Effects of Intranasal Epinephrine on Cerebrospinal Fluid Epinephrine Pharmacokinetics, Nasal Mucosa, Plasma Epinephrine Pharmacokinetics, and Cardiovascular Changes.

PURPOSE: We aimed to assess intranasal (IN) epinephrine effects on cerebrospinal fluid (CSF) absorption, nasal mucosa quality, plasma epinephrine pharmacokinetics (PK), and cardiovascular changes in dogs. METHODS: CSF epinephrine concentration was measured and nasal mucosa quality was evaluated after IN epinephrine 4 mg and one or two 4 mg doses (21 min apart), respectively. Maximum plasma concentration [Cmax], time to Cmax [Tmax], area under the curve from 0 to 120 min [AUC0-120], and cardiovascular effects were evaluated after epinephrine IN (4 and 5 mg) and intramuscular (IM; 0.3 mg). Clinical observations were assessed. RESULTS: After epinephrine IN, there were no changes in CSF epinephrine or nasal mucosa. Cmax, Tmax, and AUC1-120 were similar following epinephrine IN and IM. Epinephrine IN versus IM increased plasma epinephrine at 1 min (mean ± SEM, 1.15 ± 0.48 for 4 mg IN and 1.7 ± 0.72 for 5 mg IN versus 0.47 ± 0.11 ng/mL for 0.3 mg IM). Epinephrine IN and IM produced similar heart rate and ECG results. Clinical observations included salivation and vomiting. CONCLUSIONS: Epinephrine IN did not alter CSF epinephrine or nasal tissue and had similar cardiovascular effects as epinephrine IM. Epinephrine IN rapidly increased plasma epinephrine concentration versus epinephrine IM.

Monoamine metabolites in ventricular CSF of children with posterior fossa tumors: correlation with tumor histology and cognitive functioning.

OBJECT: The biogenic amines (dopamine, epinephrine, norepinephrine, and serotonin) are involved in the regulation of multiple neuronal functions, and changes in monoamine concentrations in the CSF have been detected in several disorders. The aim of the present study was to investigate the role of biogenic amines in the ventricular CSF of children suffering from posterior fossa tumors and their possible correlation with tumor histology and cognitive functioning. METHODS: Twenty-two children with posterior fossa tumors who were treated surgically at Children's Hospital "Agia Sofia" were studied. Patients ranged in age from 5.5 to 15 years. The study population included patients who suffered from hydrocephalus and were treated by ventriculoperitoneal shunt placement. During the operation for shunt placement, a CSF sample was obtained for the assessment of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). Simultaneously, a blood sample was also obtained for assessment of the same metabolites in the serum. The concentration of vanillylmandelic acid (VMA) was evaluated in 24-hour urine samples in 11 patients. Cerebrospinal fluid from a control group of children was also studied. Executive functions were assessed using the short form of the Wechsler Intelligence Scale for Children (WISC). RESULTS: Twelve patients suffered from astrocytomas, 9 from medulloblastomas, and 1 from an ependymoma. The MHPG concentration in CSF was significantly higher in patients with astrocytomas compared with patients with medulloblastomas. Twenty-four-hour urine samples of VMA were significantly higher in patients with astrocytomas compared with patients with medulloblastomas. The MHPG concentration in CSF was negatively correlated with the verbal scale of the WISC and there was a trend toward a significant negative correlation with the total WISC score. Homovanillic acid in CSF was positively correlated with the performance scale of the WISC. There was a significant correlation between HVA and MHPG levels in CSF. The CSF concentration of 5-HIAA was significantly correlated with the HVA concentration in serum. Twenty-four-hour urine VMA samples were statistically significantly correlated with HVA concentration in both CSF and serum, with MHPG in CSF, and with 5-HIAA in serum. CONCLUSIONS: This study showed that children with posterior fossa tumors have differences in the levels of monoamine metabolites in CSF. Further studies with a larger number of patients are obviously needed to verify these observations as well as studies to correlate the monoamine metabolite levels with the neuropsychological and behavioral findings in children with posterior fossa tumors.

