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PubMed2006

[Comparison of prophylactic infusion of ephedrine and phenylephrine during Cesarean section under spinal anaesthesia].

Spinal anaesthesia for caesarean delivery may be associated with hypotension and fetal acidosis. Prophylactic infusion of phenylephrine (PE) immediately after the induction of anaesthesia appears to be a more effective approach than administration of ephedrine to reduce the incidence, frequency and severity of hypotension. Furthermore, PE appears to be associated with better fetal acid-base status than is ephedrine.

Acidosis↗
PubMed2002

Cold blood spinal cord plegia for prediction of spinal cord ischemia during thoracoabdominal aneurysm repair.

BACKGROUND: This clinical study was undertaken to evaluate changes in motor evoked potentials (MEPs) during cold blood infusion into a thoracoabdominal aortic aneurysm. We also determined the efficacy of this infusion method for predicting spinal cord injury during thoracoabdominal aortic aneurysmal surgery. METHODS: We monitored descending evoked spinal cord potentials (ESCPs), segmental ESCPs, and MEPs during the prosthetic replacement phase of thoracoabdominal aneurysmal surgery. We perfused cold blood (4 degrees C, 300 to 450 mL) into aneurysms after clamping the aorta, while monitoring spinal cord potentials in 6 cases of thoracoabdominal aortic aneurysm. If the spinal cord potentials decreased during infusion of cold blood, we reconstructed the intercostal arteries in the aneurysm. If the potentials did not change during the infusion of cold blood and after the aneurysmectomy, we did not reconstruct the intercostal arteries and ligated all of them. RESULTS: Postoperative paraplegia did not occur in any case. The MEPs decreased in amplitude after infusion of cold blood in 3 cases, but amplitude recovered after reconstruction of the intercostal arteries. The other 3 cases did not show any change after infusion of cold blood, and all of the intercostal arteries in the aneurysm were ligated. CONCLUSIONS: Cold blood infusion into the aneurysm while monitoring MEPs was a useful adjunct to detect the presence of critical intercostal arteries and to facilitate thoracoabdominal aortic aneurysmal surgery.

Aged↗
PubMed1997

Concentration-dependent changes in motor behavior produced by continuous intrathecal infusion of excitatory amino acids in the rat spinal cord.

A growing body of evidence has suggested that glutamate receptors mediate selective degeneration of neurons in the central nervous system during the development of neurodegenerative diseases. Glutamate receptors are divided into N-methyl-D-aspartate (NMDA)-type and non-NMDA-type. Neurotoxicity mediated by the latter has attracted much interest as a possible causative mechanism underlying amyotrophic lateral sclerosis (ALS). As the clinical course of ALS is chronic and progressive, investigation of chronic effects of non-NMDA receptor agonists on neuronal function would be useful for evaluating the role of glutamate receptor-mediated neurotoxicity in ALS. However, chronic non-NMDA receptor-mediated neurotoxicity has been investigated less thoroughly than acute neurotoxicity. We infused an aqueous solution of R,S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) intrathecally and continuously by an osmotic minipump in rats. This method of continuous infusion enabled us to keep the drug concentration relatively constant in the cerebrospinal fluid surrounding the spinal cord. The present method of AMPA administration is more suitable for investigating ALS pathogenesis than acute injections, in view of the gradual progression of the disease and the selectivity of lesions produced.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Expression of c-fos-like immunoreactivity in the feline brainstem in response to isometric muscle contraction and baroreceptor reflex changes in arterial pressure.

