Neuroprotective effects and suppression of ischemia-induced glutamate elevation by ß1-adrenoreceptor antagonists administered before transient focal ischemia in rats.

BACKGROUND: ß-Adrenoreceptor antagonists provide neuroprotective effects after focal cerebral ischemia in experimental settings. This study was conducted to compare the neuroprotective effects of low-dose and high-dose of selective ß1-adrenoreceptor antagonists in rats after focal cerebral ischemia. We also investigated whether glutamate and norepinephrine contribute to neuroprotection of the ß-adrenoreceptor antagonists. METHODS: Sprague-Dawley rats were subjected to 120 minutes middle cerebral artery occlusion. The rats received intravenous infusion of saline 0.5 mL/h, esmolol 200, esmolol 2000, landiolol 50, or landiolol 500 µg/kg/min. Infusion of all the drugs were started 30 minutes before ischemia and continued for 24 hours. Neurological deficit scores were evaluated at 1, 4, and 7 days, whereas the brains were removed and stained at 7 days after ischemia. In the esmolol 200, and landiolol 50 µg/kg/min groups of additional rats, glutamate and norepinephrine concentrations in the striatum were measured separately by microdialysis during ischemia (glutamate, 120 min; norepinephrine, 110 min) and reperfusion (40 min). RESULTS: Neurological deficit scores were smaller in rats treated with esmolol or landiolol than in saline-treated rats at 1, 4, and 7 days. The cortical and striatal infarct volumes were smaller in rats receiving ß-adrenoreceptor antagonists than in the saline-treated rats. There were no significant differences in neurological score or infarct volume between the groups receiving the different doses of ß1-adrenoreceptor antagonists. The area under the curve of glutamate in the esmolol-treated or landiolol-treated rats was significantly smaller than that in the saline-treated rats, whereas no significant differences were noted in the norepinephrine concentration among the groups. CONCLUSIONS: This study indicates that the improvement in neurological and histologic outcomes by selective ß1-adrenoreceptor antagonists after transient focal cerebral ischemia is partly attributed to attenuation of glutamate release.

[Preface and comments: Protection of the brain and the spinal cord].

Basic and clinical investigations have been performed, focusing on the mechanism of ischemic brain and spinal cord injuries, and preventive measures against ischemic insults such as drug therapy, hypothermia, maintenace of blood flow to brain and spinal cord, preconditioning, and no use of high dose fentanyl. In this special issue, five experts have provided new relevant information concerning brain and spinal cord protection. Further research in brain and spinal cord protection will contribute to better understanding of ischemic central nervous system injuries and to the establishment of novel therapies for protection of central nervous system.

Physicochemical compatibility of propofol-lidocaine mixture.

UNLABELLED: To examine the physicochemical stability of combinations of propofol-lidocaine mixtures frequently used in clinical practice, we added lidocaine 5, 10, 20, or 40 mg to commercially available 1% propofol 20 mL. To assess chemical stability, propofol concentrations were determined by gas chromatography assay for 24 h after preparation of the mixture. In addition, scanning electron microscopy was used to determine the maximum detectable droplet size in randomly selected fields. Macroscopically, separate, colorless layers were first seen at 3 and 24 h after the addition of 40 and 20 mg of lidocaine to propofol, respectively, whereas the mixture with 5 or 10 mg of lidocaine was macroscopically stable. Propofol concentrations in the mixture with 40 mg of lidocaine decreased linearly and significantly from 4 to 24 h after preparation, whereas those combined with other lidocaine doses were unchanged compared with baseline concentrations. Scanning electron microscopy showed that droplets with diameters >or=5 microm first appeared 30 min after the addition of 40 mg of lidocaine to propofol, and the emulsion droplets were enlarged in a time- and dose-dependent fashion. Our results indicate that the addition of lidocaine to propofol results in a coalescence of oil droplets, which finally proceeds to a visible separate layer. Depending on the dose of lidocaine and the duration between its preparation and administration, this combination may pose the risk of pulmonary embolism. IMPLICATIONS: The addition of lidocaine to propofol results in time- and dose-dependent increases in oil droplet diameters in emulsion. This mixture is physicochemically unstable over time and may cause pulmonary embolism, depending on the dose of lidocaine.

[Postoperative analgesia with morphine with or without diclofenac after shoulder surgery].

Balanced analgesia using a narcotic and a nonsteroidal anti-inflammatory drug has been successfully tested for postoperative analgesia. This study was designed to examine the efficacy of such combination therapy after shoulder surgeries. Twenty ASA physical status I or II patients, scheduled for shoulder surgeries under general anesthesia, were randomly assigned to either morphine (M) group (n = 10), who received IV morphine patient-controlled analgesia (PCA) alone (2 mg as a bolus, lock-out interval of 10-minutes, and 10 mg as 1-hour limit for 48 hours), or morphine + diclofenac (M + D) group (n = 10), who received, in addition to morphine PCA, diclofenac suppositories 50 mg.8 h-1 starting immediately before surgical incision for 48 hours. Postoperative analgesic profiles, such as visual analog scale (VAS) at rest and on movement, and cumulative morphine consumption, the incidence and extent of side effects (nausea, vomiting, and time till the first bowel movement), and other complications were recorded. The two groups were similar demographically. Patients in the M + D group required 15.1 +/- 9.0 mg of morphine within 48 hours after surgery, while those in the M group required 30.5 +/- 21.0 mg of morphine (P < 0.05). No significant differences in VAS at rest and on movement were observed between the two groups. The time till the first bowel movement was significantly shorter in the M + D group. Our data suggest that diclofenac suppositories 50 mg.8 h-1 starting immediately before surgery for 48 h are effective adjuvant in reducing post-shoulder surgery morphine requirement and retardation of bowel movement.