Association between acute sympathetic response, early onset vasospasm, and delayed vasospasm following spontaneous subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is accompanied by a marked acute sympathetic response, and evidence exists for sympathetic participation in the development of cerebral vasospasm (VS). The purpose of this observational investigation was to assess the association between acute central catecholaminergic activity, early VS and delayed VS following SAH. SAH grade 3-5 patients who received ventriculostomy, and in whom bilateral temporal transcranial insonation was performed, were enrolled. Cerebrospinal fluid (CSF) was sampled (<48 hours) and assayed for catecholamines, which were correlated to measures of early and delayed sonographic anterior circulation VS. Clinical independent predictors of early VS included age (odds ratio .946 [95% confidence interval .902-.991]), CT scan score (4.27 [1.30-14.0]) and neurogenic cardiomyopathy (6.5 [1.24-34.1]). Age (.925 [.859-.996]) and CT scan score (8.30 [1.33-5.17]) also independently predicted delayed VS. Any early VS independently predicted conventionally defined delayed VS (10.9 [2.64-45.0]), and severe delayed VS was independently predicted by any early VS (9.87 [2.45-39.7]) and by conventionally defined early VS (12.3 [2.80-54.1]). The norepinephrine:3,4-dihydroxyphenylglycol ratio (NE/DHPG) independently predicted severe delayed VS (3.38 [1.01-11.35]), for which DHPG was a negative predictor (.356 [.151-.839]). Epinephrine was a negative predictor of any early VS (.574 [.357-.921]), any delayed VS (.372 [.158-.875]), and delayed conventional VS (.402 [.200-.807]). Early and delayed VS appear to be related processes that are generally unrelated to the acute central sympathetic response following SAH. The one exception may be severe delayed VS which may be associated with noradrenergic activation.

Molecularly imprinted micro solid-phase extraction technique coupled with complementary molecularly imprinted polymer-sensor for ultra trace analysis of epinephrine in real samples.

A simple hyphenation approach was adopted to obtain a new molecularly imprinted micro solid-phase extraction fiber (as a selective extraction tool) and complementary molecularly imprinted polymer coated pencil graphite electrode (as a detection tool) for the selective and sensitive analysis of epinephrine, which is a disease biomarker prevalent at ultra trace level in biological fluids. In both extraction and detection processes, the functionalized multiwalled carbon nanotubes (CNT-mers) were preferred to multiwalled carbon nanotubes (unmodified) in order to obtain a stable homogeneously dispersed imprinted polymer matrix of better electroconductivity and adsorptive characteristics. The hyphenation of both tools helped dual pre-concentration of epinephrine so as to achieve the stringent limit [limit of detection: 0.002 ng mL(-1), S/N=3] of clinical detection, without any problems of non-specific contributions and cross-reactivity.

Determinants of central sympathetic activation in spontaneous primary subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) has been associated with pronounced acute sympathetic activation. The purpose of this investigation is to identify demographic, clinical, radiological, and anatomical features of SAH that relate to sympathetic activation. METHODS: Observational study of consecutive Grades 3-5 SAH patients requiring ventriculostomy and undergoing endovascular aneurysmal obliteration. All patients underwent cerebrospinal fluid (CSF) sampling within 48 h of SAH onset, and samples were assayed for various catecholamine compounds and metabolites. Univariate analyses were performed to identify variables associated with catecholamine levels, and to correlate linearity among catecholamine compounds and metabolites. Variables demonstrating a possible association and variables of interest were entered into linear regression models to determine predictors of catecholamine elevations. RESULTS: Of the 102 patients, mean age was 58 years and 74% were female; 42% were Hunt-Hess (H/H) grade 4/5, 61% had a computed tomography (CT) score of 3/4, 57% had anterior cerebral or communicating artery (ACA/ACom) aneursysms, and 23% had aneurysms in the posterior circulation. In the univariate analysis, age, gender, H/H grade, CT score, and aneurysm location demonstrated various associations with catecholamine levels, and substantial positive correlations existed between the various catecholamine compounds and metabolites. Linear regression analyses revealed H/H grade to be an independent predictor of elevated CSF epinephrine (EPI), 3,4-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenyl acetic acid (DOPAC) levels, and of the norepinephrine/3,4-dihydroxyphenylglycol (NE/DHPG) ratio (p < 0.05 for all analyses). Female gender independently predicted increased dopamine (DA) and DOPAC levels (p < 0.05 for two analyses), as well as possibly DOPA levels (p < 0.1). Age, CT score and aneurysm location demonstrated only inconsistent associations and trends. CONCLUSIONS: Central sympathetic activation relates to clinical severity and female gender. No definitive associations were found for age, hemorrhage amount, or aneurysm location.

CSF catecholamine profile in subarachnoid hemorrhage patients with neurogenic cardiomyopathy.

