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S K Salzman

Publications and source records attributed to S K Salzman.

At least 37 records · Page 2Linked to original sources

Anesthesia influences the outcome from experimental spinal cord injury.

The effect of anesthesia upon the functional outcome after experimental spinal cord injury (SCI) was studied in 221 rats subjected to graded weight drop contusion in the thoracic cord. Neurologic function was assessed in a blinded fashion for one week after injury using a modification of the method of Tarlov. The post-mortem concentrations of serotonin and its metabolite were measured in injured and surrounding spinal tissues in a subset of animals in order to estimate the survival of descending long-tract axons. In initial studies using non-ventilated animals where body temperature was not controlled (n = 130), halothane anesthesia was associated with significantly better neurologic scores at all levels of injury (50, 100 and 250 g.cm) in comparison to pentobarbital. In a second experiment under these conditions (n = 53) the effect of halothane was observed after a 50 g.cm injury in comparison to both pentobarbital and nitrous oxide. Improved neurologic recovery was accompanied by the preservation of normal serotonin and metabolite concentrations in spinal tissue caudal to the site of injury. These values did not differ from those measured in sham-operated animals. Separate experiments (n = 12) revealed halothane's preservation of somatosensory-evoked responses during the early postinjury period in animals showing improved neurologic recovery. Subsequent experiments (n = 12) were performed to assess the effect of oxygen supplementation and the control of rectal temperature and a separate series of acute experiments (n = 14) examined arterial blood pressure responses to injury in halothane- and pentobarbital-anesthetized animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Anti-inflammatory activity of substituted 1,3,4-oxadiazoles.

Various 2-(4-biphenoxymethyl)-5-arylamino-1,3,4-oxadiazoles were synthesized by cyclization of the corresponding 1-(4-biphenoxyacetyl)-4-substituted thiosemicarbazides. These compounds were characterized by their elemental analyses and infrared, mass, and nuclear magnetic resonance spectral data. All substituted thiosemicarbazides (100 mg/kg, ip) and cyclized substituted oxadiazoles (100 mg/kg, ip) possessed anti-inflammatory activity, as reflected by their ability to provide protection against carrageenin-induced edema in the rat paw which ranged from 28 to 68% and 36 to 76%, respectively. Cyclization of the substituted thiosemicarbazides, in general, resulted in an increase in the anti-inflammatory activity of their corresponding substituted oxadiazoles, with the exception of those containing 2,4-dimethyl and 3,4-dimethyl substituents in their molecular structure. Hydrocortisone (10 mg/kg, ip) and oxyphenbutazone (40 mg/kg, ip) were used as the standard reference drugs and these provided 45 and 53% protection, respectively. All compounds (1 mM) possessed antiproteolytic activity and the in vitro inhibition of trypsin-induced hydrolysis of bovine serum albumin ranged from 13 to 75% for substituted thiosemicarbazides and 39 to 70% for substituted oxadiazoles. There was no relationship between the anti-inflammatory activity of substituted thiosemicarbazides and substituted oxadiazoles and their antiproteolytic effectiveness. The low toxicity of these compounds was reflected by their high approximate LD50 values, ranging from 500 to 1000 mg/kg.

Animals↗

Role of dopamine receptors in gastrointestinal motility.

Apomorphine (3.5 and 10 mg/kg, s.c.) and morphine (1.3 and 10 mg/kg, s.c.) produced a dose-dependent decrease in gastrointestinal transit of charcoal dust in rats. The involvement of dopamine in such a constipatory effect was found to be mediated to a greater extent by DA2 than by DA1 receptors, using a specific DA1 antagonist (SCH 23390) and DA2 antagonists (alizapride, domperidone). The decrease in apomorphine (50 micrograms) and dopamine (100 and 200 micrograms)-induced gastrointestinal transit after intracisternal administration was antagonized by haloperidol. These results provide evidence for the involvement of dopamine receptors in the constipatory effects of apomorphine and morphine in rats.

Animals↗

The somatosensory evoked potential predicts neurologic deficits and serotonergic pathochemistry after spinal distraction injury in experimental scoliosis.

