Takanobu Sano

EFFECTS OF PROPOFOL, ETOMIDATE, MIDAZOLAM AND FENTANYL ON MOTOR EVOKED RESPONSES TO TRANSCRANIAL ELECTRICAL OR MAGNETIC STIMULATION IN HUMANS

The effects of propofol, etomidate, midazolam, and fentanyl on motor evoked responses to transcranial stimulation (tc-MERs) were studied in five healthy human volunteers. Each subject, in four separate sessions, received intravenous bolus doses of propofol 2 mg.kg-1, etomidate 0.3 mg.kg-1, midazolam 0.05 mg.kg-1, and fentanyl 3 micrograms.kg-1. Electrical tc-MERs (tce-MERs) were elicited with anodal stimuli of 500-700 V. Magnetic tc-MERs (tcmag-MERs) were elicited using a Cadwell MES-10 magnetic stimulator at maximum output. Compound muscle action potentials were recorded from the tibialis anterior muscle. Duplicate tce-MERs and tcmag-MERs were recorded before and up to 30 min after drug injection. Reproducible baseline tce-MERs (amplitude 4.7 +/- 0.43 (SEM) mV, latency 29.4 +/- 0.35 ms) and tcmag-MERs (amplitude 3.7 +/- 0.43 mV, latency 31.1 +/- 0.39 ms) were obtained in all subjects. Pronounced depression of tce-MER amplitude to 2% of baseline values (P less than 0.01) was observed 2 min after injection of propofol. Thirty minutes after injection of propofol, amplitude depression to 44% of baseline (P less than 0.05) was still present, despite an apparent lack of sedation. Midazolam caused significant (P less than 0.01) amplitude depression, e.g., tcmag-MER to 16% of baseline values 5 min after injection. Significant depression persisted throughout the 30-min study period. Fentanyl did not cause any statistically significant amplitude changes in this small population. Etomidate caused significant but transient depression of tc-MER amplitude. However, there was considerable intersubject variability. Latency did not change significantly after any drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Mild and Moderate Hypothermia Provide Better Protection than a Burst-suppression Dose of Thiopental against Ischemic Spinal Cord Injury in Rabbits

Background: Controversy exists over the efficacy of different methods for protecting the spinal cord against experimental ischemic injury. Therefore, the authors compared the protective effects of thiopental with those of hypothermia (35 degrees Celsius and 32 degrees Celsius) on hindlimb motor functions and histopathology after transient spinal cord ischemia. Methods: Twenty‐seven New Zealand white rabbits were assigned to one of the four groups: a thiopental‐normothermia group (burst‐suppression dose of thiopental; esophageal temperature = 38 degrees Celsius; n = 7), a halothane‐mild hypothermia group (halothane, 1%; esophageal temperature = 35 degrees Celsius; n = 7), a halothane‐moderate hypothermia group (halothane, 1%; esophageal temperature = 32 degrees Celsius; n = 6), and a halothane‐normothermia group (halothane, 1%; esophageal temperature = 38 degrees Celsius; n = 7). The animals were then subjected to 20 min of spinal cord ischemia produced by occlusion of the aorta distal to the origin of left renal artery. Hindlimb motor function was observed for 48 h after reperfusion. Histopathology of the lumbar spinal cord also was examined. Results: All animals in the halothane‐mild hypothermia and halothane‐moderate hypothermia groups were neurologically normal 48 h after ischemia. There was no statistical difference in the final neurologic status and histopathology between the thiopental‐normothermia and halothane‐normothermia groups. However, the final neurologic status and histopathology in both groups were worse than in the halothane‐mild hypothermia or halothane‐moderate hypothermia groups. There was a strong correlation between the final neurologic status and the numbers of normal neurons in the anterior spinal cord. Conclusions: These results suggest that mild and moderate hypothermia protects against ischemic spinal cord injury in rabbits, and a burst‐suppression dose of thiopental does not offer any advantage over halothane.

Effect of ibuprofen on regional eicosanoid production and neuronal injury after forebrain ischemia in rats

Post-ischemic metabolism of arachidonic acid by cyclooxygenase results in the elaboration of numerous eicosanoids and in the generation of free radicals. Accordingly, the effect of cyclooxygenase inhibition by ibuprofen on post-ischemic eicosanoid production and delayed neuronal death was evaluated in Wistar-Kyoto rats subjected to incomplete forebrain ischemia. In control (C) and ibuprofen-treated groups (n = 5 each), pre- and post-ischemic eicosanoid production in the caudate nucleus (CN) and dorsal hippocampus (HPC) were evaluated by microdialysis. The ibuprofen-treated animals were given ibuprofen, 15 mg/kg i.v., prior to insertion of microdialysis probes. Forebrain ischemia was induced by bilateral carotid artery occlusion (BCAO) for 10 min with simultaneous hypotension to 35 Torr. The concentrations of thromboxane B2 (TxB2), 6-keto-PGF1 alpha and PGF2 alpha in the microdialysate were measured by radioimmunoassay. In two additional concurrent groups of rats (n = 10 each), neuronal injury in the HPC, CN and cortex (parietal, temporal and entorhinal regions) was evaluated histologically three days after 10 min of forebrain ischemia with and without pre-ischemic ibuprofen administration. In the control microdialysis group, levels of TxB2, 6-keto-PGF1 alpha and PGF2 alpha increased in both CN and HPC after probe insertion. These probe related increases were substantially reduced in the ibuprofen group. After ischemia and reperfusion in the control group, the levels of TxB2 and PGF2 alpha increased in both CN and HPC. Levels of 6-keto-PGF1 alpha increased in the CN but not in the HPC. The administration of ibuprofen substantially reduced post-ischemic TxB2 and PGF2 alpha levels in both CN and HPC and decreased 6-keto-PGF1 alpha levels in the CN. The results of these initial microdialysis studies left the possibility that, in the ibuprofen group, the reduction in eicosanoid levels after probe penetration might have influenced the subsequent post-ischemic eicosanoid production. Therefore, in an additional group of animals (n = 5), ibuprofen was administered after probe insertion. Only PGF2 alpha levels were measured in this group. Increased levels of PGF2 alpha comparable to the original control group were detected after probe penetration. Nonetheless, after ibuprofen administration, the pre- and post-ischemic levels of PGF2 alpha were again significantly reduced. In the histologic evaluation groups, overall neuronal injury was significantly less in the ibuprofen treated animals. This protective effect of ibuprofen was most clearly evident in the CA3 sector of the HPC.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of droperidol, pentobarbital, and ketamine on myogenic transcranial magnetic motor-evoked responses in humans