BACKGROUND: Patients experiencing apoplectic intracranial processes may develop neurogenic cardiomyopathy (NC). The purpose of this research is to determine whether cerebrospinal fluid (CSF) catecholamine levels are elevated in subarachnoid hemorrhage (SAH) patients with NC when compared to those without NC. METHODS: Observational study of consecutive grades 3-5 SAH patients requiring ventriculostomy. All patients underwent CSF sampling for catecholamine levels, and transthoracic echocardiography (TTE) to assess for NC, within 48 h of SAH onset. Univariate analyses were performed to identify clinical and laboratory variables associated with NC. Clinical variables associated with NC in the univariate analysis were entered into logistic regression models along with the candidate catecholamine variables to identify predictors of NC. RESULTS: The study group contained 100 patients--mean age of study subjects was 58 years, 73% were female, and 15% developed NC. NC patients were more likely to have a worse clinical grade than patients without NC (80 vs. 34%, P = 0.001). NC patients possessed greater DOPA levels (5.83 vs. 4.60 nmol/l, P = 0.044), and a trend toward greater noradrenergic activity as determined by NE/DHPG ratio (0.3799 vs. 0.2519, P = 0.073). Multivariate analysis identified worse clinical grade (OR 7.09, P = 0.005) and possibly NE levels (OR 1.005, P = 0.057) as independent predictors of NC. Bivariate analysis reinforced the findings for NE (OR 1.006, P = 0.022), and also identified DOPA levels (OR 1.001, P = 0.034) and NE/DHPG (OR 22.18, P = 0.019) as predictors of NC. CONCLUSIONS: SAH patients with NC tend to have greater CSF catecholamine levels than those without NC. However, the development of NC may also be related to factors not evaluated by our study.

A history of iron deficiency anemia during infancy alters brain monoamine activity later in juvenile monkeys.

Both during and after a period of iron deficiency (ID), iron-dependent neural processes are affected, which raises the potential concern that the anemia commonly experienced by many growing infants could have a protracted effect on the developing brain. To further investigate the effects of ID on the immature brain, 49 infant rhesus monkeys were evaluated across the first year of life. The mothers, and subsequently the infants after weaning, were maintained on a standardized diet containing 180 mg/kg of iron and were not provided other iron-rich foods as treats or supplements. As the infants grew, they were all screened with hematological tests, which documented that 16 (33.3%) became markedly ID between 4 and 8 months of age. During this anemic period and subsequently at 1 year of age, cerebrospinal fluid (CSF) specimens were collected to compare monoamine activity in the ID and iron-sufficient infants. Monoamine neurotransmitters and metabolite levels were normal at 4 and 8 months of age, but by 1 year the formerly anemic monkeys had significantly lower dopamine and significantly higher norepinephrine levels. These findings indicate that ID can affect the developmental trajectory of these two important neurotransmitter systems, which are associated with emotionality and behavioral performance, and further that the impact in the young monkey was most evident during the period of recovery.

Perioperative concentrations of catecholamines in the cerebrospinal fluid and plasma during spinal anesthesia.

BACKGROUND: Catecholamine release is a physiological response to stress. The extent to which perioperative stress provokes the central release of catecholamines, which modulate pain perception in the spinal cord, still remains unknown. The perioperative course of catecholamine concentrations in the cerebrospinal fluid (CSF) and plasma was examined. METHODS: A prospective study was performed in 25 patients (ASA III, 60-84 years) undergoing elective hip joint replacement in spinal catheter anesthesia. The concentrations of dopamine, epinephrine and norepinephrine in the CSF and plasma were measured before anesthesia, immediately after surgery, and 6 and 24 h post-operatively. RESULTS: In most patients, dopamine and epinephrine were not detectable in CSF. CSF-norepinephrine concentrations decreased from median [interquartile-range] 159 [124;216] pre-anesthesia to 116 [79;152] pmol/l immediately post-operatively and were slightly elevated 24 h post-operatively (180 [134;302] pmol/l) (P=0.05). Dopamine plasma concentrations were not detectable or were barely above the detection threshold. Plasma epinephrine increased from 61 [28;77] pmol/l pre-anesthesia to 112 [69;138] pmol/l 6 h post-operatively and returned to baseline 24 h post-operatively (P=0.001). Plasma norepinephrine concentrations increased intra-operatively from 298 [249;422] to 556 [423;649] pmol/l and remained elevated 24 h after surgery (P=0.009). There was no association between changes in CSF or plasma norepinephrine or epinephrine concentrations and changes in heart rate (HR) or mean arterial pressure (MAP). CONCLUSION: During spinal anesthesia for elective hip joint replacement, norepinephrine concentrations were greater in plasma than in CSF. CSF dopamine and epinephrine concentrations were essentially undetectable. The changes in CSF-norepinephrine concentrations and the changes of plasma norepinephrine concentrations showed no association with each other; nor were there correlations between clinical stress parameters (HR, MAP) or visual analog scale pain, and the changes in CSF norepinephrine concentrations.

