in eight coronal slices. The effects of a 6.3-mm diameter craniotomy over the left motor-sensory cortex with no weight drop, and of trauma (drop weight of 20 g from 30 cm height on left motor-sensory cortex through a 6.3 mm circular craniotomy) on CBF were studied at 2 and 24 h after the interventions. A group of control animals that received no intervention was also set up. Animals were treated with the cholinesterase inhibitor physostigmine salicylate (3.3 microg/kg/min i.v. infusion started 60 min before CBF measurements), the cholinergic blocker scopolamine hydrobromide (1 mg/kg i.v. pulse, 18 min before CBF measurements), or with the drugs vehicle (saline). A focus of decreased CBF at the site of impact was observed 2 h after trauma, extending caudally as far as the occipital cortex. CBF on the contralateral cerebral cortex was also decreased. Both phenomena reversed partially at 24 h. This spontaneous recovery of CBF was blocked by scopolamine. Physostigmine reversed the decrease in CBF of the traumatized cortex, partially around the contused area and completely in more distant regions. The cerebral cortex contralateral to the trauma showed significantly higher CBF 24 h after trauma when compared to intact controls or craniotomy that peaked at the area symmetrical to the center of trauma. This phenomenon was also enhanced by physostigmine and completely blocked by scopolamine. These results suggest a prominent role of cholinergic mechanisms in the vascular adjustments that accompany cerebral trauma.     

A catecholamine-mediated increase in cerebral oxygen uptake during immobilisation stress in rats

Anxiety and grave apprehension have been supposed to increase cerebral metabolism, and it has earlier been suggested that intravenous infusion of adrenaline may increase cerebral blood flow (CBF) and cerebral oxygen consumption (CMR02). In an experimental model on rats, it could be shown that immobilisation stress increased CBF and CMR02 after 5 min (about 150% of control values) and 30 min (about 190% of control values). By previous adrenalectomy or by administration of a beta-receptor blocker (propranolol, 1.4 mg/kg) the changes in CBF and CMR02 could be prevented. It is concluded that the excessive increase in CBF and CMR02 was mediated via release of catecholamines from the adrenal glands.     

Doppler examination of cerebral arteries in uremic children

Transcranial Doppler ultrasonography is a useful method for the estimation and monitoring of cerebral circulation in dialyzed patients. The aim of this study was to evaluate the effect of disease and treatment on cerebral circulation in children on maintenance hemodialysis (HD) and children prior to renal replacement therapy. We demonstrated that in uremic children blood flow velocities of the internal carotid artery (ICA), anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) 120 min and 240 min from the beginning of an HD session were significantly lower than values immediately before HD. Changes in blood flow velocities of MCA and ACA during HD correlated significantly with changes in mean arterial pressure during HD. There was no correlation between changes in blood flow velocities and intradialytic changes in hematocrit values, ultrafiltration, hemoglobin concentration, and blood urea nitrogen values. Mean blood flow velocities of ICA, MCA, and PCA in euvolemic children on conservative treatment were significantly higher than after a HD session in children on maintenance HD. The factors responsible for intradialytic velocity changes of cerebral arteries in uremic children require further examination.     

Reduction of infarct volume by halothane: effect on cerebral blood flow or perifocal spreading depression-like depolarizations

Halothane is a strong inhibitor of potassium evoked spreading depression (SD) in cats. In the current study, we investigate halothane effects on induction of perifocal SD-like depolarizations, CBF, and infarct evolution in focal ischemia. Calomel and platinum electrodes measured cortical direct current potential and CBF in ectosylvian, suprasylvian, and marginal gyri. Left middle cerebral artery occlusion (MCAO) induced permanent focal ischemia for 16 hours in artificially ventilated cats (30% oxygen, 70% nitrous oxide) under halothane (0.75%, n = 8) or alpha-chloralose anesthesia (60 mg/kg intravenously, n = 7). Under alpha-chloralose, MCAO induced severe ischemia in ectosylvian and suprasylvian gyri(mean CBF < 10 mL/100 g/min), and direct current potentials turned immediately into terminal depolarization. In marginal gyri, CBF reduction was mild (more than 20 mL/100 g/min), and in six of seven animals, frequent SD-like depolarizations turned into terminal depolarization at a later stage of the experiments. Under halothane, MCAO induced severe ischemia (less than 10 mL/100 g/min) and immediate terminal depolarization only in ectosylvian gyrus. In suprasylvian gyrus, residual CBF remained significantly higher (more than 10 mL/100 g/min) than under alpha-chloralose, whereas in marginal gyri, CBF did not differ between groups. Compared with chloralose, the number of transient depolarizations was significantly reduced in marginal gyrus, and in suprasylvian gyrus transient but significantly longer depolarizations than in marginal gyrus were recorded. Except for one animal, transient depolarizations did not turn into terminal depolarization under halothane, and infarct volume reduction was particularly seen in suprasylvian gyrus. We conclude that halothane, the most commonly used anesthetic in studies of experimental brain ischemia, has protective properties, which may depend on both cerebrovascular and electrophysiologic influences.     

