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PubMed1992

Spinal cord protection with intravenous nimodipine. A functional and morphologic evaluation.

The purpose of this study is to determine the effects of ischemia in the spinal cord when a calcium channel blocker, nimodipine, is administered intravenously before, during, and after crossclamping of the thoracic aorta. In this series of experiments, 18 pigs underwent thoracotomies and had 17.5 to 18.0 cm of the thoracic aorta clamped for 30 minutes. By random selection, nine animals received intravenous nimodipine (2 micrograms/kg per minute) and nine control animals received only a carrier solution. Of the nine animals that received nimodipine, eight walked after the operation. In contrast, in the control group only two of nine animals walked. The ninth nimodipine-treated animals walked but had a severe delayed deterioration response. All animals, except one control animal, had a negative central spinal perfusion pressure. Morphologic examination of serial sections of spinal cords from control animals showed diffuse neuronal necrosis. In comparison, cords from the nimodipine group had swollen neurons accompanied by an inflammatory infiltrate and only occasional necrotic neurons. With this data, we conclude that certain calcium channel blockers, when administered in sufficient doses, can lend a protective effect to the spinal cord during ischemic events even when cord perfusion pressure has dropped to dangerously low levels.

Animals↗
PubMed1976

Ethanol effects on muscle spindle afferent activity and spinal reflexes.

The effects of ethanol on muscle spindle afferent activity and on the mono- and polysynaptic reflexes were examined in cats. Ethanol was administered incrementally as intravenous infusions of 0.7 g/kg of ethanol 30 minutes apart; mean arterial blood alcohol concentrations reached 30 minutes after the first and fourth infusions were 1.1 and 3.8 mg/ml, respectively. Ethanol produced modest, dose-related increases in the afferent activity from muscle spindles in spinal- and pentobarbital-anesthetized cats. Mean phasic and static discharge frequencies were both increased approximately 10 impulses/sec after infusions of a total of 2.8 g/kg. In unanesthetized animals, comparable blood levels of ethanol were associated with mild to marked motor incoordination. The mean amplitudes of the mono- and polysnaptic reflexes in spinal animals, elicited with supramaximal single shocks to the muscle nerve, were depressed to 92 and 84% of control levels, respectively, after 0.7 g/kg and continued to fall to 50 and 60% of control levels after 2.8 g/kg of ethanol. Ethanol failed to depress preferentially polysynaptic reflexes. It is concluded that the spindle afferent excitation was involved in the motor effects of ethanol but that it was insufficient to explain fully the skeletomotor alterations produced by ethanol; rather, ethanol actions at peripheral and spinal and, perhaps, supraspinal sites all appear to be involved in ethanol-induced impairment of motor function.

Achilles Tendon↗
PubMed2006

Acute spinal cord ischemia during aortography treated with intravenous thrombolytic therapy.

Acute anterior spinal cord ischemia is a rare but disastrous complication of endovascular aortic procedures. Although intravenous thrombolysis with recombinant tissue plasminogen activator is an effective treatment for acute brain ischemia, its use for the treatment of spinal cord ischemia has not previously been reported. We report the case of a patient who developed anterior spinal cord ischemia during diagnostic aortography He was treated with intravenous recombinant tissue plasminogen activator within 3 hours after the onset of symptoms. The patient had a rapid neurologic improvement and was discharged from the hospital 3 days after thrombolysis, regaining his ability to walk unassisted. We propose that acute spinal cord ischemia can be treated with intravenous recombinant tissue plasminogen activator within 3 hours after the onset of symptoms, as can any other case of acute ischemic stroke.

Acute Disease↗
PubMed2004

A soluble Nogo receptor differentially affects plasticity of spinally projecting axons.