The dopaminergic neurotransmitter system is associated with aggression and agitation in frontotemporal dementia.

To identify neurochemical correlates of behavioral and psychological signs and symptoms of dementia (BPSD), we set up a prospective study. Patients with probable Alzheimer's disease (AD) (n=181), mixed dementia (MXD) (n=28), frontotemporal dementia (FTD) (n=25) and dementia with Lewy bodies (DLB) (n=24) were included. At inclusion, all patients underwent lumbar puncture, neuropsychological examination and behavioral assessment (battery of behavioral assessment scales). Cerebrospinal fluid (CSF) levels of norepinephrine and of (nor)epinephrine (MHPG), serotonin (5HIAA) and dopamine (DOPAC, HVA) metabolites were determined by HPLC and electrochemical detection. Spearman Rank-Order followed by Bonferroni correction was used for calculating correlations. In FTD patients, CSF norepinephrine levels were positively correlated with dementia severity (r=0.539; p=0.021). CSF DOPAC levels were correlated with BPSD in general (r=0.537; p=0.007), associated caregiver burden (r=0.567; p=0.004) and agitated and aggressive behavior (r=0.568; p=0.004). In a subgroup of FTD patients who did not receive psychotropic pharmacological treatment, a strong correlation between CSF HVA/5HIAA ratios (reflecting serotonergic modulation of dopaminergic neurotransmission) and aggressive behavior (r=0.758; p=0.009) was found. In MXD patients, (verbally) agitated behavior was positively associated with the turnover of norepinephrine (r=0.633; p=0.002). No significant correlations were found in AD and DLB groups. In FTD, increased activity of dopaminergic neurotransmission and altered serotonergic modulation of dopaminergic neurotransmission is associated with agitated and aggressive behavior respectively. This study demonstrated that neurochemical mechanisms underlying the pathophysiology of BPSD are both BPSD-specific and disease-specific which might have implications for future development of new and more selective pharmacological treatments of BPSD.

[Catecholamine levels in plasma and cerebrospinal fluid of neurosurgical patients with normal and elevated intracranial pressure]. / Plasma- und Liquor-Katecholamin-Konzentrationen neurochirurgischer Patienten mit normalem und erhöhtem Hirndruck.

OBJECTIVE: Catecholamine levels in the plasma and cerebrospinal fluid of 21 neurosurgical patients with hydrocephalus and with normal and elevated intracranial pressure were determined prospectively in a clinical study. METHODS: The study comprised 11 patients with normal intracranial pressure (8 female, 3 male, group 1) and 10 patients with elevated intracranial pressure (6 female, 4 male, group 2). The patients underwent a ventriculo-peritoneal shunt operation, external ventricular drainage or ventriculocisternostomy. The measuring times were set as follows: time 1: pre-operative; time 2: intra-operative; time 3: post-operative. The anaesthetic for the operations was administered as a total intravenous anaesthesia with propofol and alfentanil, muscle relaxation being achieved with rocuronium bromide or cis-atracurium. RESULTS: Measurements of the catecholamine levels (adrenaline, noradrenaline and dopamine) at the three set times revealed an intra-operative fall compared to the initial pre-operative value and a rise in the catecholamine level again after the operation. It is likely that this largely reflects the course of the anaesthetic. The fall in the plasma catecholamine level was much slighter in group with elevated intracranial pressure. But in the group of patients with elevated intracranial pressure the catecholamine levels found in the plasma were much higher than those of the patients without elevated pressure. In the case of adrenaline, it was possible to demonstrate a statistically significant difference at the three measuring times. This suggests that especially the analyzed adrenaline level in the plasma could take on the role of a marker in cases of elevated intracranial pressure. In group 2, with elevated intracranial pressure, the catecholamine levels in the cerebrospinal fluid (CSF) were considerably higher than those in group 1, but the difference did not reach the significance level. The lack of correlation between the catecholamine values in the plasma and CSF described in the literature (comparison of the corresponding values at time 2) was confirmed for noradrenaline and dopamine in patients with elevated intracranial pressure (group 2). In both groups of patients there was a CSF plasma gradient for dopamine at time 2, i. e. the dopamine level was higher in cerebrospinal fluid than in the plasma. CONCLUSION: The study shows that even a slight rise in intracranial pressure without clinically detectable ischaemia may result in elevated plasma and CSF catecholamine levels. Although catecholamine values are not routine parameters, they can be used in developing procedures to protect the brain in neurosurgical patients.