The validity of the somatosensory evoked potential as an intraoperative spinal cord monitor was evaluated in an experimental model of scoliosis in the rat and a Harrington distraction model of injury. Under these conditions, it was found that any change in latency or amplitude of the major negative wave above a certain level was a significant predictor of an adverse neurologic outcome. Changes in latency of 4% or greater and changes in amplitude of 50% or greater were unequivocal indicators of spinal cord injury. Postmortem analyses of the spinal neurotransmitter serotonin revealed that apparent false-positive results of the SEP were, in fact, true-positive results.

Animals↗

Experimental scoliosis in the rat. I. Methodology, anatomic features and neurologic characterization.

The purpose of this study was to develop a simple and reproducible model of scoliosis in the rat without producing direct trauma to the spine, in order to both provide a system for the study of human scoliosis and to ultimately study the conditions under which distraction-induced trauma might occur. Right lateral curvatures were produced in three groups of rats (N = 36, 59, 25) at 18-21 days of age by suturing the inferior angle of the scapula to the ipsilateral bony pelvis. In the first group of animals, it was found that a minimum period of 6 weeks of tethering was required in order to produce permanent structural curvatures after release of the tethering sutures. In the second group of rats, a number of morphologic and histologic changes characteristic of human scoliosis were noted, including apical wedging, deviation of the apical spinous process, pelvic asymmetry, rib hump deformity, vertebral rotation, displacement of the nucleus pulposus, disorganized columnization of disc cartilage cells, and an increased number of Type I muscle fibers in paravertebral muscle on the convex side of the curve. Finally, in the third group of rats, a mild spasticity was seen in the ipsilateral hindlimb in approximately one-third of the animals with curvatures greater than 40 degrees. This spasticity was not associated with a change of latency or amplitude of the somatosensory-evoked potential (SSEP). Each curvature group displayed SSEP characteristics that were not statistically different from unoperated control animals. These results indicate the validity of this model system for the study of scoliosis, and, in particular, its usefulness for the study of operative-induced trauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Experimental scoliosis in the rat. II. Biomechanical analysis of the forces during Harrington distraction.

The purpose of this study was to characterize the forces resulting from Harrington distraction of the spine in an experimental model of scoliosis in the rat, in order to establish both the similarity of this model to human scoliosis and identify potential force parameters that may be useful for clinical decision-making. Harrington distraction was performed in 36 rats that had been made scoliotic 9-12 weeks earlier by the method described in the previous paper. Distractions were carried out in discrete and timed steps until separation of the vertebral laminae (mechanical failure) occurred at the upper hook site. Distractive forces were monitored continuously by a strain gauge mounted on the tension side of the upper arm of the outrigger. The resulting data were compared among the various curvature groups. The relationship between the length of distraction and the maximum force produced was similar for all animals regardless of curvature. This relationship was quadratic and was characterized by an inflection point where forces increased rapidly with each distraction. The amount of distraction necessary to reach both the inflection and failure points differed only for curves above 100 degrees. The amount of force required to reach failure was lower for curves above 75 degrees. Curves above 50 degrees had a lower percent correction at the inflection point. Bending and tensile forces were calculated by vector analysis. Axial load efficiencies were greater for curves above 50 degrees, as evidenced by increased bending forces in these animals. The viscoelasticity of the spine decreased after inflection in all animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prolongation of hibernation bout duration by continuous intracerebroventricular infusion of melatonin in hibernating ground squirrels.

Melatonin was infused intracerebroventricularly into hibernating golden-mantled ground squirrels (Citellus lateralis) maintained at 5 degrees C in darkness. Continuous infusion at a rate of 0.5 microliter/h was accomplished using an osmotic minipump. The effect of melatonin on hibernation bout duration was determined with reference to the natural trend in bout duration for each animal. At doses of 200 and 400 ng/h, melatonin produced a dose-related increase in bout duration. No effect was observed following control infusions of artificial cerebrospinal fluid or lower doses of melatonin.

Animals↗

Treatment of experimental spinal trauma with thyrotropin-releasing hormone: central serotonergic and vascular mechanisms of action.

