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Biomedical subjects

H L Edmonds

Publications and source records attributed to H L Edmonds.

At least 55 records · Page 3Linked to original sources

Lidocaine depresses synaptic activity in the rat hippocampal slice.

The direct effect of the local anesthetic lidocaine was studied using the hippocampal slice preparation in order to assess the involvement of this structure in lidocaine-induced seizure activity. Changes in the evoked field potential amplitude and latency were used to measure the effect of the drug. A dose-dependent depression of the evoked field potentials was observed at lidocaine concentration of 10(-4)M and greater. No synchronized population bursting (seizures) was observed at any of the concentrations tested (10(-6)M to 10(-3)M). However, the hippocampal slice preparation is capable of producing seizure activity, as was demonstrated following application of penicillin G. The results suggest that the hippocampus is not the site of lidocaine-induced seizure activity.

Animals↗

Effects of aerosolized methylprednisolone on experimental neurogenic pulmonary injury.

We examined the effects of graded doses of methylprednisolone sodium succinate (MPSS)--0.05 (low), 0.5 (medium), and 5 mg/kg/hour (high)--on the development of neurogenic pulmonary injury in rabbits. The aerosolized drug was administered intratracheally for 5 hours beginning 10 minutes after a 2-minute elevation of the cerebrospinal fluid pressure (Pcsf) to 250 mm Hg. Compared to untreated control animals, the percentage of increase in pulmonary capillary permeability, as determined by 51Cr-labeled ethylenediaminetetraacetic acid clearance, was significantly less in the low and high dose MPSS groups. However, high dose MPSS was also associated with a significant decrease in compliance and increase in tissue hemorrhage (quantified by visual inspection). These results indicate biphasic effect of MPSS on alveolar capillary integrity after elevated Pcsf. The low dose minimized the extent of lung hemorrhage, pulmonary capillary leakage, and loss of lung compliance. In contrast, the high dose accelerated tissue hemorrhage and compliance loss, even though pulmonary capillary permeability was maintained near base line rates.

Administration, Intranasal↗

Measurement of ischemic changes in cerebral blood flow by the hydrogen clearance technique and brain cortical temperature. Influence of flunarizine.

In dogs global cerebral ischemia was produced by clamping reversibly the left subclavian and brachiocephalic arteries, supplying the head. The intercostal arteries were ligated permanently. Cerebral blood flow (CBF) was measured discontinuously using a hydrogen saturation-desaturation technique. Clamping of the former two vessels caused an increase in systemic blood pressure. When this increase was not blunted by previous splenectomy and blood withdrawal a still important CBF remained during the clamp. However, if this rise in blood pressure was impaired, CBF decreased to 9 +/- 8% (mean +/- S.D., n = 14) of the pre-ischemic value. Flunarizine is known to have anti-hypoxic/ischemic properties. The influence of this drug (0.1 mg/kg i.v.), injected 10 min after the beginning of a 30-min ischemia period, on the post-ischemic CBF was investigated. Two-three hour after ischemia CBF was significantly lower in the solvent-treated animals than in the flunarizine-treated group, in which CBF approached the preischemic values. Changes in CBF were also followed continuously by measurement of the variations of brain versus aortic temperature. It was analyzed what information this can provide on CBF.

Animals↗

Impaired antibiotic entry into lung tissue following acid injury.

The purpose of this study was to compare the lung tissue burden of intravenous (i.v.) and intrabronchial (i.b.) cefazolin, using a standardized hydrochloric acid injury to the lungs. Ten mongrel dogs were anesthetized with pentobarbital and artificially ventilated. Following administration of cefazolin i.v. (N = 5) or i.b. (N = 5), lung biopsies were obtained at 6 hourly intervals. Simultaneous serum levels were also determined. The effective time (Teff) was defined as the period during which all serum and lung specimens demonstrated antibiotic activity exceeding 8 mcg/gm. These levels should provide comprehensive coverage of common lung and wound pathogens that are sensitive to cefazolin. Teff for the i.v. group was 1 hour, while aerosolized cefazolin never produced lung levels exceeding 8 mcg/gm. Thus, these findings suggest an explanation for cefazolin failure in gram negative pneumonia.

Aerosols↗

Computerized monitoring of the EMG and EEG during anesthesia. An evaluation of the anesthesia and brain activity monitor (ABM).