In the central nervous system, regeneration of injured axons and sprouting of intact axons are suppressed by myelin-derived molecules that bind to the Nogo receptor (NgR). We used a soluble form of the NgR (sNgR), constructed as an IgG of the human NgR extracellular domain, to manipulate plasticity of uninjured primary afferent and descending monoaminergic projections to the rat spinal cord following dorsal rhizotomy. Rats with quadruple dorsal rhizotomies were treated with intrathecal sNgR or saline, or were left untreated for 2 weeks. Rhizotomy alone resulted in sprouting of serotonergic axons and to a lesser extent, tyrosine-hydroxylase (TH)-expressing axons, while axons expressing dopamine-beta-hydroxylase (DbetaH) were unaffected. Human IgG immunohistochemistry revealed that sNgR infused into the intrathecal space penetrated approximately 300 microm into spinal white and grey matter. Separate axonal populations differed in their responses to intrathecal sNgR: TH-expressing and DbetaH-expressing axons responded most and least vigorously, respectively. Serotonergic axons were identified by serotonin (5-HT) or serotonin transporter (SERT) immunohistochemistry. Interestingly, a large increase in 5-HT compared to SERT-positive axons density in both saline and sNgR-treated rats indicated that serotonergic axons both sprouted and increased their transmitter content in response to rhizotomy and sNgR treatment. Calcitonin gene-related peptide-positive axons were largely depleted ipsilaterally by rhizotomy, and sNgR increased axon density only in deeper contralateral laminae (III-V). GAP-43 immunohistochemistry revealed a small increase in axon density following dorsal rhizotomy that was further augmented by sNgR treatment. These results reveal a differential effect of myelin antagonism on distinct populations of spinally projecting axons.

Animals↗
PubMed1989

Use of intrathecal baclofen administered by programmable infusion pumps in resistent spasticity.

On the basis of previous experimental and clinical studies patients with severe spasticity due to spinal cord damage from multiple sclerosis in 8 cases and postraumatic paraplegia in 6 and resistent to all conservative treatments were selected for a trial with morphine and baclofen administered intrathecally through a catheter placed in the spinal subarachnoid space rostral to the affected segments and attached to a subcutaneous reservoir. Whereas morphine single injection did not show any benefit, baclofen bolus injection 30 to 60 micrograms, revealed a marked decrease of spasticity and associated symptoms in 8 cases. After checking the clinical effect during 3 weeks and changes in electroneurophysiological studies and bladder manometry the catheter was attached to a subcutaneous programmable pump able to be refilled percutaneously and administered baclofen continuously or more often following a multistep complex programme in total doses of 90 to 150 micrograms per day. After a mean follow-up of 5 months all cases showed an absence of spasms and pain, a notable improvement for bettering of sphincter functions and a marked muscle relaxation that improves motor capacity, leading to increased ambulation or mobility. Neither complications nor side-effects were observed.

Adult↗
PubMed2004

Spinal cord lesion after long-term intrathecal clonidine and bupivacaine treatment for the management of intractable pain.

Long-term intrathecal drug administration using implanted pumps is increasingly used in the treatment of chronic refractory pain [Anderson and Burchiel 1999, Neurosurgery 44 (1999) 289; Krames 2002, Best Pract Res Clin Anaesthesiol 16 (2002) 619; Wallace 2002, Neurology 59 (2002) S18]. Extensive clinical experience over the last 15 years suggests that in selected cases the technique is safe, although infections, system malfunction and drug-related complications have been reported. In most cases, drug-related spinal cord injuries have resulted from the compression of a spinal inflammatory mass or abcess rather than from a direct neurotoxic effect. We report on a case of toxic spinal cord lesion occurring after more than 3 years of uneventful continuous infusion of a mixture of bupivacaine and clonidine.

Analgesia, Epidural↗
PubMed2005

Targeted retrograde gene delivery into the injured cervical spinal cord using recombinant adenovirus vector.

Direct routes of gene administration (intrathecal, intracerebroventricular or intraparenchymal infusion) have been used for effective and sustained gene delivery, but serious concerns exist about possible traumatic injury as well as neural damage that may lead to further tissue necrosis, apoptosis and cell death. We evaluated targeted retrograde gene delivery through the sternomastoid muscle (innervated by the spinal accessory nerves) into the injured cervical spinal cord using a recombinant adenovirus vector. LacZ gene expression in the cervical spinal cord was noted from 3 days to 4 weeks after the injection of vector into the sternomastoid muscles of the rats. Recombinant adenovirus vector was transferred via a retrograde mechanism into the injured cervical spinal cord with high transduction efficacy (80.6--98.9%) over certain adenoviral titer and dosage. Transduction was less efficient when the vector was injected 1 and 2 weeks after spinal cord injury (44.2--56.8%). Our results indicate retrograde delivery of recombinant adenovirus vector is possible immediately after spinal cord injury, and that this method is promising for gene delivery because it is effective, selective, less invasive to the injured spinal cord, has long-lasting gene expression, and is potentially feasible treatment choice for spinal cord injury.