Cerebral extracellular lactate concentration and blood flow during chemical stimulation of the nucleus tractus solitarii in anesthetized rats

The extracellular lactate concentration and blood flow in the cerebral cortex of urethane-anesthetized, paralyzed and artificially ventilated rats were monitored continuously and simultaneously using an enzyme electrode and a laser Doppler flowmeter (LDF), respectively, during chemical stimulation of the nucleus tractus solitarii (NTS) by microinjection of L-glutamate (1.7 nmol 50 nl). Chemical stimulation of the NTS significantly decreased the arterial blood pressure (ABP) from 85 +/- 17 to 68 +/- 14 mmHg, heart rate from 418 +/- 13 to 402 +/- 19 beats x min(-1) and cerebral blood flow (CBF) by 17.9 +/- 6.2% (P < 0.001). However, chemical stimulation of the NTS significantly increased the lactate concentration by 58.9 +/- 17.3 microM (P < 0.001). Barostat maneuver, which held systemic ABP constant during chemical stimulation of the NTS attenuated the responses in CBF and lactate concentration by 30 and 27%, respectively. The onset of the increase in lactate concentration was delayed about 19 s after that of the CBF decrease. Circulatory lactate produced no significant change in the cerebral extracellular lactate concentration. These results indicate that chemical stimulation of the NTS induces an increase in extracellular lactate concentration in the cerebral cortex through a decrease in CBF via cerebral vasoconstriction.     

Mechanisms mediating postprandial blood pressure reduction in young and elderly subjects

The objective of this study was to clarify potential differences in hormonal, neurogenic and hemodynamic mechanisms mediating postprandial blood pressure (BP) reduction. In 12 age- and body mass index-matched young normotensive (NT) subjects, 21 elderly NT, 17 young hypertensive (EH) patients, and 32 elderly EH, we measured BP, blood glucose, plasma insulin (IRI), and norepinephrine (NE) levels before and every 30 min for 3 h after a 75 g oral glucose solution ingestion. Cardiac output (CO) and total systemic resistance (TSR) were also measured before and 1 h after oral glucose ingestion. Postprandial BP reduction, defined as 10% or more decline in mean BP was recognized in 3/12 (25%) young NT, 9/21 (43%) elderly NT, 5/17 (29%) young EH, and 20/32 (63%) elderly EH. The most consistent finding was that the IRI response to glucose was high in all subjects with postprandial BP reduction regardless of age or level of BP, although changes in blood glucose levels showed no major differences. The NE level was low in young and elderly NT with postprandial BP reduction, but in EH the level was not different. Increases in CO in elderly subjects with postprandial BP reduction was significantly less than that in subjects without postprandial BP reduction. In addition, the decrease in TSR in young subjects with postprandial BP reduction was significantly greater than that in subjects without postprandial BP reduction, while the decrease in elderly subjects was not different between the subjects with and without postprandial BP reduction. In conclusion, postprandial BP reduction in elderly EH appears to be associated with hyperinsulinemia independent of age and BP status. The vasodilator effects of insulin may contribute to postprandial BP reduction. A second conclusion is that impairment of sympathetic nervous system responses to insulin may also contribute to altered postprandial hemodynamic responses especially in EH, suggesting multiple mechanisms in origin of postprandial BP reduction.     

Changes of respiratory chain activity in mitochondrial and synaptosomal fractions isolated from the gerbil brain after graded ischaemia

In this study we have examined (1) the integrated function of the mitochondrial respiratory chain by polarographic measurements and (2) the activities of the respiratory chain complexes I, II-III, and IV as well as the ATP synthase (complex V) in free mitochondria and synaptosomes isolated from gerbil brain, after a 30-min period of graded cerebral ischaemia. These data have been correlated with cerebral blood flow (CBF) values as measured by the hydrogen clearance technique. Integrated functioning of the mitochondrial respiratory chain, using both NAD-linked and FAD-linked substrates, was initially affected at CBF values of approximately 35 ml 100 g-1 min-1, and declined further as the CBF was reduced. The individual mitochondrial respiratory chain complexes, however, showed differences in sensitivity to graded cerebral ischaemia. Complex I activities decreased sharply at blood flows below approximately 30 ml 100 g-1 min-1 (mitochondria and synaptosomes) and complex II-III activities decreased at blood flows below 20 ml 100 g-1 min-1 (mitochondria) and 35-30 ml 100 g-1 min-1 (synaptosomes). Activities declined further as CBF was reduced below these levels. Complex V activity was significantly affected only when the blood flow was reduced below 15-10 ml 100 g-1 min-1 (mitochondria and synaptosomes). In contrast, complex IV activity was unaffected by graded cerebral ischaemia, even at very low CBF levels.     

Pulsatile versus nonpulsatile cardiopulmonary bypass. No difference in brain blood flow or metabolism at 27 degrees C

BACKGROUND: It is unclear whether nonpulsatile perfusion adversely affects the brain. This study compared cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) betwen pulsatile and nonpulsatile cardiopulmonary bypass (CPB) in rabbits at 27 degrees C. METHODS: In experiment A, 24 anesthetized New Zealand white rabbits underwent pulsatile CPB at 27 degrees C, using alpha-stat acid-base management. Animals were randomized to three groups based upon the duration of the period of systolic ejection (100, 120, 140 ms) and were perfused for 20 min at each of three pulse rates (150, 200, 250 pulse/min), generating nine arterial pressure waveforms. Arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (radiolabeled microspheres), and CMRO2 (Fick) were measured at the end of each 20-min period. In experiment B, 16 anesthetized rabbits were randomized to pulsatile (120-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 27 degrees C. AFter 1 h, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF and CMRO2 were measured. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all nine waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile bypass, 30 +/- 4 versus 32 +/- 5 ml.100 g-1.min-1, respectively. CMRO2 did not differ between pulsatile and nonpulsatile bypass, 1.7 +/- 0.2 versus 1.6 +/- 0.2 ml.100 g-1.min-1, respectively. CONCLUSIONS: During CPB in rabbits at 27 degrees C, neither CBF nor CMRO2 is affected by flow character.