Effects of intraventricular methotrexate on folate, adenosine, and homocysteine metabolism in cerebrospinal fluid.

Methotrexate (MTX) is an antifolate that affects many metabolic pathways. MTX may cause neurologic toxicity, but the biochemical effects of MTX on the central nervous system (CNS) are poorly characterized. The authors studied serial cerebrospinal fluid (CSF) samples from a child during two courses of intraventricular MTX and found a rapid and reproducible depletion in CSF of reduced folates and S-adenosylmethionine that was accompanied by marked increases in homocysteine and adenosine. No sulfur-containing excitatory amino acids were detected. This study demonstrates multiple profound effects of MTX on CNS metabolism and provides insight to the pathogenesis of MTX neurotoxicity.

Monoamine metabolism and sympathetic nervous activation following subarachnoid haemorrhage: influence of gender and hydrocephalus.

Subarachnoid haemorrhage is a serious condition, often accompanied by cerebral vasospasm and hydrocephalus, which may result in delayed cerebral ischaemia and neurological deterioration. While the mechanisms responsible remain unknown, activation of the sympathetic nervous system, leading to elevated levels of circulating catecholamines is, at least in part, implicated. In this study, we sought to examine the importance of sympathetic nervous activation and its relation to brain monoaminergic neurotransmission in 25 patients following subarachnoid haemorrhage by examining plasma and cerebrospinal fluid levels of the catecholamines noradrenaline, adrenaline and dopamine, and their metabolites. Total body sympathetic activity was concurrently assessed using isotope dilution methodology. In the early phase following subarachnoid haemorrhage patients exhibited markedly elevated rates of spillover of noradrenaline to plasma (9.11 +/- 1.12 vs. 3.39 +/- 0.26 nmol/min, p < 0.01), with rates being higher in those patients in whom hydrocephalus developed (11.15 +/- 1.40 vs. 7.90 +/- 1.41 nmol/min, p = 0.05). The degree of sympathetic nervous activation tended to be higher in females compared with males. Lower cerebral perfusion pressures were observed in those patients in whom cerebrospinal fluid concentrations of noradrenaline and dopamine metabolites were high. A marked sympathetic nervous activation, more pronounced in women and in those with hydrocephalus, occurs following subarachnoid haemorrhage. The diminished cerebral perfusion seen following subarachnoid bleeding may occur as a result of activation of central catecholaminergic neurones.

Cerebrospinal fluid epinephrine in Alzheimer's disease and normal aging.

Central nervous system (CNS) adrenergic systems are involved in regulation of behavior and blood pressure. The effects of Alzheimer's disease (AD) and normal aging on resting CNS adrenergic activity were estimated by measuring cerebrospinal fluid (CSF) epinephrine (EPI) concentrations in 74 persons with AD, 42 cognitively normal healthy older persons, and 54 healthy young persons. The responsiveness of CSF EPI to the alpha-2 adrenergic antagonist yohimbine and the alpha-2 adrenergic agonist clonidine was measured in smaller subject groups. Resting CSF EPI was higher in AD than in older or young subjects, and increased with dementia severity in AD subjects. There was no relationship between resting CSF EPI and blood pressure. CSF EPI increased following yohimbine in AD and older subjects but not in young subjects. CSF EPI was unaffected by clonidine in all subject groups. The agitation increase following yohimbine was substantially greater in AD subjects than in older or young subjects. CNS adrenergic activity seems increased in AD, may further increase as AD progresses, and may be involved in the pathophysiology of agitation.

Cerebrospinal fluid neuropeptides and monoaminergic transmitters in patients with trigeminal neuralgia.