Adenoviridae↗
PubMed1990

Chronic intrathecal baclofen administration for control of severe spasticity.

Baclofen, the most effective drug for treating spasticity, is a specific agonist of gamma-aminobutyric acid-B receptors, and is very abundant in the superficial layers of the spinal cord. Given orally, baclofen does not easily penetrate the blood-brain barrier, and is distributed equally to the brain and spinal cord. Direct intrathecal administration was given in order to change the distribution of the drug by preferentially perfusing the spinal cord. Eighteen patients presenting a severe spastic syndrome were treated with chronic intrathecal infusion of baclofen in the lumbar cerebrospinal fluid. After clinical preselection, 38 patients were implanted with a lumbar access port allowing long-term trials in order to determine the efficacy of baclofen therapy and the effective 12-hour dose. The 18 patients selected for chronic administration were implanted with a programmable pump. The pathology in these cases was: multiple sclerosis (6 cases), posttrauma spastic syndrome (eight cases), and (one case each) cerebral palsy, ischemic cerebral lesion, spinal ischemia, and transverse myelitis. The mean follow-up period was 18 months (range 4 to 43 months). The clinical results were evaluated according to muscular hypertony on Ashworth's scale (changed for occurrence of painful spasms) and functional improvement. Results were better for spastic syndrome secondary to traumatic medullary lesion than for demyelinating disease. Hypertonia was improved in all cases as confirmed by the registration of the Hoffman (H) reflex. Painful muscular spasms disappeared in 14 of the 16 affected patients. Significant functional improvement was noted in nine patients and was considerable in three. The risk of side effects secondary to overdose (such as excessive hypotonia or central depression) and the absence of a specific baclofen antagonist stresses the necessity for accurate determination of the efficient dose. After an initial titration period and adjustment of the therapeutic dose, the individual doses were from 21 to 500 micrograms/24 hrs (mean 160 micrograms/24 hrs). This new conservative method is very effective, perfectly reversible, and safe when administered in conditions favorable to its use.

Baclofen↗
PubMed1979

Use of metrizamide computerized tomographic cisternography in the evaluation of patients with malignant glioma for immunotherapy.

The communication between the subarachnoid space and the surgically created tumor cavity in glioma patients was evaluated by metrizamide cisternography. It was necessary to know the presence or absence of such a communication to determine the route of administration of autologous lymphocytes as a form of immunotherapy. The contrast injections were made either into the spinal subarachnoid space or directly into the tumor cavity. The presence of communication was demonstrated and followed by computerized tomographic (CT) scanning. The results were also corroborated by comparing the white cell counts in the fluid from the tumor cavity and the spinal subarachnoid space 24 hours after autologous lymphoid cell infusion. In only two of seven patients was a communication present. In the five patients without a communication, the blocks were at the tentorial hiatus (one patient), due to a nonpatent subarachnoid space over the cerebral convexity (two patients), and the result of adhesions at the pial margin of the tumor cavity (three patients). In addition, certain limitations in the use of computerized tomography in the evaluation of glioma patients are demonstrated. These problems include the effects of steroids on tumor size, the poor correlation between "enhancement" on CT scan and tumor recurrence, and the difficulty of differentiating metrizamide and hemorrhage by CT scan in the immediate postoperative period. (Neurosurgery, 5: 576--582, 1979).

Adult↗
PubMed1997

Intracarotid glucose selectively increases Fos-like immunoreactivity in paraventricular, ventromedial and dorsomedial nuclei neurons.

