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Biomedical subjects

M Morio

Publications and source records attributed to M Morio.

At least 37 records · Page 2Linked to original sources
PubMed1990

The association of halothane-induced lipid peroxidation with the anaerobic metabolism of halothane: an in vitro study in guinea pig liver microsomes.

The formation of pentane and anaerobic metabolites of halothane (2-chloro-1,1,1-trifluoroethane and 2-chloro-1,1-difluoroethylene) in a mixture of guinea pig liver microsomes and halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) in the presence of NADPH was studied by gas chromatography. Under anaerobic conditions, pentane was formed without halothane and was inhibited by oxygen tension. This anaerobic pentane formation was potentiated 2.5 times by addition of halothane. Halothane-induced pentane formation increased dose-dependently with a halothane concentration of up to 2.1 mmol/liter and then decreased in the presence of increasing concentrations of halothane. Inhibition by a higher substrate was also observed in the formation of anaerobic metabolites of halothane. Antioxidant agents, vitamin E and glutathione, reduced the pentane formation, but did not reduce the anaerobic metabolites of halothane. Metyrapone, an inhibitor of cytochrome P-450, reduced both the pentane and anaerobic metabolites of halothane. These results show halothane-induced lipid peroxidation in association with the anaerobic metabolism of halothane in guinea pig liver microsomes.

Anaerobiosis↗
PubMed1989

Halothane-induced hepatic microsomal lipid peroxidation in guinea pigs and rats.

Halothane-induced hepatic microsomal lipid peroxidation in guinea pigs and rats was examined with respect to the mixed function oxidase system, anaerobic dehalogenation activity of halothane, and the antioxidant system. The levels of cytochrome P-450 and NADPH-cytochrome P-450 reductase were significantly higher in guinea pigs than in rats. There was no difference between the two animals in anaerobic dehalogenation activity of halothane per cytochrome P-450 in microsomes. Microsomal alpha-tocopherol was significantly lower in guinea pigs than in rats, and was increased by multiple exposure to halothane in guinea pigs but remained lower than in rats. Microsomal alpha-tocopherol was decreased in rats by multiple exposure. The concentration of reduced glutathione and ascorbic acid was decreased significantly by multiple exposure to halothane in guinea pigs but not in rats. These results suggest that the higher level of halothane-induced hepatic microsomal lipid peroxidation in guinea pigs is due to the large production of radical metabolites resulting from the large amounts of cytochrome P-450, the high activity of NADPH-cytochrome P-450 reductase, and the low concentration of microsomal alpha-tocopherol.

Animals↗
PubMed1989

The effects of vasoactive drugs on halothane inhibition of contractions of rat mesenteric lymphatics.

The effects of halothane on alpha-adrenergic receptors, beta-adrenergic receptors, and the process of Ca++ dependent contractions on rat mesenteric lymphatics were examined. Halothane depressed the contraction rate of mesenteric lymphatics but did not effect the increase in lymphatic contraction rate caused by noradrenaline (an alpha-agonist). The depressant effect of halothane on the contraction rate was also not antagonized by propranolol (a beta-blocker), but was partly reversed by CaCl2. These findings suggest that the depressant effect of halothane on the lymphatic contraction rate derives not from blocking lymphatic alpha-receptors or stimulating lymphatic beta-receptors but rather by halothane inhibition on the process of Ca++ dependent lymphatic contractions.

Animals↗
PubMed1989

Pentane as an index of in vitro lipid peroxidation via microsomal NADPH-P-450 enzyme systems.

Pentane was measured in a mixture of guinea pig liver microsomes and carbontetrachloride (CCl4) in the presence of nicotineamide adenine dinucleotide phosphate (NADPH) and under anaerobic conditions by gas chromatography. Pentane of 0.2 pmol/mg protein/min was formed in the presence of NADPH without CCl4. Pentane formation increased to 2.0 pmol/mg protein/min in the presence of CCl4 and NADPH. This reaction required an anaerobic atmosphere, 2.1 mmol/litter of NADPH and 13.4 mmol/litter of CCl4 under optimal conditions. The formation was reduced in the presence of oxygen, glutathione, vitamin E and metyrapone. These results clearly show that pentane is formed by lipid peroxidation initiated by the free radical cleavage products of CCl4, which are anaerobically produced by NADPH-dependent microsomal enzymes. We conclude that pentane is a good index of in vitro lipid peroxidation via microsomal NADPH-P-450 enzyme systems.