The pathogenesis of trigeminal neuralgia remains largely unknown. "Peripheral" as well as "central" causes have been suggested. To investigate the role of serotonergic, noradrenergic, dopaminergic, and peptidergic systems, we determined the concentrations of epinephrine, norepinephrine, and their breakdown product, vanillylmandelic acid, in the cerebrospinal fluid of 16 patients (55.3 +/- 8.3 years) with trigeminal neuralgia. As a marker for the dopaminergic system, we determined cerebrospinal fluid concentrations of dopamine and its metabolite, homovanillic acid. As a marker for the serotonergic system, we measured cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic acid. In addition, levels of the neuropeptides, substance P and somatostatin, were determined. The concentration of norepinephrine (P < 0.01) and its metabolite, vanillylmandelic acid, (P < 0.05) were significantly decreased in our patients. The level of the dopamine metabolite, homovanillic acid, was also significantly reduced (P < 0.01). Also significantly decreased was 5-hydroxyindoleacetic acid (P < 0.01). Substance P was significantly elevated (P < 0.05). Somatostatin was significantly decreased (P < 0.05). We hypothesize that the sum of complex neurochemical changes plays a role in the pathogenesis of trigeminal neuralgia. The elevated substance P could support the concept of a neurogenic inflammation in the trigeminovascular system, whereas changes in the monoaminergic transmitters and their metabolites seem to reflect a more central dysfunction possibly due to a longer duration of the disease and an accompanying depression.

CSF and plasma concentrations of free norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), 3,4-dihydroxyphenylalanine (DOPA), and epinephrine in Parkinson's disease.

OBJECTIVE: To investigate endogenous cerebrospinal fluid catecholamines in Parkinson's disease. MATERIAL AND METHODS: Basal concentrations of free norepinephrine (NE), dopamine (DA), epinephrine (E), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) in cerebrospinal fluid (csf) and plasma were measured using reverse-phase HPLC with electrochemical detection in 16 patients with Parkinson's disease and 21 control patients with low back pain. RESULTS: Parkinsonian patients had significantly decreased values of csf NE and DOPAC, the strong relationship between plasma and csf NE was disrupted and neither was there any age related increase of plasma NE. In l-DOPA treated patients plasma DA and DOPA concentrations were raised and csf DOPAC values were inversely related to severity of disease (Hoehn and Yahr score). Csf E concentrations were also reduced in parkinsonian patients whereas csf DA concentrations were unchanged. Csf DOPA concentrations were insignificantly decreased in parkinsonian patients. CONCLUSIONS: These results point towards a diffuse neuronal dysfunction in Parkinson's disease and indicate that lumbar csf NE and csf DOPAC are of central nervous origin.

Effects of propranolol pretreatment on cerebral blood flow, oxygen uptake and catecholamines during metabolic acidosis following E. coli endotoxin in dogs.

After an intravenous injection of E. coli endotoxin in dogs a decrease in cerebral blood flow (CBF) and an increase in cerebral metabolic rate of oxygen (CMRo2) have been shown to occur. In metabolic acidosis following endotoxin CMRo2 increased with decreasing pH. A possible explanation for the increased CMRo2 after endotoxin and metabolic acidosis seems to be a damage of the blood-brain barrier (BBB) by endotoxin. This gives possibilities for a leakage of hydrogen ions and circulating monoamines from the blood to the brain, thus affecting the cerebral blood flow and metabolism. The effects of an E. coli endotoxin injection on CBF and CMRo2 during metabolic acidosis and beta-adrenoceptor blockade were studied in eight anaesthetized dogs. All the dogs were pretreated with propranolol (PPL), per os 12.5 mg.kg-1 twice a day for one week. Metabolic acidosis (pH 7.01-7.30) was achieved by an intravenous infusion of hydrochloric acid. Endotoxin E. coli lipopolysaccharide O 111:B 4 was given as an intravenous injection of 1 mg.kg-1 bodyweight over a 5 min period. Another five animals, published earlier, with the same experimental protocol but without PPL, constituted a control group. After endotoxin no increase in CMRo2 or CBF was observed with increasing acidosis in the PPL-group. In the control group, after endotoxin, both CBF and CMRo2 increased with decreasing pH. This resulted in a significant difference in both CBF and CMRo2 between the groups in the pH range 7.01-7.15. The present results indicate that the increase in CMRo2 and CBF with metabolic acidodis in endotoxinaemia is mediated via beta-adrenoceptors.

Effects of arterial hypoxia and beta-adrenoceptor blockade on cerebral blood flow and oxygen uptake following E. coli endotoxin in dogs.

