Biomedical subjects

Ansgar M Brambrink

Publications and source records attributed to Ansgar M Brambrink.

11 recordsLinked to original sources

PubMed2006

The antibiotic erythromycin induces tolerance against transient global cerebral ischemia in rats (pharmacologic preconditioning).

BACKGROUND: Cerebral ischemic tolerance can be induced by a variety of noxious stimuli, but no clinically applicable regimen for preconditioning has been described. Therefore, the authors tested the ability of a pharmacologic preconditioning strategy using the well-known macrolide antibiotic erythromycin to induce tolerance against transient global cerebral ischemia in vivo. They also investigated whether tolerance induction by erythromycin involves transcriptional and translational changes of cerebral B-cell leukemia/lymphoma-2 (bcl-2) expression. METHODS: Male Wistar rats were treated with erythromycin (25 mg/kg intramuscularly) or vehicle and subjected to 15 min of transient global cerebral ischemia 6, 12, or 24 h after pretreatment. Neurologic deficit was evaluated once daily, and neuronal cell survival was assessed after 7 days of reperfusion. Additional animals were similarly pretreated, and cerebral bcl-2 messenger RNA (mRNA) and protein expression was analyzed 6 and 24 h later. RESULTS: Erythromycin improved postischemic neuronal survival in hippocampal CA1 and CA3 sectors and reduced functional deficit, with 12 h being the most efficient pretreatment interval. Bcl-2 mRNA in hippocampus was transiently up-regulated 6 h after erythromycin, but neuronal Bcl-2 protein remained unchanged. CONCLUSIONS: Erythromycin can induce cerebral ischemic tolerance in vivo (pharmacologic preconditioning), suggesting a potential clinical strategy of preemptive neuroprotection. Changes in bcl-2 expression after erythromycin were small and transient. The induction of bcl-2-related pathways, although important for other preconditioning regimens, may therefore be less relevant for the neuroprotective effects of pharmacologic preconditioning using erythromycin.

Animals↗

PubMed2006

Brain protection by anesthetic agents.

PURPOSE OF REVIEW: Patients at risk for perioperative stroke, or those who have suffered recent cerebral injury, may benefit from neuroprotective properties of anesthetic agents during surgery. This manuscript reviews recent clinical and experimental evidence for neuroprotective effects of common anesthetic agents, and presents potential mechanisms involved in anesthetic neuroprotection. RECENT FINDINGS: Although strong experimental data support a neuroprotective potential of several anesthetic agents, specifically isoflurane and xenon, consistent long-term protection by either agent has not been demonstrated. Unfortunately, there is a lack of clinical studies that would support the use of any one anesthetic agent over the others. Mechanisms of neuroprotection by anesthetic agents appear to involve suppression of excitatory neurotransmission, and potentiation of inhibitory activity, which may contribute to the reduction of excitotoxic injury. Activation of intracellular signaling cascades that lead to altered expression of protective genes may also be involved. SUMMARY: Solid experimental evidence supports neuroprotection by anesthetic agents. It is too early to recommend any specific agent for clinical use as a neuroprotectant, however. Further study is warranted to unravel relevant mechanisms and to appreciate the potential clinical relevance of experimental findings.

Anesthetics↗

PubMed2006

An early bolus of hypertonic saline hydroxyethyl starch improves long-term outcome after global cerebral ischemia.

OBJECTIVE: The beneficial effect of hypertonic saline solutions in the emergency treatment of shock and traumatic brain injury is well described. The present study determines effects of a single bolus of hypertonic saline on long-term survival, neurologic function, and neuronal survival 10 days after global cerebral ischemia. In addition, we evaluated the therapeutic window for hypertonic saline treatment (early vs. delayed application). DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Male Wistar rats weighing 240-330 g. INTERVENTIONS: Rats were submitted to temporal global cerebral ischemia using temporary bilateral carotid occlusion combined with hypobaric hypotension. Animals received 7.5% saline/6% hydroxyethyl starch (HHS) or vehicle (NaCl 0.9%) at either 1.5 mins (early treatment) or 31.5 mins (delayed treatment) of reperfusion. Regional cerebral blood flow (rCBF) and physiologic variables were measured during insult and early reperfusion. Animal survival and neurologic function were evaluated throughout the 10-day observation period. Quantification of brain injury was performed on day 10. MEASUREMENTS AND MAIN RESULTS: Early treatment with HHS resulted in a robust restoration of rCBF after ischemia, reduced postischemic mortality by 77% (9% vs. 39% in vehicle-treated controls), ameliorated neurologic performance (Neuro-Deficit-Score 10 days after insult, 96 +/- 0.7 vs. 85 +/- 1.4, mean +/- se), and almost blunted neuronal cell death (hippocampal CA1, 2150 +/- 191 vs. 884 +/- 141 neurons/mm; cortex, 1746 +/- 91 vs. 1060 +/- 112). In contrast, delayed treatment resulted in no sustained effects. CONCLUSIONS: Timing of HHS treatment is critical after experimental global cerebral ischemia to reduce mortality, improve neurologic function, and neuronal survival. Our results suggest that early application of HHS may be a potential neuroprotective strategy after global cerebral ischemia.