An intraoperative evaluation was made of the electroencephalographic (EEG) and electromyographic (EMG) functions of the Anesthesia and Brain activity Monitor (ABM). This device derives both these measures from a single electrode pair that is typically placed on the mid-forehead and mastoid process. The evaluation consisted of 1) quantifying the zero-crossing frequency (ZXF) of the EEG and mean integrated voltage of both measures (MIVEEG and MIVEMG) that occurred during induction and emergence from general anesthesia in 17 patients and 2) case reports sampled from an additional 41 patients. Alone or combined, variations in these parameters did not consistently accompany changes in the depth or adequacy of anesthesia as determined by standard clinical signs (e.g. heart rate, blood pressure, movement). Interpatient variability in the EEG measures during recovery from anesthesia was so large that neither the absolute value of ZXF nor that of MIVEEG could discriminate between moderate (i.e., maintenance) and light (i.e., emergence) anesthesia. Although MIVEMG uniformly decreased in anesthetized, unparalyzed patients (compared to the pre-operative awake state), noticeable increases during recovery often did not occur until limb movement was observed. Additionally, the common use of neuromuscular blockers made interpretation of low MIVEMG values quite difficult during anesthesia maintenance. However, selected individual case reports illustrated the potential benefit of routine intraoperative, microprocessor-based EEG/EMG monitoring. The single channel EEG/EMG display of the ABM seems sufficient to warn the anesthesiologist of pathologic decreases in cerebral electrical activity. Marked depression of cerebral function is associated with accidental anesthetic overdose, hypoxia or global ischemia. Additionally, the device should be useful for monitoring burst-suppression or isoelectric EEG patterns intentionally produced during barbiturate or isoflurane coma for cerebral protection.

Adolescent↗

A dual chamber for comparative studies using the brain slice preparation.

A dual linear-flow chamber for comparative studies using brain slices is described. Electrophysiological and ultrastructural analysis of rat hippocampal slices incubated in the chamber showed that its two compartments allows performance of reliable paired comparison studies in a highly efficient manner.

Anaerobiosis↗

Improved short-term neurological recovery with flunarizine in a canine model of cardiac arrest.

A 10-minute cardiac arrest was produced in dogs by electrical fibrillation of the heart. Recovery of cerebral function was monitored by estimating the cerebral metabolic rate of oxygen consumption (CMRO2), cerebral blood flow (CBF), electroencephalograph (EEG) and extent of neurological deficit. The study group received flunarizine (0.1 mg/kg intravenously) at the beginning of resuscitation, while control animals were given the drug vehicle. By four hours after resuscitation, CMRO2 in flunarizine-treated dogs was 121 +/- 43% of pre-arrest baseline, as compared with 37 +/- 9% in control animals (P less than 0.02). In the flunarizine group, CBF was 83 +/- 21% of baseline, while it was only 31 +/- 8% in controls (P less than 0.01). As compared with the control group, no other significant changes were detected in electrocardiographic, hemodynamic, or biochemical parameters in the flunarizine-treated dogs. A significant improvement in the visual EEG score (P less than 0.001) and neurological deficit (P less than 0.05) was seen in flunarizine-treated dogs six hours after ischemic insult.

Animals↗

Effects of flunarizine on recovery of cerebral function following cardiac arrest.

A 10-min cardiac arrest was produced in alfentanil-anesthetised dogs by electrical fibrillation of the heart. Recovery of cerebral function was monitored by 3 separate EEG techniques and visual assessment of neurologic deficit. The EEG techniques were visual scoring, broad-band power spectral analysis and period-amplitude analysis. The treatment group (n = 8) received flunarizine (0.1 mg/kg i.v.) at the beginning of resuscitation, while control animals (n = 8) were given the drug vehicle. A significant improvement in the visual EEG score and neurologic deficit 6 h after insult was noted in flunarizine-treated dogs. The extent of neurologic recovery was significantly correlated with the visual EEG score, with the relative power in the alpha frequency band (7.5-13.5 c/s) and with the percentage of zero-cross frequency.

Animals↗

Resistance to hypoxia in the rat hippocampal slice.

Rat hippocampal slices showed marked local variations in sensitivity to hypoxia within the CA1 region, judged by electrical criteria. There were also marked differences between slices, judged both by electrical and histological criteria. Local differences were attenuated by 'adapting' slices for 3-4 h in a uniformly oxygenated bath before testing. The local differences may reflect proximity to capillaries.

Animals↗

The stability of the hippocampal slice preparation: an electrophysiological and ultrastructural analysis.

The viability and stability of the in vitro rat hippocampal slice preparation were assessed using electrophysiological and electron microscopical means. Slices exhibited lifetimes of 6-19 h. Correlation between the duration of electrical activity and changes in ultrastructure of these slices was found. Possible reasons for the wide variability in lifetime of the hippocampal slice are suggested.

Animals↗

Effects of electrolyte or colloid infusion on the injured lung.