Earlier studies in normoxia have shown that an endotoxin injection in dogs leads to an increase in cerebral metabolic rate of oxygen (CMRo2), a decrease in cerebral blood flow (CBF) and increased concentrations of monoamines in blood and cerebrospinal fluid (CSF). In animals pretreated with propranolol (PPL) the CMRo2 increase was abolished and thus beta-adrenoceptor mediated. Arterial hypoxia normally increases CBF without any influence on CMRo2. The aim of this study was to investigate the effects of moderate arterial hypoxia on CBF, CMRo2 and catecholamine concentrations in blood and CSF after endotoxin with and without pretreatment with PPL. Three groups of dogs were studied. Group 1: Six animals were subjected to arterial hypoxia without any other intervention. Group 2: Six animals were given an endotoxin injection (E. coli lipopolysaccharide O 111: B 4), before the induction of hypoxia. Group 3: Eight animals were pretreated with PPL per os, 12.5 mg.kg-1 twice a day for one week before the experiments, and the effects of arterial hypoxia were studied both before and after an intravenous injection of endotoxin. Two levels of hypoxia were studied; oxygen saturation in arterial blood aiming at 75 and 50%. Endotoxin was given intravenously in a dose of 1 mg.kg-1 bodyweight over a 5 minute period. After an endotoxin injection, the response to arterial hypoxia was an increase in CMRo2, in contrast to the unchanged CMRo2 without endotoxin. After pretreatment with PPL the increase in CMRo2 after endotoxin was prevented. The CBF reaction to hypoxia was uniformly an increase.(ABSTRACT TRUNCATED AT 250 WORDS)

Separación de aminas biogénicas mediante cromatografía líquida de alta resolución / High-performance liquid chromatographic determination of biogenic amines

En este trabajo se han compilado los distintos modos cromatográficos y sistemas de detección utilizados en la cromatografía líquida de alta resolución de aminas biogénicas. Se indican las características generales del intercambio catiónico, fase reversa, fase reversa de pares iónicos y cromatografía de partición con fase reversa de pares iónicos. También se analizan comparativamente la detección UV, detección fluorimétrica usando fluorescencia nativa o bien derivatización pre- y postcolumna y detección electroquímica de gran utilidad para esta extensa familia de compuestos. Se dan ejemplos de aplicación de interés en el campo bioquímico-clínico, con el análisis de ácido homovainillínico, ácido 3,4-dihidroxifenilacético y ácido 5-hidroxiindolacético en líquido cefalorraquídeo, metanefrinas, ácido 3,4-dihidroxifenilacético, catecolaminas, ácidos urinarios y 3-metoxi-4-hidroxifenilglicol en orina, catecolaminas y 3-metoxi-4-hidroxifenilglicol en plasma, catecolaminas, 3-metoxi-4-hidroxifenilglicol y otros neurotransmisores en cerebro de rata. Se discuten, también, los tratamientos previos requeridos especialmente para orina y plasma, así como las condiciones de conservación y su incidencia en los resultados obtenidos

Separación de aminas biogénicas mediante cromatografía líquida de alta resolución / High-performance liquid chromatographic determination of biogenic amines

En este trabajo se han compilado los distintos modos cromatográficos y sistemas de detección utilizados en la cromatografía líquida de alta resolución de aminas biogénicas. Se indican las características generales del intercambio catiónico, fase reversa, fase reversa de pares iónicos y cromatografía de partición con fase reversa de pares iónicos. También se analizan comparativamente la detección UV, detección fluorimétrica usando fluorescencia nativa o bien derivatización pre- y postcolumna y detección electroquímica de gran utilidad para esta extensa familia de compuestos. Se dan ejemplos de aplicación de interés en el campo bioquímico-clínico, con el análisis de ácido homovainillínico, ácido 3,4-dihidroxifenilacético y ácido 5-hidroxiindolacético en líquido cefalorraquídeo, metanefrinas, ácido 3,4-dihidroxifenilacético, catecolaminas, ácidos urinarios y 3-metoxi-4-hidroxifenilglicol en orina, catecolaminas y 3-metoxi-4-hidroxifenilglicol en plasma, catecolaminas, 3-metoxi-4-hidroxifenilglicol y otros neurotransmisores en cerebro de rata. Se discuten, también, los tratamientos previos requeridos especialmente para orina y plasma, así como las condiciones de conservación y su incidencia en los resultados obtenidos (AU)