This study compared whether activation of muscle ergoreceptor afferents caused by isometric muscle contraction, activation of baroreceptor afferents induced by i.v. infusion of phenylephrine, or baroreceptor afferent inactivation, caused by carotid artery occlusion, elicit similar patterns of c-Fos induction in brainstem areas. Adult cats were anesthetized with alpha-chloralose, and in each case, the experimental intervention caused an increase in the arterial blood pressure. There were two sets of control experiments: in both, animals underwent the same surgical procedures but then either remained at rest for the entire study, or the tibial nerve was stimulated, as in the contraction group, following muscle paralysis with tubocurarine. Following the procedures, animals rested for 90 min to allow neuronal expression of c-Fos. Control cats showed very little c-Fos immunoreactivity (c-Fos-ir) in the brainstem. Muscle contraction induced c-Fos-ir expression mainly in the nucleus tractus solitarius, lateral reticular nucleus, lateral tegmental field, vestibular nucleus, subretrofacial nucleus, spinal trigeminal tract and in a lateral region of the periaqueductal grey (P 0.5-1.0). The majority of the c-Fos-ir was found in brainstem areas contralateral to the contracted muscle. In addition, muscle contraction induced c-Fos-ir in the dorsal horns of spinal segments L6-S1 on the ipsilateral side of the spinal cord. Phenylephrine infusion caused c-Fos-ir expression in the nucleus tractus solitarius, spinal trigeminal tract, solitary tract, and dorsal motor nucleus of the vagus. No c-Fos-ir was apparent in the periaqueductal grey. Carotid occlusions induced c-Fos-ir expression in the area postrema, nucleus tractus solitarius, solitary tract, and spinal trigeminal tract. Expression was bilateral. Areas that exhibited c-Fos-ir correspond to sites previously reported to release various neuropeptides in response to muscle contraction or carotid occlusions. These results indicate that the exercise pressor reflex and baroreflex activate similar, but not completely identical, sites in the brainstem.

Afferent Pathways↗
PubMed1997

Neurological impairment during long-term intrathecal infusion of bupivacaine in cancer patients: a sign of spinal cord compression.

Adequate pain relief in patients with far advanced cancer sometimes requires intrathecal (IT) administration of a combination of opioids and local anesthetics. Tumor progression as well as the IT administration of local anesthetics can lead to neurologic dysfunction during treatment. Five patients showed symptoms of compression of the cauda equina or spinal cord shortly after the start of combined IT administration of morphine and bupivacaine in a dosage usually not associated with neurologic symptoms. Unexpectedly, neurologic evaluation suggested compression of the cauda equina and spinal cord, which was confirmed radiographically. Manifestation of new neurologic symptoms during low dose bupivacaine infusion intrathecally might therefore be an early indicator of space-occupying processes within the spinal canal in cancer patients.

Aged↗
PubMed2003

Direct interstitial infusion of NK1-targeted neurotoxin into the spinal cord: a computational model.

Convection-enhanced delivery of substance P (SP) nocitoxins to the spinal cord interstitium is under consideration for the treatment of chronic pain. To characterize treatment protocols, a three-dimensional finite-element model of infusion into the human dorsal column was developed to predict the distribution of SP-diphtheria toxin fusion protein (SP-DT') within normal and target tissue. The model incorporated anisotropic convective and diffusive transport through the interstitial space, hydrolysis by peptidases, and intracellular trafficking. For constant SP-DT' infusion (0.1 microl/min), the distribution of cytotoxicity in NK1 receptor-expressing neurons was predicted to reach an asymptotic limit at 6-8 h in the transverse direction at the level of the infusion cannula tip ( approximately 60% ablation of target neurons in lamina I/II). Computations revealed that SP-DT' treatment was favored by a stable SP analog (half-life approximately 60 min), high infusate concentration (385 nM), and careful catheter placement (adjacent to target lamina I/II). Sensitivity of cytotoxic regions to NK1 receptor density and white matter protease activity was also established. These data suggest that intraparenchymal infusions can be useful for treatment of localized chronic pain.

Chronic Disease↗
PubMed2004

Perispinal analgesia for labour followed by patient-controlled infusion with bupivacaine and sufentanil: combined spinal-epidural vs. epidural analgesia alone.