Myogenic motor-evoked responses to transcranial magnetic stimulation of the motor cortex (tcmag-MERs) may become clinically useful for the noninvasive assessment of motor pathway conduction during surgery. However, application is hindered because most anesthetic regimens result in severe depression of tcmag-MER amplitudes. As part of our systematic attempts to identify anesthetic agents and supplements suitable for use during tcmag-MER recording, we studied the effect of bolus doses of pentobarbital (1.5 mg/kg), droperidol (0.07 mg/kg), or ketamine (1 mg/kg), administered intravenously, on compound muscle action potentials to transcranial magnetic stimulation in five healthy volunteers. The doses were chosen to be comparable with doses that might be suitable for supplementation of a nitrous oxide/opioid anesthetic technique. Droperidol administration resulted in sustained amplitude depression of both tibialis and adductor pollicis tc-MERs to 30 +/- 9% and 39 +/- 14% of baseline (P < 0.01). Tcmag-MER amplitude changes after pentobarbital were variable, ranging from no change to substantial amplitude depression (to 20% of baseline) in two subjects. In contrast, ketamine administration did not result in significant amplitude depression. In three subjects, tibialis anterior amplitude increased to 150 to 220% of control values in the first 10 minutes after ketamine. Onset latency was unchanged after any drug. These data indicate that tcmag-MERs are moderately depressed after droperidol and pentobarbital but well preserved after ketamine. Ketamine may be a more suitable supplement to opioid/nitrous oxide anesthesia than droperidol or pentobarbital.

A Comparison of the Cerebral Protective Effects of Etomidate, Thiopental, and Isoflurane in a Model of Forebrain Ischemia in the Rat

We evaluated the effect of etomidate, thiopental, and isoflurane on ischemic neuronal injury in rats. Control group animals received 1.2% isoflurane. The animals in the etomidate and thiopental groups received an infusion of either etomidate or thiopental until electroencephalographic (EEG) burst-suppression was attained. In the fourth group, the isoflurane concentration was increased to 3% (sufficient to produce EEG burst-suppression). Forebrain ischemia was induced by bilateral carotid artery occlusion with simultaneous hypotension for 10 min. Three days after ischemia, two blinded observers evaluated neuronal injury in coronal brain sections stained with hematoxylin and eosin. Injury to the ventral CA1 of the hippocampus was less in the etomidate group than in the control group. Injury to the entorhinal cortex was less in the thiopental group than in the control group. Histopathologic outcome in animals anesthetized with 1.2% isoflurane and 3% isoflurane was not different. Although these data indicate that etomidate and thiopental might reduce ischemic injury in some structures, the magnitude of the protective effects observed was small.

Combined therapy with dizocilpine and levemopamil does not reduce ischemic neuronal injury in rats.

Excessive intracellular accumulation of calcium has been postulated to result in ischemic neuronal death. Reduction of intracellular calcium entry should therefore be expected to reduce ischemic neuronal injury. Two pathways through which extracellular calcium ions can enter neurons are voltage-sensitive and N-methyl-D-aspartate receptor-linked cation pores. Combined blockade of both these types of channels might be more effective in reducing intracellular calcium accumulation than the blockade of either channel alone. We therefore evaluated the cerebroprotective effects of dizocilpine, an N-methyl-D-aspartate receptor antagonist, and levemopamil, a phenylalkylamine calcium channel blocker, administered singly or in combination, in a model of forebrain ischemia in the rat. Four groups of rats (n = 8 each) were studied. In the first group, dizocilpine, 5 mg/kg, was administered before ischemia. In the second group, levemopamil, 5 mg/kg, was given both preischemia and 2 h postischemia. In the third group, both dizocilpine (5 mg/kg) and levemopamil (5 mg/kg) were given preischemia and levemopamil (5 mg/kg) was given postischemia. The control group received saline placebo. The rats were subjected to forebrain ischemia by bilateral carotid artery occlusion for 10 min with simultaneous hypotension to 35 mm Hg. Neuronal injury was evaluated 3 days after ischemia. Dizocilpine reduced postischemia neuronal injury in the ventral hippocampus (p = 0.045). Levemopamil and the combination of levemopamil and dizocilpine did not protect neurons from ischemic injury. The present study does not provide support for the strategy of combined therapy with dizocilpine (administered before ischemia) and levemopamil (administered before and after ischemia) to protect neurons from injury produced by severe incomplete forebrain ischemia.

A COMPARISON OF THE CEREBRAL PROTECTIVE EFFECTS OF ISOFLURANE AND MILD HYPOTHERMIA IN A MODEL OF INCOMPLETE FOREBRAIN ISCHEMIA

&NA; No abstract available.