The sites and mechanisms by which thyrotropin-releasing hormone (TRH) may ameliorate the effects of spinal cord contusion were studied in the rabbit. We have examined the actions of an effective intravenous TRH infusion on the spinal content and utilization of the monoamine neurotransmitters (norepinephrine [NE], dopamine [DA], and serotonin [5-HT]) in both control and injured animals. The ability of TRH to penetrate the blood-brain barrier was determined by the measurement of spinal cord TRH immunoreactivity and the effect of TRH upon the development of traumatic edema was evaluated. TRH was found to enter the spinal cord to a large extent in approximately half the animals, but to a lesser degree in the remainder. This indicates the potential for a central site of action. In this regard, TRH induced a significant increase in the metabolism or utilization of 5-HT above the injury site. This effect was not observed in control animals. Finally, TRH was able to cancel the formation of edema at the injury site. These results are correlated with previously described mechanisms and are discussed in terms of the co-existence of TRH and 5-HT in raphe-spinal neurons descending from the medulla.

Animals↗

Monoaminergic responses to spinal trauma. Participation of serotonin in posttraumatic progression of neural damage.

The monoamines norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and their major metabolites were measured in the spinal cord of rabbits following laminectomy or impact injury to the thoracic cord. Samples were taken 30 minutes, 60 minutes, 4 hours, and 6 weeks after injury. Utilization ratios (metabolite/transmitter) were calculated from the data. Turnover rates for NE and DA were also calculated at 30 minutes using the alpha-methylparatyrosine method. Trauma resulted in rapid and sustained elevations in 5-HT concentration at and around the injury site. The catecholamines were depleted slightly at the injury site. Levels of 5-hydroxyindole-3-acetic acid were elevated at 30 minutes but fell to baseline by 4 hours, resulting in a decrease in the 5-HT utilization ratio. The utilization and turnover of NE was increased at the injury site, while DA function was not affected. The large short-term increase in 5-HT levels may have been due to extravasation of platelet 5-HT stores into spinal tissue, rather than due to changes in neuronal 5-HT metabolism. At 6 weeks after injury, each monoamine and metabolite appeared to accumulate in spinal cord tissue proximal to the insult. Distal to the injury, depleted amine stores displayed augmented utilization. The data are discussed in terms of a serotonergic hypothesis of the progression of neural damage after trauma, with the interaction of 5-HT with raphe-spinal nerve terminals as a principal event.

Animals↗

Effects of halothane on intraoperative scalp-recorded somatosensory evoked potentials to posterior tibial nerve stimulation in man.

Somatosensory evoked potentials (SEPs) were monitored in 116 patients receiving halothane anesthesia during spinal fusion surgery. Whereas it has been generally assumed that the use of halogenated inhalational anesthetics should be avoided with SEP monitoring because of their purported deleterious effects on scalp-recorded sensory responses, we found that reproducible SEPs were obtained throughout the surgical procedure in 91% of the cases we monitored while using halothane at concentrations of 0.25-2.0%. In those cases in which halothane was delivered continuously at 0.5%, reproducible evoked responses were recorded in 96% (75 of 78) of the patients. Our data demonstrated 3 major effects of halothane on the SEP: (a) a small but significant decrease in the average amplitude of the first two components (N25 and P30), (b) a significant increase in the average latency of the late positive component (P53) of the wave form, and (c) occasional obliteration of components N25, N40, P53, and N71, but never of P30. These effects did not, in most cases, interfere with our ability to obtain clinically useful recordings. Our results suggest that in many instances the use of halothane anesthesia can be combined successfully with the recording of intraoperative SEPs.

Electric Stimulation↗

Determination of intraoperative plasma catecholamine concentrations using liquid chromatography with electrochemical detection.

Liquid chromatography with electrochemical detection was used for the determination of norepinephrine and epinephrine in human plasma samples obtained prior to, after, and six times during the course of spinal fusion surgery for the correction of scoliosis. The catecholamines were extracted from plasma by alumina adsorption and chromatographed isocratically using a reversed-phase, ion-pairing system. Data obtained are compared to those obtained intraoperatively by other authors using a radioenzymatic method, and the mechanism of sympathetic activation during surgery is discussed. Preliminary data using 3-micron particle size columns and dual-parallel electrochemical detection are presented.

Adolescent↗

In vivo analysis of dopamine and its metabolites in the caudate nucleus during euthermia and hibernation.