BACKGROUND AND OBJECTIVE: Combined spinal-epidural is an alternative technique to epidural analgesia for labour, but its benefits are not clearly identified. METHODS: A prospective, blinded, randomized study was undertaken involving 113 women attending a university hospital obstetric department. Analgesia was initiated with intrathecal bupivacaine 0.25% 1 mL + sufentanil 5 microg in the combined spinal-epidural group (n = 54), and with bupivacaine 0.125% + epinephrine 2.5 microg mL(-1) + sufentanil 7.5 microg in the epidural group (n = 59). In both cases this was followed by patient-controlled epidural analgesia with bupivacaine 0.125% (+ sufentanil 0.25 microg mL(-1)). Duration of labour, quality of analgesia and side-effects were compared between groups. RESULTS: In the combined spinal-epidural group, the onset of analgesia was faster (5 vs. 15 min, P < 0.001), the consumption of bupivacaine was lower (7.5 vs. 11.3 mg h(-1), P = 0.003) and there was less unilateral analgesia (14.8% vs. 40.7%, P = 0.002) than in the epidural group. The characteristics of labour were similar in both groups. However, in the combined spinal-epidural group, there was a higher incidence of posterior presentation (25.9% vs. 10%, P = 0.03), pruritus (P < 0.001), hypotension (P = 0.002), somnolence (P = 0.01), nausea (P = 0.02) and one case of meningitis. CONCLUSIONS: The combined spinal-epidural technique provided more effective analgesia during labour than epidural analgesia alone but offered no other advantage. It induced more adverse effects and this should be considered before routinely using the combined spinal-epidural technique.

Adult↗
PubMed2004

Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries.

The formation of misaligned scar tissue by a variety of cell types expressing multiple axon growth inhibitory proteoglycans presents a physical and molecular barrier to axon regeneration after adult spinal cord injuries. Decorin is a small, leucine-rich proteoglycan that has previously been shown to reduce astrogliosis and basal lamina formation in acute cerebral cortex stab injuries. We have therefore tested whether mini pump infusion of hr-decorin into acute stab injuries of the adult rat spinal cord can not only inhibit formation of an astroglial limitans but also deposition of the axon growth inhibitory proteoglycans neurocan, NG2, phosphacan and brevican. Combined immunohistochemical and quantitative Western blot analysis revealed major reductions in levels of core protein expression (>80% for 130-kDa neurocan, 145/80-kDa brevican, 300-kDa phosphacan) and immunoreactivity for all four chondroitin sulfate proteoglycans (CSPGs) within decorin-treated injuries compared with untreated controls. Astrogliosis within lesion margins and the accumulation of OX42+ macrophages/microglia within lesion centres were also significantly reduced. These decorin-induced changes in scar formation combined to promote the striking ability of axons from microtransplanted adult sensory neurons to enter, grow within and exit decorin-infused spinal cord injuries, in sharp contrast to the complete failure of axons to cross untreated, CSPG-rich lesions. Decorin pretreatment of meningial fibroblasts in vitro also resulted in a three-fold increase in neurite outgrowth from co-cultured adult sensory neurons and suppression of NG2 immunoreactivity. The ability of decorin to promote axon growth across acute spinal cord injuries via a coordinated suppression of inflammation, CSPG expression and astroglial scar formation make decorin treatment a promising component of future spinal cord regeneration strategies.

Animals↗
PubMed1995

[Radiotherapy and concomitant cisplatin in stage III non-small cell bronchial cancer: results of a pilot study].

From July 1989 to July 1991, 73 previously untreated patients with histologically proven stage III inoperable non-small cell lung cancer have been treated with standard fractionation radiation therapy and concomitant cisplatin by continuous infusion. Thoracic irradiation was delivered at a dose of 40 grays in 20 fractions over 4 weeks to the entire mediastinum, ans was followed after a two-week rest by a boost of 30 grays in 15 fractions over 3 weeks with oblique fields sparing the spinal cord. Continuous infusion cisplatin was given during the second week or each radiation therapy sequence at a dose of 20 mg/sqm/24 hours during five days (120 hours) with usual hyperhydratation and antiemetic measures. Toxicity was essentially hematologic and gastro-intestinal but there was only 4.1% grade 3 or grade 4 complications. Radical surgery became feasible after the first cycle of treatment in 10 patients (13.7%). Complete response rate as determined by CT-scan and fiberoptic bronchoscopy was 61.6%. At a median follow-up of 26 months, actuarial overall survival at 1, 2 and 3 years was 46.6%, 27.7% and 24.5%, respectively. There were no local recurrence or distant relapses after 3 years, which will hopefully result in long-term survival in one quarter of these patients. These results compare favorably with other studies combining radiation therapy and concomitant cisplatin with different dosage and schedule. Local control appears substantially improved by this combined modality treatment over radiation therapy alone. However, the incidence of distant metastasis remains significant, especially during the first year of follow-up. Further improvement of early and long-term survival could possibly result from the incorporation in this protocol of a second drug active against subclinical dissemination.