Perfusion of the forebrain with glucose at concentrations which alter neither plasma insulin nor glucose levels leads to sympathetic activation in some rats. We used the expression of Fos-like immunoreactivity (FLI) as an index of neuronal activation to examine the anatomic substrate underlying this phenomenon. Male Sprague-Dawley rats were infused via the right internal carotid artery with glucose (4 mg/kg/min) or equiosmolar mannitol for 60 min. They were killed 3 h after infusion onset and their brains reacted for FLI. As compared to mannitol-infused controls, 105% and 117% more neurons in hypothalamic ventromedial nucleus (VMN) and parvocellular portion of the paraventricular nuclei (PVN) of glucose-infused rats showed FLI, respectively. Importantly, only about half the glucose-infused rats showed increased FLI cells in these areas when compared to controls. In these same animals, glucose also significantly activated cells in the dorsomedial n. There was little FLI expressed in the magnocellular neurons of the PVN. This selective glucose response was bilateral in keeping with the bilateral distribution of India ink to midline hypothalamic structures following unilateral carotid infusions. Retrograde transport of cholera toxin B from medullary and thoracic spinal cord sympathetic outflow areas showed labeling of about 10% of PVN neurons with FLI activated by intracarotid glucose. There was no double labeling of VMN neurons. This supports the presence of anatomic pathways by which a subpopulation of glucose responsive PVN neurons might activate the sympathetic outflow areas in the medulla and spinal cord. The apparent bimodal distribution of glucose-induced activation of VMN and PVN neurons is in keeping with a similar bimodal pattern of sympathetic activation which obesity-prone but not obesity-resistant rats show following glucose infusions. Taken together, these data support a role for glucose-sensitive VMN and parvocellular PVN neurons in the weight gain phenotype specific sympathetic activation to glucose.

Animals↗
PubMedDate not supplied

Continuous versus single-injection lumbar plexus blocks: comparison of the effects on morphine use and early recovery after total knee arthroplasty.

BACKGROUND AND OBJECTIVES: Continuous lumbar plexus infusion of local anesthetic after total knee arthroplasty has been shown to improve analgesia and early recovery as compared with patient-controlled analgesia (PCA) morphine. Any benefit of an infusion over a single-injection lumbar plexus block has not been directly shown however. METHODS: In a double-blind, randomized, controlled trial, 32 patients undergoing total knee arthroplasty were randomly allocated to 1 of 2 groups: 0.1% levobupivacaine infusion or saline infusion. Preoperatively, all patients received a lumbar plexus block with 25 mL 0.5% levobupivacaine using a posterior approach with a catheter left in situ, a sciatic nerve block with 15 mL 0.5% levobupivacaine, and a spinal anesthetic. At the end of surgery, 0.1% levobupivacaine or saline was infused into the catheter at 10 mL/h for 48 hours. All patients also received PCA morphine. The primary endpoint was morphine use from the PCA machine. Secondary endpoints included pain scores, day of first postoperative mobilization, and nausea. RESULTS: Patients receiving the levobupivacaine infusion used significantly less morphine than those receiving saline (19 mg [interquartile range (IQR) 8.5-29.5] vs 32 mg [IQR 23.5-53.0], P = .04) and also mobilized earlier postoperatively (day 1 or 2 [levobupivacaine] vs day 2 or 3 [saline], P = .001). Pain scores were similar. CONCLUSION: Postoperative infusion of local anesthetic around the lumbar plexus reduces morphine requirement and improves early recovery after total knee arthroplasty as compared with a single-injection block.

Aged↗
PubMed1983

Adverse reactions to dextran in Sweden 1970-1979.

In a retrospective investigation of the period 1970-1979, 478 reports on cases of dextran-induced anaphylactoid/anaphylactic reactions (DIAR) were found. In 458 of these dextran was judged to be the causative agent. The number of units of dextran 40 and 70 used during this decade was 313 598 and 1 051 668, respectively. During the last five years, when reporting of severe adverse drug reactions was mandatory, the incidence of severe DIAR per unit administered was 0.013% for dextran 40 and 0.025% for dextran 70. The incidence of fatal DIAR was 0.003% and 0.004%, respectively. We found a male: female ratio of 1.5: 1 for all DIAR while for the most severe DIAR this ratio was 3: 1. The mean age of the patients was higher in severe than in mild DIAR. Allergic disease did not predispose for severe DIAR. Diabetes, cardiovascular and pulmonary diseases and chronic inflammation were more frequent among the patients who had suffered the most severe DIAR. 22 reactions were characterized by fever and/or shivering, and in 19 of these cases the reaction occurred after infusion of more than one unit of dextran. Severe DIAR occur after infusion of a few ml of dextran. Fatal DIAR during anaesthesia occurred almost exclusively in patients under spinal or epidural blockade. A favourable outcome of resuscitation in DIAR with cardiac arrest was possibly promoted by the infusion of large amounts of crystalloid fluids. We could not show that therapy with steroids, epinephrine or isoprenaline influenced the outcome. Fatal DIAR occurred even after infusion of only 0.5-1 ml of dextran, and we strongly advise against the use of "biological test-doses".