Animals↗

PubMed2005

Airway management in infants and children.

Anaesthesiologists, paediatricians, paediatric intensivists and emergency physicians are routinely challenged with airway management in children and infants. There are important differences from adult airway management as a result of specific features of paediatric anatomy and physiology, which are more relevant the younger the child. In addition, a number of inherited and acquired pathological syndromes have significant impact on airway management in this age group. Several new devices--e.g. different types of laryngeal mask airways in various sizes, small fibre-endoscopes--have been introduced into clinical practice with the intention of improving airway management in this age group. Important new studies have gathered evidence about risks and benefits of certain confounding variables for airway problems and specific techniques for solving them. Airway-related morbidity and mortality in children and infants during the perioperative period are still high, and only a thorough risk determination prior to and continuous attention during the procedure can reduce these risks. Appropriate preparation of the available equipment and frequent training in management algorithms for all personnel involved appear to be very important.

Child↗

PubMed2005

Fiberoptic techniques.

Fiberoptic intubation of the spontaneously breathing patient is the gold standard and technique of choice for the elective management of a difficult airway. In the hands of the properly trained and experienced user, it is also an excellent 'plan B' alternative when direct laryngoscopy unexpectedly fails. Fiberscope-assisted intubation through an endoscopy face mask, laryngeal mask airway or intubating laryngeal mask airway secures ventilation and oxygenation, and permits endotracheal intubation in airway emergency situations. Portable fiberscopes can be used in remote settings, increasing patient safety. This review discusses current fiberoptic intubation techniques and their applications in the management of both the anticipated and unanticipated difficult airway.

Administration, Topical↗

PubMed2004

Traumatic brain injury in children--clinical implications.

Traumatic brain injury (TBI) is the leading cause of death in childhood; however only very few studies focusing on the specific pathophysiology and treatment have been published to date. Head trauma is more likely in young children than in adults given the same deceleration of the body due to their large and heavy heads and weak cervical ligaments and muscles. Resulting brain injury is more severe due to their thin, pliable skulls and the yet unfused sutures. Accordingly, children below the age of 4 years have lower chances of a full recovery after severe TBI, although in general, neurologic recovery after severe brain injury in children is better than in adults. The time course of brain injury can be divided into two steps: primary and secondary injury. Primary brain injury exclusively results from the initial impact. In contrast, adverse physiologic conditions during recovery after head trauma may account for additional brain damage, which is then referred to as secondary brain injury. As primary brain injury can only be influenced by preventive measures, all therapeutic efforts during the post-injury period focus on the reduction of secondary injury to the traumatized brain. Several mechanisms have been identified to be involved in the development of post-traumatic secondary brain injury, which render the rationale for the key treatment strategies. Three evidence based measures are of critical importance to prevent or minimize secondary brain injury: (1) avoid hypoxemia, (2) avoid post-traumatic arterial hypotension, and (3) refer the traumatized child to an experienced trauma team at a center that provides the availability of special equipment, e.g. for surgical procedures and airway management, for this age group. For several other therapeutical means, e.g. hypothermia or specific surgical interventions, clinical evidence to date is insufficient to allow recommendation as rescue treatment for children at risk of severe neurological sequelae following TBI. This review discusses the clinical implication of pathophysiologic mechanisms of TBI in the developing brain according to the recent literature and current guidelines. It follows the clinical approach to a head injured child, that can be divided into three phases, i.e. initial assessment and stabilization, followed by first tier, and if necessary second tier therapeutic interventions to assure adequate oxygenation and perfusion of the brain.

Adolescent↗

PubMed2004

The effect of anti-L-selectin (aselizumab) in multiple traumatized patients--results of a phase II clinical trial.

OBJECTIVE: The objectives of this study were to evaluate safety (primary) and clinical efficacy (secondary) of the humanized monoclonal anti-L-selectin antibody aselizumab in severely injured patients. DESIGN: Prospective phase II, parallel group, double-blind, randomized, placebo-controlled clinical trial. SETTING: Fourteen medical intensive care units or trauma units in level I trauma centers in Belgium, Germany, and Poland. PATIENTS: Eighty-four patients with a sustained trauma due to a blunt or penetrating injury and a total Injury Severity Scale score of > or =25. INTERVENTIONS: Patients received either aselizumab at dosages of 0.5, 1, or 2 mg/kg or placebo within 6 hrs of the traumatic event and were followed for 6 wks. MEASUREMENTS AND MAIN RESULTS: The number of expeditable adverse events increased dose dependently over the aselizumab groups compared with placebo. There were no statistically significant differences between all groups regarding leukopenia and risk of infection. No immunologic response following infusion of aselizumab was noted. The number of patients with multiple organ failure, defined as a median value of the total Goris Multiple Organ Failure score of > or =5 on > or =2 consecutive days within 14 days, was not significantly different for the 0.5 mg/kg, 1 mg/kg, 2 mg/kg, and placebo groups. There were no statistically significant differences in time of mechanical ventilation, length of stay in an intensive care unit, and total duration of hospitalization between treatment groups. CONCLUSIONS: Aselizumab was associated with a higher rate of infections and leucopenia; however, this difference was not significantly different compared with placebo. For all efficacy variables, aselizumab presented no significant trends but only a few scattered statistically significant differences between groups.