Animals↗
PubMed1989

[Influence of cardiopulmonary bypass on plasma lipid peroxides].

In 22 patients who underwent cardiac surgery with cardiopulmonary bypass (CPB), we studied the influence of CPB on the level of lipid peroxides (LPO) in plasma by means of measuring the time course of plasma LPO level during and after CPB. We expressed LPO level, which was measured by thiobarbituric acid reaction, as the level of malondialdehyde. In our preliminary study, it was found necessary to correct the plasma LPO level diluted by priming fluids of CPB machine and the concentration of plasma protein was fitted for its correction. In the following study, we used the plasma LPO level corrected by the concentration of plasma protein. LPO were significantly decreased since the initiation of CPB (1.669 +/- 0.208 versus pre-CPB 1.785 +/- 0.158 log nmol MDA/gm protein, p less than 0.05) to the post CPB 30 minutes, except around 60 minutes after initiation of CPB (1.735 +/- 0.242 log nmol MDA/gm protein, p greater than 0.05). As the initial change (the values at 30 minutes after CPB initiation) may express the effect of CPB directly in this time course of LPO, we analyzed the initial change on different background factors. By ordinary analysis of the initial change, as to the effect of type of disease (congenital and acquired), LPO were decreased in the acquired group (1.617 +/- 0.197 versus pre-CPB 1.779 +/- 0.163 log nmol MDA/gm protein, p less than 0.05). At that time the acquired group was significantly different from the congenital group (1.799 +/- 0.191 versus pre-CPB 1.800 +/- 0.157 log nmol MDA/gm protein, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Inhibitory effect of paraquat on biotransformation of halothane in rabbit liver microsomes.

Microsomal fractions were prepared from the liver of rabbits to investigate the effects of paraquat (methyl viologen) on generation of metabolites of halothane under the optimal aerobic and anaerobic conditions. Halothane (CF3CHClBr) is known to undergo oxidative and reductive biotransformation in the hepatic mixed function oxidase system including cytochrome-P450 reductase and cytochrome P450. The results showed that paraquat inhibited generation of metabolites of halothane under these conditions. Generation of the aerobic metabolite, trifluoroacetic acid (CF3COOH), and anaerobic metabolites, 2-chloro-1, 1, 1-trifluoroethane (CF3CH2Cl) and 2-chloro-1, 1-difluoroethylene (CF2CHCl), were inhibited 50% by 4.96 mM and 35.3 mM paraquat, respectively. Possible mechanisms were speculated on to account for the inhibitory effects: one being the impaired formation of halothane-cytochrome P450 complex by addition of paraquat, and the other the diversion of electrons from cytochrome-P-450 reductase to generate active paraquat radicals. It is concluded that paraquat inhibits NADPH-dependent biotransformation of halothane catalyzed in mixed function oxidase system.

Animals↗
PubMed1989

[Comparative study of in vitro diagnosis by the skinned fiber test and clinical diagnosis of malignant hyperthermia].

Skeletal muscles from twenty patients suspected of malignant hyperthermia during general anesthesia were examined with the skinned fiber test for abnormality in the Ca2+ release function of their sarcoplasmic reticulum, and the result was correlated with the classifications of the patients in accordance with the clinical criteria now used in Japan. Among them, fourteen patients were diagnosed as clinical malignant hyperthermia syndrome (fulminant syndrome: 4, abortive syndrome: 10). Three out of four fulminant cases showed potentiated Ca-induced Ca release mechanism of the sarcoplasmic reticulum in their skeletal muscles. The others including six patients not diagnosed as malignant hyperthermia were normal in the sarcoplasmic reticulum function. This suggests that the skinned fiber test has comparatively high sensitivity to fulminant malignant hyperthermia syndrome. The present paper discusses, based on the present results, the problems resulting from the difference in diagnostic concept between in vitro criteria by the skinned fiber test to detect a specific pathogenetical factor in the skeletal muscle of a single abnormality and clinical criteria to pick up a series of relatively non-specific symptoms and signs of a clinical syndrome.