Diffuse lung injury (acid aspiration) and a modest intravascular volume deficit (15% total blood volume) were produced in mongrel dogs. Replacement of lost volume was with shed blood plus an equal volume hydroxy ethyl starch (Group I) or shed blood plus balanced salt solution (3 ml/ml shed blood). Extravascular lung value (EVLW) measurements were used to quantitate edema formation and alveolar arterial oxygen gradient (A-a and O2) was monitored on a reflection of hypoxia. No significant differences were observed in A-a and O2 between groups despite a significantly larger amount of pulmonary edema in Group I (hydroxy ethyl starch).

Animals↗

Efficacy of aerosolized methylprednisolone in an animal model of aspiration pneumonitis.

Methylprednisolone (MPSS, 30 mg/kg) was administered intrabronchially by nebulization 15 min after HCl aspiration in anesthetized dogs. Control animals (SALINE group) received saline nebulization without steroid. Hemodynamic and oxygenation variables were determined before and 1, 2 and 3 hr after aspiration. At autopsy, lungs were removed and desiccated for gravimetric determination of lung water. Three hr postaspiration, intrapulmonary shunting (Qsp/Qt) in the MPSS group was significantly lower (22 vs 41%) and arterial oxygen tension (PaO2) was higher (265 vs 122 torr) than in the SALINE group. Thus, direct application of this glucocorticoid to airway membranes following acid aspiration improved gas exchange without obvious benefit to edema formation or cardiac output.

Aerosols↗

Indomethacin pretreatment in continuous positive-pressure ventilation.

The purpose of the study was to investigate the possible involvement of prostaglandins (PG) and thromboxanes (TX) in the cardiovascular and pulmonary changes associated with the use of continuous positive-pressure ventilation (CPPV). Indomethacin (IND), an inhibitor of PG cyclo-oxygenase, was used to block the synthesis and release of PG and TX in the lung after alveolar stretch with CPPV. Groups of dogs received CPPV (buffer group) or CPPV + IND 5 mg/kh iv (CPPV + IND). Pulmonary edema or alveolar hemorrhage was evident in 5 of 6 buffer animals. This damage was also manifested by a 50% decrease in lung compliance. However, IND appeared to block development of lung tissue damage in 5 of 6 CPPV + IND dogs and compliance remained normal. A 52% lowering of cardiac index (CI) in the buffer group paralleled a 71% reduction of left ventricular dP/dt max (first derivative of left ventricular pressure). Peak transmural right heart filling pressure decreased only 15%. in contrast, the 38% decrement of CI in the CPPV + IND animals was coupled with a 98% reduction in filling pressure, but only a 25% decrease in dP/dt max. CPPV-induced changes may have been related, in part, to the release of cytotoxic negative inotrope(s) from damaged alveolar membranes because IND pretreatment blocked this damage.

Analysis of Variance↗

Amino acid changes in a genetic strain of epileptic beagle dogs.

A neurochemical evaluation of beagle dogs with naturally occurring spontaneous generalized convulsive seizures was performed. Amino acid profiles of serum, cerebrospinal fluid (CSF), and biopsied cerebral cortex from epileptic dogs were compared with those from seizure-free siblings. No differences in absolute levels were noted. However, when levels were normalized as a percent of total free amino acids, seizures was performed. Amino acid profiles of serum, cerebrospinal fluid (CEF), and biopsied cerebral cortex from epileptic dogs were compared with those seizure-free siblings. No differences also the two groups differed in certain respects. Ten significant correlations between amino acid pairs appeared in epileptic dogs, but only one was seen in seizure-free animals. Seven of these ten correlations involved glutamate or taurine. It was noted that the highly correlated amino acids (taurine, glutamate, glycine, glutamine, alanine) all utilize sodium-dependent membrane transport processes. The sum of glutamate, aspartate, and glycine levels (competing sodium-dependent high-affinity systems) was significantly lower in epileptic beagles. Since this difference was noted in serum but not CSF or brain, it may indicate a diminished capacity of sodium-dependent high-affinity renal transport for acidic and certain small neutral amino acids.

Amino Acids↗

[Gamma-aminobutyric acid system and bioelectric activity of the brain of rats during alcoholic intoxication].

The changes of the GABA metabolizing enzyme activities in rat brain are connected with the phases of the functional condition of the central nervous system and doses of ethanol. Increase in the dose of ethanol caused the distinct decrease of locomotion degree and vertical component of motor activity. Chronic ethanol consumption caused an increase of the enzyme activities of GABA metabolism without any change of the brain GABA level. The brain glutamine concentration and the GAbA-T activity were increased but there was no change in the brain GABA level of rats after 24-hr ethanol withdrawal. Significant increases in mean energy content of EEG occurred throughout the withdrawal period in both dietary groups of rats receiving ethanol. In 24 hr after withdrawal, prodromal and ictal activity were apparent in the spontaneous EEG records of "ethanol" group.

4-Aminobutyrate Transaminase↗