Actuarial Analysis↗
PubMed1996

Pre-eclampsia: the effect of intravenous fluid preload on atrial natriuretic peptide secretion during caesarean section under spinal anaesthesia.

BACKGROUND: The haemodynamic effect of volume load at elective Caesarean delivery may be modulated by atrial natriuretic peptide (ANP) especially in pre-eclamptic women in whom basal ANP levels are increased. METHODS: We followed the haemodynamic parameters and determined the peripheral venous levels of ANP before and after an intravenous volume preload of 1000 ml of Ringer's acetate solution, followed by a further load of the same volume under spinal anaesthesia in 7 healthy and in 6 pre-eclamptic women. RESULTS: During the preload period the median ANP level increased more (from 14.8 to 22.1 pmol/l, P = 0.03) in pre-eclamptic than in healthy women (from 8.0 to 8.5 pmol/l, NS); while an increment in central venous pressure (CVP) was also greater in pre-eclamptic than in healthy women. The increase in the concentrations of ANP correlated significantly (P < 0.05) with the increase in CVP in the total study group. A significant increase in ANP levels in healthy pregnant women was not seen until during the second infusion period under spinal anaesthesia; in pre-eclamptic women the levels increased further during that period. CONCLUSION: These findings concur with the theory that atrial stretch is a stimulus for ANP release. An exaggerated release of ANP in response to volume loading may aid in the adaptation of maternal circulation to volume load at elective Caesarean delivery in pre-eclamptic women.

Adult↗
PubMed1962

An investigation of the action of tyramine and its interrelationship with the effects of other sympathomimetic amines.

Choline 2,6-xylyl ether potentiated the sympathomimetic effects of tyramine and adrenaline in anaesthetized and spinal cats; the effects of noradrenaline were not significantly affected. The pressor activity of tyramine was also potentiated by the drug in reserpine-treated spinal cats and in pithed rats. The acute intravenous injection of reserpine in pithed rats potentiated pressor responses to tyramine, but depressed those to adrenaline and noradrenaline. During the intravenous infusion of noradrenaline in spinal cats and pithed rats the pressor responses to tyramine were increased, whilst those to adrenaline and noradrenaline were decreased. Infusion of isoprenaline in a spinal cat depressed responses to tyramine and noradrenaline, but potentiated those to adrenaline. A lower rate of infusion of isoprenaline in the same animal subsequently potentiated adrenaline and noradrenaline, but continued to depress tyramine. These results are held to be inconsistent with the view that the sympathomimetic effects of tyramine are produced entirely by the release of catechol amines.

Amines↗
PubMed1991

Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats.

Systemic administration of the phosphodiesterase inhibitor rolipram (0.05-10.0 mg/kg, IP) produced a rapid and dose-related increase in the amplitude of the acoustic startle response in rats. The (-) isomer was more potent than the (+) isomer in enhancing startle amplitude. Rolipram increased startle responses that were elicited by brief electrical stimulation of the ventral cochlear nucleus or nucleus reticularis pontis caudalis, two brainstem relay nuclei of the startle neural circuit. A low (5 micrograms) dose of rolipram produced an excitatory effect on startle following spinal (lumbar intrathecal) infusion but not following supraspinal (lateral ventricle) infusion. Rolipram (0.5 mg/kg, IP) excitation of startle was not blocked by drugs which differentially disrupt the release of monoamines (DSP4, reserpine + alpha-methyl-para-tyrosine, reserpine + para-chloro-phenylalanine) or by drugs which differentially block monoamine receptors (haloperidol, prazosin, idazoxan, cinanserin, or cyproheptadine). The marked increase in startle seen following systemic rolipram injection is attributable, at least in part, to an action in the lumbar spinal cord that directly or indirectly facilitates neural transmission along the reticulospinal component of the startle reflex neural pathway. The startle reflex should be a useful behavioral test system for studying the mechanism of action of rolipram and related compounds purported to selectively inhibit calmodulin-independent forms of phosphodiesterase.