Adolescent↗
PubMed1989

Determination by ion-exchange chromatography of trifluoroacetic acid as a biliary metabolite of isoflurane in the rabbit.

The optimal composition of eluant for trifluoroacetic acid (TFAA) analysis by ion-exchange chromatography was determined and a preliminary study to detect TFAA, a metabolite of isoflurane, in bile of rabbits during and after inhalation of isoflurane was made. The optimal composition of eluant for TFAA analysis by ion-exchange chromatography was determined to be a solution of 2mM Na2CO3 and 4mM NaHCO3. Rabbits were divided into 4 groups; A group: 1 hr inhalation of 2% isoflurane, B group: 2 hr inhalation of 2% isoflurane, C group: 2 hr inhalation of 3% isoflurane, and D group: 2 hr inhalation of 4% isoflurane. The maximum biliary TFAA concentration in groups A, B, C and D averaged 17.5 +/- 1.4 microM (mean +/- S.D.) at 105 min, 37.1 +/- 11.5 microM at 315 min, 54.5 +/- 9.4 microM at 585 min and 34.4 +/- 12.1 microM at 555 min after termination of inhalation. Cumulative excreted amounts of biliary TFAA for 20 hours were 746 nmols in A group (8 hours), 3,421 nmols in B group, 6,582 nmols in C group and 3,267 nmols in D group. Half-lives of biliary excreted TFAA were 63 min, 325 min, 478 min and 546 min, respectively. These results showed that ion-exchange chromatography is more convenient for detecting TFAA as a metabolite of isoflurane than isotachophoresis, gas chromatography, paper chromatography and thin layer chromatography and that TFAA was determined as a biliary metabolite of isoflurane in the rabbit.

Animals↗
PubMed1989

Effect of halothane anesthesia on mesenteric intralymphatic pressure in the rat.

The effect of halothane on mesenteric intralymphatic pressure was examined in 20 rats. Following administration of 1.5% halothane, lymph pressure decreased from a control value of 7.6 +/- 1.5cmH20 to 3.8 +/- 1.8cmH20. On the other hand, a lower concentration of halothane (1%) did not alter lymph pressure. In conjunction with earlier findings, these data suggest further that lymph propulsion is suppressed during halothane (greater than 1.5%) anesthesia.

Anesthesia, Inhalation↗
PubMed1988

[Hypothalamic pituitary function in brain death patients--from blood pituitary hormones and hypothalamic hormones].

According to the report of the Health and Welfare Ministry's research committee on brain death (1985), "brain death is defined as an irreversible cessation of the total brain function including brain stem." However, in brain death patients, whether the hypothalamic function which belongs to the brain stem function has completely ceased or not is unknown. In order to evaluate the hypothalamic function in brain death patients, the blood levels of the pituitary hormones and hypothalamic hormones were measured, and anterior pituitary stimulation test with triple bolus injection (TRH 500 micrograms, LH-RH 100 micrograms, regular insulin 0.3-0.7 unit/kg) was performed. The subjects were 13 brain death patients whose clinical states fully satisfied the criteria proposed by the committee. 1) The average blood levels of anterior pituitary hormones in these brain death patients were within normal range, and that of growth hormone was more than the twice of the normal level. 2) The blood anterior pituitary hormones were detectable in almost all cases even several days after the diagnosis of the brain death. 3) LH reserve was maintained in three cases. FSH reserve was maintained in three cases. Prolactin reserve was maintained in two cases. TSH reserve was maintained in one case. 4) Blood ADH (antidiuretic hormones) were detectable in 7 cases out of 9 cases. The blood ADH level of one case, in particular, was rather high (above 10 pg/ml). 5) Histopathologically anterior pituitaries were examined in three autopsy cases. The central necrotic areas were observed in all cases, but normal pituitary tissues existed peripherally. And all anterior pituitary hormones could be recognized immunohistochemically. 6) The blood levels of the hypothalamic hormones (GRF, CRF, LH-RH) were measured in four cases. The hypothalamic hormones were detectable in all cases. In one case, the levels of GRF were within normal range even 9 or 15 days after the diagnosis of brain death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Halothane-induced liver injury as a consequence of enhanced microsomal lipid peroxidation in guinea pigs.

