Perkins, William J.

The present study was designed to determine if the noncompetitive excitatory amino acid antagonist, dizocilpine maleate, when administered after a 17 min period of complete cerebral ischemia in primates, would improve postischemic neurologic function and hippocampal histopathologic outcome when compared to placebo-treated animals. Ten pigtail monkeys were anesthetized and subjected to complete cerebral ischemia using an established neck tourniquet model. Five minutes postischemia, five monkeys received dizocilpine 300 μg/kg i.v. over 5 min, followed by an infusion of 150 μg/kg/h for 10 h. This produced plasma levels of the drug in excess of 30 ng/ml for the duration of the infusion. An additional five monkeys were treated with an identical volume of saline placebo. All monkeys received intensive care for the initial 24 to 48 h postischemia. At 96 h postischemia, there was no significant difference in neurologic function between the two groups ( p = 0.53, with the placebo group having the numerically better outcome). There also was no significant difference between hippocampal histopathology scores between dizocilpine and placebo-treated monkeys. The authors conclude that dizocilpine is not an efficacious therapy in the treatment of neurologic injury that occurs following complete cerebral ischemia in this primate model.

ABSTRACT OBJECTIVE Remote cerebellar hemorrhage (RCH) is an infrequent and poorly understood complication of supratentorial neurosurgical procedures. We retrospectively compared 42 patients who experienced RCH with a case-matched control cohort, to delineate risk factors associated with the occurrence of this complication. METHODS Between 1988 and 2000, 42 patients experienced RCH after supratentorial neurosurgical procedures at our institution. Diagnoses were made on the basis of postoperative computed tomographic or magnetic resonance imaging findings in all cases. The medical records for these patients were reviewed and compared with those for a control cohort of 43 patients, matched for age, sex, surgical lesion, and type of craniotomy, who were treated during the same period. RESULTS RCH most commonly occurred after frontotemporal craniotomies for unruptured aneurysm repair or temporal lobectomy and was frequently an incidental finding on postoperative computed tomographic scans. However, some cases of RCH were associated with significant morbidity, and two patients died. Preoperative aspirin use and elevated intraoperative systolic blood pressure were significantly associated with RCH (P = 0.026 and P = 0.036, respectively). Pathological findings for two cases demonstrated hemorrhagic infarctions in both. CONCLUSION RCH most commonly follows supratentorial neurosurgical procedures, performed with the patient in the supine position, that involve opening of cerebrospinal fluid cisterns or the ventricular system (such as unruptured aneurysm repair or temporal lobectomy). Preoperative aspirin use and moderately elevated intraoperative systolic blood pressure are potentially modifiable risk factors associated with the development of RCH. Although RCH can cause death or major morbidity, most cases are asymptomatic or exhibit a benign course. Cerebellar “sag” as a result of cerebrospinal fluid hypovolemia, causing transient occlusion of superior bridging veins within the posterior fossa and consequent hemorrhagic venous infarction, is the most likely pathophysiological cause of RCH.

Background The investigation examined whether primary alcohols could be used as tools to explore the mechanism of anesthetic actions in airway smooth muscle (ASM). The hypothesis was that, like volatile anesthetics, the primary alcohols relax intact ASM by decreasing intracellular Ca2+ concentration ([Ca2+]i) and by inhibiting agonist-induced increases in the force developed for a given [Ca2+]i (Ca2+ sensitivity). Method The effects of butanol, hexanol, and octanol on isometric force in canine tracheal smooth muscle were examined. The effects of hexanol on [Ca2+]i (measured with fura-2) and the relationship between force and [Ca2+]i were studied during membrane depolarization provided by KCl and during muscarinic stimulation provided by acetylcholine. Results The primary alcohols relaxed ASM contracted by KCl or acetylcholine in a concentration-dependent manner, with potency increasing as chain length increased. The alcohols could completely relax the strips, even during maximal stimulation with 10 microM acetylcholine (median effective concentrations of 28 +/- 12, 1.3 +/- 0.4, and 0.14 +/- 0.05 mM [mean +/- SD] for butanol, hexanol, and octanol, respectively). Hexanol decreased both [Ca2+]i and force in a concentration-dependent manner. Hexanol decreased Ca2+ sensitivity during muscarinic stimulation but had no effect on the force-[Ca2+]i relationship in its absence. Conclusions Primary alcohols produce reversible, complete relaxation of ASM, with potency increasing as chain length increases, by decreasing [Ca2+]i and inhibiting increases in Ca2+ sensitivity produced by muscarinic receptor stimulation. These actions mimic those of volatile anesthetics on ASM, a circumstance suggesting that the primary alcohols may be useful tools for further exploring mechanisms of anesthetic effects on ASM.