Acoustic Stimulation↗
PubMed1983

GnRH in the spinal subarachnoid space potentiates lordosis behavior in the female rat.

Gonadotropin releasing hormone (GnRH) (100 ng) infused directly into the spinal subarachnoid space via a chronically implanted catheter, induced a prompt facilitation of lordosis behavior in estrogen-primed ovariectomized female rats. Facilitation occurred within 5 min and lasted for 3 1/2 hr. This effect of GnRH could be blocked by a GnRH antagonist analog, [D-Phe2, Pro3, D-Phe6] GnRH (250 ng) which also completely abolished lordosis within 2 1/2 hr. The antagonist analog (250 ng) but not a high titre specific anti-GnRH antiserum (enough to neutralize 24 micrograms of GnRH) abolished lordosis when infused alone in the subarachnoid space in estrogen-primed rats. The antagonist but not the anti-GnRH antiserum also significantly suppressed lordosis in estrogen-progesterone primed female rats. Supporting experiments showed that the effects of GnRH and its antagonist may not be due to their effects on supraspinal structures by diffusion from the spinal subarachnoid space. These results may indicate a direct effect of GnRH and its antagonist at the level of the spinal cord and may suggest a possible role for GnRH in the processing of somatosensory information necessary for the trigger of lordosis.

Animals↗
PubMed2000

Epidural versus subdural spinal cord cooling: cerebrospinal fluid temperature and pressure changes.

BACKGROUND: Regional spinal cord cooling can increase the tolerable duration for spinal cord ischemia resulting from aortic clamping. We compared the efficacy of epidural and subdural cooling and the effect of the resulting cerebrospinal fluid-pressure (CSF) increases on spinal cord motor neuron function. METHODS: In 8 pigs, CSF temperature and pressure were assessed in the subdural space at L4, T15, and T7. Saline was infused at 333, 666, and 999 ml/h at four consecutive locations: L4 subdural, L4 epidural, T15 subdural, and T15 epidural. First, the influence of CSF-pressure increases during normothermic infusion on transcranial motor evoked potentials (tc-MEPs) was assessed. Then, hypothermic infusion (4 degrees C) was performed to assess CSF-temperature changes. RESULTS: During normothermic infusion, baseline CSF pressures increased uniformly from 6 +/- 4 mm Hg to 34 +/- 18, 42 +/- 17, and 50 +/- 18 mm Hg with increasing infusion rates (p < 0.001), and did not differ between epidural or subdural infusion. Tc-MEPs indicated spinal cord ischemia in 6 animals when CSF pressures reached 65 +/- 11 mm Hg. During hypothermic infusion, CSF temperatures decreased from 37 degrees to 35 +/- 1.2 degrees, 31 +/- 2.2 degrees, and 28 +/- 2.8 degrees C, but increasing CSF-temperature gradients were observed between the infusion location and distant segments. Subdural cooling resulted in lower CSF temperatures (p < 0.001), but caused larger CSF-pressure increases (p < 0.001). CONCLUSIONS: Subdural and epidural infusion cooling produce localized spinal cord hypothermia in pigs. The concurrent pressure increases, however, are uniformly distributed and can result in tc-MEP evidence of ischemia.

Animals↗
PubMed2002

Retrograde repression of growth-associated protein-43 mRNA expression in rat cortical neurons.