We investigated the role of microsomal lipid peroxidation in halothane hepatotoxicity in guinea pigs. Animals were exposed to halothane, isoflurane or enflurane. Enhancement of microsomal lipid peroxidation was specific to halothane. The time-course of lipid peroxidation and hepatic damage following a single exposure to halothane was investigated by measuring the thiobarbituric acid (TBA)reactive products, serum transaminase activity, reduced glutathione (GSH) concentration and histopathological examination. Microsomal lipid peroxidation was enhanced most rapidly and preceded GSH depletion and hepatic injury. Metyrapone, an inhibitor of cytochrome P-450, and N-tert-butyl-alpha-phenylnitrone (BPN), a radical trapping agent, inhibited halothane-induced lipid peroxidation and the incidence and severity of liver injury. The metabolism of halothane was considered to be inhibited by metyrapone and the reactivity of radical intermediates was considered to be decreased by BPN. Microsomal lipid peroxidation was initiated by radical metabolites of halothane but did not result from GSH depletion. Inhibition of microsomal lipid peroxidation reduced the halothane hepatotoxicity. These results demonstrated that the halothane-induced liver injury was caused by microsomal lipid peroxidation in guinea pigs.

Administration, Inhalation↗
PubMed1988

Halothane-induced changes in contractions of mesenteric lymphatics of the rat.

The effects of halothane on the contraction of mesenteric lymphatics was examined in rats. Following administration of 0.75% or 1.5% halothane, the contraction rate decreased from 10.6 +/- 3.1 to 7.4 +/- 2.5 times/minute and from 13.8 +/- 3.9 to 4.1 +/- 3.5 times/minute, respectively. Halothane caused a dose-dependent suppression of contractile movements of the mesenteric lymphatics.

Animals↗
PubMed1988

Biotransformation of isoflurane: urinary and serum fluoride ion and organic fluorine.

The serum and urinary concentrations of fluorinated metabolites of isoflurane after inhalation of three different concentrations of isoflurane were studied in 18 ASA physical status 1 or 2 patients, scheduled for orthopedic or otolaryngeal surgery. Isoflurane was administered for 60 min during fentanyl-nitrous oxide-oxygen, and its end-tidal concentration was maintained at 0.3, 0.6, or 1.15% (groups I, II, and III). The organic fluorine was determined by combustion and fluoride ions were analyzed by ion chromatography. The amounts were expressed in terms of fluoride ion. The concentrations of serum fluoride ion and organic fluorine increased significantly 15 min after the onset of inhalation of isoflurane. The mean peak values of fluoride ions were 3.8 +/- 1.1, 3.9 +/- 1.4, and 4.2 +/- 0.9 mumole/1 (M +/- SD) in patients in groups I, II, and III, respectively. The half-lives of fluoride ion and of organic fluorine as metabolites of isoflurane, calculated from the amounts excreted in urine, were 36 h and 41 h, respectively. The cumulative amounts of fluoride ion and organic fluorine excreted up to the 6th postoperative day were 548 +/- 230 and 785 +/- 452 mumoles in group I, 594 +/- 138 and 1,378 +/- 807 mumoles in group II, and 1,032 +/- 496 and 728 +/- 265 mumoles (M +/- SD) in group III, respectively. The urinary excreted fluoride ion increased in proportion to the dose of isoflurane and approximately 1.3 mmol was excreted per 1 MAC X hour inhalation of isoflurane. The authors concluded that isoflurane might be biotransformed to a greater extent than reported previously, although the serum fluoride ion level was found to be low.

Adult↗