Adolescent↗

PubMed2003

Prehospital advanced trauma life support: how should we manage the airway, and who should do it?

Adequate oxygenation at all times is of paramount importance to the critically injured patient to avoid secondary damage. The role of endotracheal intubation in out-of-hospital advanced trauma life support, however, remains controversial. Initiated by a recent observational study, this commentary discusses risks and benefits associated with prehospital intubation, the required personnel and training, and ethical implications. Recent evidence suggests that comprehensive ventilatory care already initiated in the field and maintained during transport may require the presence of a physician or another adequately skilled person at the scene. Benefits of such as service need to be balanced against increased costs.

Advanced Cardiac Life Support↗

PubMed2003

Nitration of the striatal Na,K-ATPase alpha3 isoform occurs in normal brain development but is not increased during hypoxia-ischemia in newborn piglets.

Neonatal hypoxia-ischemia (HI) can result in significant sensorimotor abnormalities, including movement and posture disorders. These neurological impairments are believed to result from basal ganglia (striatum) damage, but the exact cause of this injury is not known. One mechanism involved in brain injury after HI is the generation of reactive oxygen species, which damage cellular macromolecules. We tested the hypothesis that inactivation of plasma membrane enzyme Na,K-ATPase during striatal neurodegeneration after HI emerges with peroxynitrite attack on the enzyme. In vitro, reaction of peroxynitrite (100-500 microM) with purified Na,K-ATPase produced nitration of the alpha (catalytic) and beta (transport) subunits, as quantified by immunoblots of the reaction products for nitrotyrosine. To evaluate for peroxynitrite damage to Na,K-ATPase in vivo, striatal plasma membrane fractions from 1-week-old piglets subjected to asphyxic cardiac arrest and recovery were also studied by immunoprecipitation. During the progression of striatal neurodegeneration and loss of enzyme function 3-24 h after arrest, nitration of the alpha3 (neuronal) isoform of Na,K-ATPase was not increased relative to sham control. Suprisingly, however, nitration of this alpha isoform occurs during normal brain development and peaks at 2 weeks of age. We conclude that Na,K-ATPase is a target of peroxynitrite, but that this mechanism is not responsible for enzyme inactivation after HI. Protein nitration may serve as marker of other normal, noninjurious cell processes in the developing brain.

Animals↗

PubMed2002

Altered expression and phosphorylation of N-methyl-D-aspartate receptors in piglet striatum after hypoxia-ischemia.

The mechanisms for the profound degeneration of striatal neurons after hypoxia-ischemia in newborns are not understood. We hypothesized that this striatal neurodegeneration is related to N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. Using a 1-week-old piglet model of hypoxia-ischemia, we evaluated whether the expression and phosphorylation of NMDA receptor subunits in striatum are modified with severity of evolving neuronal injury after hypoxia-ischemia. Protein levels of NR1, phosphorylated NR1 897serine, NR2A and NR2B in striatum were measured by immunoblotting after piglets underwent hypoxic-asphyxic cardiac arrest, cardiopulmonary resuscitation, and recovery for 3, 6, 12 or 24 h. In membrane fractions isolated from total striatum, mean NR1 and NR2A levels did not change significantly with time after hypoxia-ischemia compared to control; however, the levels of both NR1 and phosphorylated NR1 897serine correlated with neuronal injury in putamen, with higher levels associated with greater neuronal injury in individual animals. NR2B levels were increased at 24 h after hypoxia-ischemia. Astrocyte expression of NR2B was prominent after hypoxia-ischemia. We conclude that NMDA receptors are changed in striatum after neonatal hypoxia-ischemia and that abnormal NMDA receptor potentiation through increased NR1 phosphorylation may participate in the mechanisms of striatal neuron degeneration after hypoxia-ischemia.

Aging↗

PubMed2002

Management of the paediatric airway: new developments.

During the last 2 years, some interesting new devices have been made available to improve airway management in children and infants, and several studies have advanced our understanding concerning risks and benefits of the current practice in the field. Certain risk factors for airway related problems during anaesthesia in children having a cold have been identified, and new aspects of the controversy concerning the use of cuffed endotracheal tubes in children presented. Novel video-assisted systems have been introduced for the management of the difficult airway in paediatric patients, and new applications for well known devices have been suggested, such as the laryngeal mask airway serving as guidance for fibreoptic intubation. Recent studies also demonstrated specific problems with the laryngeal mask airway in infants, as well as the advantages of a new prototypic laryngeal mask airway for children, similar to the ProSeal (LMA International S.A. Group, USA). Furthermore, the following review presents new data about the use of the cuffed oropharyngeal airway, the laryngeal tube, and the Arndt bronchus blocker in paediatric patients.

Journal Article↗