Golden-mantled ground squirrels (Citellus lateralis) were chronically implanted with a unilateral push-pull cannula in the caudate nucleus. Perfusates obtained in these unanesthetized, unrestrained animals during the euthermic (non-hibernating) and hibernating states were analyzed for dopamine (DA) and its metabolites (homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methoxy-4-hydroxyphenethanol (MOPET) using high performance liquid chromatography with electrochemical detection. The data revealed clear differences in the performance of the caudate DA system in the two states. During the euthermic state, DA metabolism was indicative of a constant and high turnover rate. Free DA was not detectable in the majority of samples, HVA was detected at consistently high levels, and DOPAC and conjugated DA were present at low levels. By contrast, DA metabolism was sharply altered during hibernation. Free DA was present at high concentrations and HVA concentrations were low. DOPAC was not detected in any sample whereas MOPET was present in all samples. Conjugated DA was present at high concentrations during the second half of the hibernation bout. The shift in the post-release disposition of DA could enhance the stability of DA receptors (i.e. prevent supersensitivity) during the prolonged periods of reduced neural activity typical of hibernation.

3,4-Dihydroxyphenylacetic Acid↗

Determination of norepinephrine in brain perfusates using high-performance liquid chromatography with electrochemical detection.

A procedure for determining catecholamine levels in brain perfusates is described. A single-step extraction on alumina followed by reversed-phase ion-pair chromatography and electrochemical detection was employed. Levels of norepinephrine are reported in push-pull perfusates of the rat hypothalamus under baseline and various ion substitution conditions. The resulting estimated norepinephrine release values are correlated with the behavior of the animal. The data are discussed in terms of the validity of the measures and the noradrenergic mediation of behavior.

Animals↗

Inhibition of evoked dopamine release by monopropionylcadaverine in vitro.

A naturally occurring diamine, cadaverine, and one of its acyl derivatives, monopropionylcadaverine, were tested for their effects on the in vitro release of endogenous dopamine from slices of the rat neostriatum. Dopamine release was allowed to occur spontaneously and was evoked by elevating the potassium concentration in the incubation medium or by electric field stimulation. Monopropionylcadaverine had no effect on spontaneous release of dopamine and little effect on potassium-evoked release of dopamine, but at concentrations as low as 10(-8) M in the medium it significantly depressed the electrically induced dopamine release.

Animals↗

Effects of thyrotropin releasing hormone on hypothalamic thermosensitive neurons of the rat.

The actions of thyrotropin releasing hormone (TRH) were tested on the firing rat of temperature-sensitive and temperature-insensitive neurons in the rat preoptic/anterior area of the hypothalamus (POA). Iontophoretic application of TRH resulted in inhibition of the firing rate of temperature-insensitive, warm-sensitive and cold-sensitive neurons. The inhibitory response of cold sensitive neurons in TRH was relatively mild, however, and 2 of 6 of these neurons inhibited by TRH also displayed rebound increases in discharge rate following cessation of TRH application. These results parallel the hyperthermic effects of microinjected TRH and lend further support of the hypothesis that TRH acts as a neurotransmitter or neuromodulator in the POA portion of the CNS thermoregulatory network.

Animals↗

Cadaverine in the rat brain: regional distribution and acylation of [14C]cadaverine in vivo and uptake in vitro.

The regional distribution and acylation of intraventricularly injected [14C]cadaverine was studied in the rat brain over a 48-h period. The concentrations of labeled cadaverine and its acyl derivatives, N-monoacetylcadaverine and N-monopropionylcadaverine, were determined in the telencephalon, striatum, hypothalamus, midbrain, cerebellum, and medulla-pons by TLC of their 5-dimethylamino-1-naphthalenesulfonyl derivatives, followed by liquid scintillation spectrometry. The apparent passage of radioactivity from the ventricular space into brain tissue was slow, with the concentrations reaching a peak at 24 h after injection. The percentage of radioactivity in the acyl forms of cadaverine, however, was maximal 4 h after injection, with the propionyl form predominating. The telencephalon, striatum, and hypothalamus contained the highest concentrations of radioactivity, in all three forms, at all elapsed times. A high-affinity uptake mechanism for cadaverine was demonstrated in slices of these tissues. This process was completely inhibited by equimolar concentrations of unlabeled putrescine.

Acylation↗