Xenon administration immediately after but not before or during cardiopulmonary bypass with cerebral air embolism impairs cerebral outcome in rats.

CONTEXT: The neuroprotective properties of xenon might improve cerebral outcome after cardiac surgery using cardiopulmonary bypass. However, in the presence of cerebral air emboli, xenon impaired cognitive and histological outcome in a rat cardiopulmonary bypass model, a result which is due to the property of xenon to expand air bubbles. OBJECTIVE: The current study was designed to assess whether cerebral outcome in the setting of cardiopulmonary bypass with cerebral air embolism could be altered by administration of xenon restricted to periods when the occurrence of cerebral air embolism is unlikely. DESIGN: With institutional review board approval, 40 rats were allocated randomly to one of four groups (n = 10) which determined the period of xenon inhalation: 'before', 'during' or 'after' cardiopulmonary bypass or 'none'. SETTING: Rats were subjected to 90  min of normothermic cardiopulmonary bypass combined with 10 small cerebral air emboli. Xenon was administered according to group assignment: the 'none' group received no xenon; in the other groups, the lungs were ventilated with 56% xenon before, during or after cardiopulmonary bypass and cerebral air embolism. MAIN OUTCOME MEASURES: Motor and cognitive outcomes were tested using the modified hole-board test. Cerebral infarction volumes were determined on postoperative day 21. RESULTS: Animals that received xenon after cardiopulmonary bypass and cerebral air embolism had impaired motor function scores [after: median 6.6 (range 0.25-8), before: 0.5 (0-3), during: 1.5 (0.25-2.75), none: 1 (0-1.75)] and cognitive performance [after: 9 (6.5-9), before: 0 (0-5.5), during: 1 (0-5.5), none: 1 (0-4)] compared with all other groups (P < 0.05). Administration of xenon after cardiopulmonary bypass and cerebral air embolism also led to larger cerebral infarction volumes [after: 74 µl (54-157), before: 45 µl (20-82), during: 33 µl (23-54), none: 22 µl (17-78)] compared with the groups that received xenon during cardiopulmonary bypass and cerebral air embolism or no xenon at all (P < 0.05). CONCLUSION: Xenon administered immediately after cardiopulmonary bypass and cerebral air embolism impaired motor, cognitive and histological outcome in rats. At no time did inhalation of xenon lead to any beneficial effects on cerebral outcome when compared with inhalation of nitrogen.

Chronic Escherichia coli infection induces muscle wasting without changing acetylcholine receptor numbers.

OBJECTIVE: Muscle weakness in septic patients is a serious problem as it complicates and lengthens hospital stays, prolongs rehabilitation and increases costs. We examined the effects of a chronic infection with Escherichia coli on muscle function, muscle mass, and the expression of nicotinic acetylcholine receptors (AChRs). DESIGN AND SETTING: Prospective, randomized animal study in an animal laboratory, university hospital. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: A catheter was implanted into the external jugular vein of anesthetized rats, and a dose of 3.2x10(8) CFU of E. coli bacteria was injected; the catheter was then sealed and tunneled subcutaneously. MEASUREMENTS AND RESULTS: Animals injected with E. coli bacteria showed a significant decrease in body and muscle mass over the 14-day experimental period. Neuromuscular function was tested by mechanomyography on days 3, 7, and 14 following injection. Tetanic tension decreased over the time course of sepsis, without effecting tetanic fade. Serum levels of acute-phase protein, alpha1-acid glycoprotein, were increased by day 3, and remained significantly higher until day 14. AChRs were quantitated using 125I-labeled bungarotoxin and revealed no differences between groups. CONCLUSIONS: Central venous injection of E. coli bacteria induces systemic inflammation evidenced as loss of body weight, muscle mass and increased alpha1-acid glycoprotein levels. The inflammation-induced muscle weakness is due to muscle atrophy and not to upregulated AChRs. This model may prove useful for studying maneuvers to prevent muscle wasting with inflammation.