Aged↗
PubMed1995

Acute and late neurotoxicity in the rat spinal cord in vivo induced by glutamate receptor agonists.

We investigated glutamate receptor-mediated neurotoxicity in vivo by means of infusing three specific agonists for non-NMDA receptors (acromelic acid A (ACRO), kainic acid and 1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)) into the adult rat spinal subarachnoid space. ACRO induced long-lasting pure motor, rigid-spastic paraparesis in a dose-dependent manner (EC50: 220 pmol/h) that was accompanied by selective degeneration of spinal interneurons; leaving large anterior horn cells intact. Kainate and AMPA induced paraplegia but with relatively non-selective neuronal damage when given in doses more than 40-fold larger than those required for ACRO. When AMPA (> 100 nmol/h) was infused continuously using a mini-osmotic pump for more than 2 days, rats displayed progressive changes in motor behavior due to extensive damage in the caudal spinal cord where small neurons in the dorsal horns were the most vulnerable. Co-administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) specifically prevented neurotoxicity, suggesting a non-NMDA receptor-mediated mechanism. These results indicate that the non-NMDA receptor is heterogeneous, mediating neuronal damage with different selectivity. It is also suggested that chronic activation of glutamate receptors is capable of inducing slowly progressive neuronal death, which suggests relevance to the pathogenesis of ALS.

Animals↗
PubMedDate not supplied

Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine in patients undergoing abdominal hysterectomy during spinal anesthesia.

BACKGROUND AND OBJECTIVES: Postoperative analgesia and antiemetic efficacy after intrathecal neostigmine were investigated in a randomized, double-blind, placebo-controlled trial of 100 patients undergoing abdominal hysterectomy. METHODS: The patients were assigned to one of five groups (n = 20), and received intravenous prior to the spinal block the antiemetic test drug (except propofol) and 0.05 mg/kg midazolam. The control group (group C), the neostigmine group (group N), and the propofol group (group P) received saline as the test drug. The droperidol group (group D) received 0.5 mg intravenous droperidol, and the metoclopramide group (group M) 10 mg intravenous metoclopramide. Group P was single-blinded and had an intravenous continuous propofol infusion (2-4 mg/kg/h) turned on 10 minutes after the spinal injection. The intrathecal drugs administered were 20 mg hyperbaric bupivacaine (0.5%) associated with either 100 microg neostigmine or saline (for group C). Nausea, emetic episodes, and the need for rescue medication were recorded for the first 24 hours postoperative and scored by the Visual Analog Scale (VAS). RESULTS: Time-to-first-rescue medication and rescue medications in 24 hours were similar among the groups (P = .2917 and P = .8780, respectively). Intrathecal 100 microg neostigmine was associated with a high incidence of nausea and vomiting perioperative, leading to a high consumption of antiemetics (P < .002). None of the antiemetic test drugs were effective in preventing nausea and vomiting after 100 microg neostigmine. CONCLUSIONS: Intrathecal neostigmine (100 microg) was ineffective for postoperative analgesia after abdominal hysterectomy due to side effects of nausea and vomiting.

Anesthesia, Spinal↗
PubMed1995

Intrathecal injection of an oxytocin-receptor antagonist attenuated postnephrectomy natriuresis in the male rat.

