Effect of isoflurane on the dechlorination of carbon tetrachloride to chloroform was investigated in the guinea-pig liver microsomes. Under anaerobic conditions, chloroform is produced from carbon tetrachloride through the microsomes in the presence of NADPH, and such production of chloroform was increased by the addition of isoflurane. The K(m) for the production of chloroform from carbon tetrachloride was decreased to 86% by isoflurane compared with the control; however the maximum velocity of chloroform production was also decreased to 50%. The formation of the 445 nm band in the mixture of reduced cytochrome P-450 and carbon tetrachloride, and cytochrome P-450 reduction by NADPH were both accelerated by isoflurane, without alteration of NADPH-cytochrome c reductase activity. These results indicate that trichloromethyl radical, an intermediate product of carbon tetrachloride, easily combines to the haeme part of cytochrome P-450, whereas the protein part combines to isoflurane after being reduced by NADPH, which results in acceleration of carbon tetrachloride dechlorination under a lower concentration of carbon tetrachloride. These results may have implications for other drugs that are administered during isoflurane anaesthesia.

Animals↗

PubMedDate not supplied

Contrasting effect of isoflurane on drug metabolism: decreased type I and increased type II substrate metabolism in guinea pig liver microsomes.

Inhalation anaesthetics might affect perioperative drug elimination by altering drug distribution, hepatic blood flow or drug metabolism. The in vitro effects of isoflurane on aniline hydroxylation and aminopyrine N-demethylation were investigated with guinea pig liver microsomes to assess the role of isoflurane on oxidative drug metabolism through the hepatic mixed-function oxidase system. p-Aminophenol and formaldehyde were measured spectrophotometrically as metabolic products of aniline hydroxylation and aminopyrine N-demethylation, respectively, where the reaction mixture consisted of a microsomal suspension, NADPH, aminopyrine or aniline, with or without isoflurane. The rate of cytochrome P-450 reduction by NADPH affected in the presence of isoflurane was investigated by spectrometric measurement of the CO-cytochrome P-450 complex formation at various times. Due to the addition of isoflurane, the Vmax values for aniline hydroxylation evidently increased except in high isoflurane concentration (3.33 mM) and for aminopyrine N-demethylation the value was significantly low only in the presence of a high isoflurane concentration, whereas the K(m) values significantly decreased in aniline hydroxylation and increased in aminopyrine N-demethylation, and isoflurane also accelerated the rate of cytochrome P-450 reduction by NADPH. These results reflect the inhibition of aminopyrine N-demethylation and activation of aniline hydroxylation in the presence of isoflurane as a consequence of isoflurane-accelerated cytochrome P-450 reduction by NADPH and/or drug-enzyme binding properties, and may have implications on the metabolism of perioperatively administered drugs during isoflurane anaesthesia.

Aminopyrine N-Demethylase↗

PubMedDate not supplied

Inhibitory effect of gomisi on reductive metabolism of halothane.

The effect of Gomisi (dried ripe fruit of schizandra chinensis) on chlorodifluoroethylene (CDE) and chlorotrifluoroethane (CTE) formation was investigated. The incubation mixtures for the measurement of reductive metabolites of halothane consisted of liver microsomal suspensions, 3 mM NADPH, extract solution of Gomisi and halothane in 0.1 M potassium phosphate buffer (pH 7.4). The production of CDE and CTE was inhibited by Gomisi in a dose-dependent way. The production were reduced to half in the presence of 0.5% Gomisi extract in the reaction mixture. The results suggest that Gomisi can inhibit the reductive metabolism of halothane in vitro; thus it may protect against halothane-induced hepatitis.

Animals↗

PubMedDate not supplied

Isoflurane increases the anaerobic metabolites of halothane.