Corticospinal neurons support rapid growth of axons toward spinal cord targets in the perinatal period. Initial axon growth is accompanied by elevated expression of growth-associated protein-43 (GAP-43), which then declines in postnatal development. To investigate whether expression of GAP-43 mRNA is regulated by retrograde signals, we injected colchicine into the corticospinal tract to block retrograde axonal transport during a time when GAP-43 is normally declining in corticospinal neurons. Colchicine caused a prolongation of high GAP-43 mRNA expression in neurons located in layer V (but not other layers) of sensorimotor cortex. We next used osmotic minipumps to infuse soluble adult spinal cord extract into the sensorimotor cortex. This resulted in a premature downregulation of GAP-43 mRNA in identified corticospinal neurons. GAP-43 repressive activity was found in extracts of the spinal cord tissue as young as postnatal day 8. The effect of spinal cord extract in vivo was not mimicked by adult cerebellar or muscle extracts. Cultures of postnatal cortical neurons also underwent downregulation of GAP-43 mRNA when treated with spinal cord extract. Activation of cAMP signaling also repressed GAP-43 mRNA in cortical cultures, and the repressive effect of spinal cord extract was diminished by an adenyl cyclase inhibitor. Thus, GAP-43 mRNA may be downregulated late in development by a target-derived retrograde repressive factor, and this effect may be mediated by cAMP second messenger signaling.

Animals↗
PubMed1991

Characteristics of precipitated withdrawal from spinal morphine: changes in [Met5]enkephalin levels.

This investigation was carried out to study the development of physical dependence on spinally administered morphine, and it was determined if this phenomenon is associated with altered levels of [Met5]enkephalin. Morphine was infused continuously into the intrathecal space of rats for three or six days. In morphine-dependent animals, an intrathecal naloxone challenge produced increased reaction to nociceptive stimuli, hypertension, hyperthermia, decreased urinary output, and loss of body weight. Chronic spinal infusion of morphine alone failed to alter levels of [Met5]enkephalin in sacral and lumbar spinal cord. However, 24 h after the naloxone challenge, there was a significant increase in spinal enkephalin levels in morphine-dependent animals. It is concluded that spinal morphine treatment leads to the development of physical dependence. Certain characteristics of this phenomenon, as reflected in the naloxone-precipitated withdrawal signs, differ from those associated with dependence on systemic morphine.

Analgesics↗
PubMed2004

Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for Caesarean section.

BACKGROUND: During spinal anaesthesia for Caesarean section, the optimal phenylephrine regimen and the optimal blood pressure (BP) to which it should be titrated are undetermined. The ideal regimen would balance efficacy for maintaining uteroplacental perfusion pressure against potential for uteroplacental vasoconstriction, both of which may affect fetal acid-base status. We compared phenylephrine infusion regimens based on three different BP thresholds. METHODS: After intrathecal injection, we infused phenylephrine 100 microg min(-1) for 2 min. Then, until delivery, we infused phenylephrine whenever systolic BP (SBP), measured every 1 min, was below a randomly assigned percentage of baseline: 100% (Group 100, n=25), 90% (Group 90, n=25) or 80% (Group 80, n=24). We compared umbilical blood gases, Apgar scores and maternal haemodynamics and symptoms. RESULTS: Patients in Group 100 had fewer episodes [median 0 (range 0-8)] of hypotension (SBP <80% baseline) compared with Group 80 [5 (0-18)] and Group 90 [2 (0-7)] (P<0.001 in each instance). Total dose of phenylephrine was greater in Group 100 [median 1520 microg (interquartile range 1250-2130 microg)] compared with Group 90 [1070 (890-1360) microg] and Group 80 [790 (590-950) microg]. Umbilical arterial pH was greater in Group 100 [mean 7.32 (95% confidence interval 7.31-7.34)] than in Group 80 [7.30 (7.28-7.31)] (P=0.034). No patient had umbilical arterial pH <7.2. In Group 100, 1/24 (4%) patients had nausea or vomiting compared with 4/25 (16%) in Group 90 and 10/25 (40%) in Group 80 (P=0.006). CONCLUSIONS: For optimal management, phenylephrine should be titrated to maintain maternal BP at near-baseline values.

Adult↗