We have previously shown that oxytocin (OT) is a major humoral mediator in postnephrectomy natriuresis. As immunoassayable OT has been demonstrated in the spinal cord, the aim of this investigation was to determine whether OT receptors in the spinal cord are also involved in this natriuresis. The experiments were performed on anesthetized male rats. Before acute unilateral nephrectomy, an oxytocin-receptor antagonist was injected intrathecally in the thoracolumbar region in rats. Postnephrectomy natriuresis was attenuated by this injection but not by intrathecal injection of artificial cerebrospinal fluid. Our results suggest that OT receptors within the spinal cord may influence the autonomic nervous regulation of renal function. In an additional experiment, intravenously infused hexamethonium did not prevent the adaptive natriuresis in the remaining kidney. We conclude that OT receptors in the spinal cord are involved in the postnephrectomy natriuresis, possibly as a component in the afferent signal pathway.

Animals↗
PubMedDate not supplied

0.1% bupivacaine does not reduce the requirement for epidural fentanyl infusion after major abdominal surgery.

BACKGROUND AND OBJECTIVES: Although local anesthesia has been demonstrated to potentiate spinal morphine analgesia in animal studies, results comparing epidural local anesthesia/opioid mixtures with opioid alone are contradictory in clinical studies. The hypothesis was that, although the concentration of bupivacaine (0.1%) was low to minimize its adverse effects, if the infusion rate of a fentanyl/bupivacaine solution was closely adjusted according to need, the presence bupivacaine would reduce the requirement for epidural fentanyl. METHODS: Forty patients were randomly assigned to receive either fentanyl (10 micrograms/mL) or a fentanyl/bupivacaine (0.1%) mixture epidurally corresponding to the dermatome of the surgical incision in a double-blind fashion for the first 18 hours after major abdominal surgery. The infusion was titrated for each patient to the rate required for pain relief during forced inspiration (pain score < or = 2, maximum 10). Pain scores, the fentanyl doses required, plasma concentrations of fentanyl at 18 hours, and the incidence and severity of adverse effects were recorded. RESULTS: Patients reported similar median pain scores and were equally satisfied with pain relief in both groups. The mean required post-operative fentanyl infusion rate (57.7 +/- 19.5 micrograms/h) and the plasma concentrations (0.84 +/- 0.36 ng/mL) in the fentanyl group were comparable to the infusion rate (54.4 +/- 19.2 micrograms/h) and the plasma concentrations (0.86 +/- 0.36 ng/mL) in the fentanyl/bupivacaine group. Respiratory and cardiovascular functions were preserved, and the incidence of nausea, pruritus, and periods of drowsiness or sleep were similar in both groups. CONCLUSIONS: In low concentrations (0.1%), bupivacaine did not reduce the titrated dose of epidural fentanyl required for adequate pain relief during forced inspiration after major abdominal surgery. The incidence and severity of adverse effects were also comparable whether or not low-dose bupivacaine infusion was used.

Abdomen↗
PubMed2000

[Negative-pressure pulmonary edema associated with transurethral resection syndrome].

We described a patient who had developed negative-pressure pulmonary edema associated with severe transurethral resection syndrome. A relatively healthy, 67-yr-old man (171 cm and 77 kg) with hypertrophic prostate was scheduled for transurethral resection of the prostate under spinal anesthesia. The patient was sedated with continuous propofol infusion because of his anxiety and wish of being asleep. Fifty minutes after starting the operation, electrolyte analysis revealed a decrease in serum Na+ concentration (116 mEq.l-1), and 10 mg of furosemide and hypertonic saline were administered. Thirty minutes later, the arterial oxygen saturation dropped suddenly and arterial blood gas analysis suggested marked pulmonary insufficiency (PaO2: 64 mmHg and PaCO2: 59.4 mmHg). The patient's trachea was intubated and endotracheal release of pinkish foamy sputum was observed. Chest X-ray showed severe lung edema. Massive absorption of the irrigation fluid might have decreased the electrolyte concentration (Na+: 101.0 mEq.l-1) and colloid oncotic pressure. No evidence of cardiac failure was observed immediately after the incidence of pulmonary edema with pulmonary catheter monitoring. The patient's airway was almost intact under spontaneous breathing, but augmented negative-pressure derived from intermittent snoring was considered to be sufficient to break hydrostatic balance of pulmonary capillary vessels and lead to severe pulmonary edema.

Aged↗