The effect of isoflurane on the anaerobic metabolism of halothane to chlorodifluoroethene (CDE) and chlorotrifluoroethane (CTE) was studied with microsomes of guinea pig liver by gas chromatography. The reaction mixture used to measure the end products of anaerobic metabolism consisted of a microsomal suspension, 3 mM NADPH, halothane and isoflurane (except in control groups) in 0.1 M potassium phosphate buffer solution (pH 7.4). The Km values for CDE formation were 601.61 +/- 266.91, 254.22 +/- 86.58, 257.92 +/- 129.11, 268.55 +/- 125.66 and 319.22 +/- 86.76 microM (mean +/- SD, n = 5) at 0 mM (0%), 0.12 mM (0.26%), 0.29 mM (0.64%), 0.58 mM (1.30%) and 1.16 mM (2.59%) isoflurane, respectively. The Km values for CTE formation were 1204.74 +/- 551.64, 553.75 +/- 177.89, 521.14 +/- 249.77, 560.67 +/- 229.61 and 711.05 +/- 317.13 microM (n = 5) at 0 mM (0%), 0.12 mM (0.26%), 0.29 mM (0.64%), 0.58 mM (1.30%) and 1.16 mM (2.59%) isoflurane, respectively. In contrast, the Vmax values for CDE and CTE formation at these isoflurane concentrations were not significantly different than in the control groups. In this study the production of CDE and CTE was significantly (P < 0.05) increased by isoflurane, at concentrations up to 0.58 mM (1.30%).

Anaerobiosis↗

PubMedDate not supplied

Origin and distribution of brain-stem somatosensory evoked potentials in humans.

The distribution of somatosensory evoked potentials (SEPs) recorded from the brain-stem surface was studied to investigate their generator sources in 14 patients during surgical exploration of the posterior fossa. Two distinct SEPs of different morphologies and electrical orientation were obtained by median nerve stimulation. A small positive-large negative-late prolonged positive wave was recorded from the cuneate nucleus and its vicinity. There was a phase-reversal between the cuneate nucleus and the ventral surface of the medulla, depicting a dipole for dorso-ventral organization. From the pons and midbrain, triphasic waves with predominant negativity were obtained. This type of SEP had identical wave forms between the dorsal, lateral and ventral surface of the pons and midbrain. It showed an increase in negative peak latency as the recording sites moved rostrally, suggesting an ascending axial orientation. In a patient with pontine hemorrhage, the killed end potential, a large monophasic positive potential was obtained from the lesion. This potential occurs when an impulse approaches but never passes beyond the recording electrode. Therefore, the triphasic SEP from the pons and midbrain reflects an axonal potential generated in the medial lemniscal pathway.

Adolescent↗

PubMedDate not supplied

Discrepancy between SEPs directly recorded from the dorsal column nuclei following upper and lower limb stimulation in patients with syringomyelia.

Somatosensory evoked potentials (SEPs) in response to electrical stimulation of the median nerve (MN) and posterior tibial nerve (PTN) were studied in 2 patients with syringomyelia. Intraoperative recordings were made from the surface of the dorsal column nuclei as well as from the scalp. Following MN stimulation, there was a preservation of scalp-recorded P9, P11, P13, and N20, however, there was an absence of spinal N13-P13. The dorsal column SEPs to MN stimulation were normal, characterized by a major negativity (N1), preceded by a small positivity (P1) and followed by a large positivity (P2). On the other hand, there was little or no cortical response (P37) to PTN stimulation. The dorsal column SEPs to PTN stimulation showed a disappearance of the normal P1'-N1'-P2' configuration, being replaced by a series of small spiky waves. The syringomyelic cavity may have thus compressed the gracile dorsal column which courses more medially than the cuneate pathway, causing desynchronization of the dorsal column SEPs. These findings suggest that dorsal column pathway arising from the lower limb is more vulnerable than that from the upper limb when a cervical syrinx is present.

Adult↗

PubMedDate not supplied

Intradural spinal meningioma in a 5-year-old female.

The case of a 5-year-old female with an intradural spinal meningioma is presented. She showed slowly progressive muscle weakness of the lower extremities commencing at 3 years. Spinal magnetic resonance imaging (MRI) demonstrated an intradural mass extending from the eleventh thoracic vertebra to the fifth lumbar vertebra, which was excised totally by means of laminoplasty. The surgical procedure brought a gradual improvement in her gait. This case is unusual because of the tumor's location (lumbar) and origin (cauda equina), and because of the onset at a relatively young age.

Child, Preschool↗