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Biomedical subjects

C W Loomis

Publications and source records attributed to C W Loomis.

At least 37 records · Page 2Linked to original sources
PubMed1986

Arterial isoflurane concentration and EEG burst suppression during cardiopulmonary bypass.

Isoflurane (1.5 to 3.0 vol% in oxygen) was used to control intraoperative hypertension in 10 patients undergoing hypothermic cardiopulmonary bypass surgery. Isoflurane was administered through the membrane oxygenator of the bypass pump and yielded plateau concentrations in arterial blood ranging from 36.6 to 84.4 micrograms/ml (0.5 and 1.16 vol%, respectively). Isoflurane dosing resulted in prolonged periods (21 to 63 minutes) of EEG burst suppression and isoelectric activity in nine patients. Burst suppression was not a result of hypothermia. There was a close temporal relationship between isoflurane concentration and the onset of burst suppression (mean onset time: 27.3 +/- 4.56 minutes after isoflurane begun). The mean arterial isoflurane concentration at the onset of burst suppression was 46.5 +/- 10.7 micrograms/ml; the nasopharyngeal temperature was 26.0 degrees +/- 0.61 degrees C. Isoflurane was eliminated rapidly from blood with a mean apparent t1/2 of 18.8 +/- 5.46 minutes.

Adult↗
PubMed1985

A comparative study of the inhibition of hepatic aldehyde dehydrogenases in the rat by methyltetrazolethiol, calcium carbimide, and disulfiram.

Methyltetrazolethiol (1-methyl-5-mercapto-1,2,3,4-tetrazole, MTT) is a heterocyclic substituent of the cephalosporin antibiotics, cefamandole, cefoperazone, and moxalactam. Pretreatment of rats with MTT has been reported to increase blood acetaldehyde concentration after ethanol administration. The time course of MTT-induced inhibition of hepatic aldehyde dehydrogenases (ALDH) was determined in adult, male Sprague-Dawley rats in comparison with the hepatic ALDH inhibition induced by calcium carbimide (calcium cyanamide, CC) and disulfiram (D). The apparent onset of maximal inhibition of hepatic low Km ALDH occurred at 2 h for 50 mg/kg MTT (subcutaneous, s.c.) and 7 mg/kg CC (oral) and at 24 h for 300 mg/kg D (oral). The relative magnitude of maximal inhibition of low Km ALDH was CC greater than D greater than MTT. The relative duration of enzyme inhibition was D greater than MTT greater than CC. High Km ALDH was only inhibited by CC. Hepatic low Km ALDH was selectively inhibited by s.c. and oral administration of 125 mg/kg MTT. For s.c. administration of 125 mg/kg MTT, the magnitude of maximal enzyme inhibition and the duration of inhibition were greater than for the 50 mg/kg dose. Oral administration of 125 mg/kg MTT produced similar inhibition of hepatic low Km ALDH compared with s.c. administration of the same dose. The time course of blood ethanol and acetaldehyde concentrations was determined for the intravenous infusion of two 0.3-g/kg doses of ethanol to rats that were pretreated orally with saline (1 h), MTT (125 mg/kg, 2 h), or CC (7 mg/kg, 1 h). The relative increase in blood acetaldehyde concentration compared with saline pretreatment was CC greater than MTT. The elimination of ethanol from blood was slower in the MTT- and CC-pretreated animals, and this effect was more pronounced for CC pretreatment. Overall, the data demonstrate that the characteristics of hepatic ALDH inhibition for MTT are different from those of the known ALDH inhibitors, CC and D.

Acetaldehyde↗
PubMed1985

Analgesia and autonomic function following intrathecal administration of morphine and norepinephrine to the rat.

The acute intrathecal (i.t.) administration of 10, 25, 50, and 100 microgram morphine and 7.5, 10, 15, and 30 microgram (-)norepinephrine (NE) to the rat produced dose-dependent, long-lasting analgesia as assessed by the tail-flick and hot-plate tests. For i.t. morphine, maximum analgesia was observed 30-60 min after drug administration. The duration of analgesia in the tail-flick test ranged from 30 to 150 min; the duration of analgesia in the hot-plate test ranged from 60 to 120 min. For i.t. NE, maximum analgesia was observed 15-60 min after drug infusion. The duration of NE-induced analgesia in the hot-plate test ranged from 45 to 120 min and was 120 min in the tail-flick test. The effects of acute i.t. and intravenous (i.v.) infusions of morphine (10 microgram) and NE (15 microgram) on heart rate, blood pressure, arterial pH, partial pressure of oxygen (Po2), partial pressure of carbon dioxide (Pco2), and standard bicarbonate were determined over 45 min in rats anesthetized with alpha-chloralose (70 mg/kg). Morphine significantly decreased Po2 throughout the experiment but did not affect blood pressure, heart rate, pH, Pco2 and standard bicarbonate. A significant increase in blood pressure (137% of control) was observed 2.5 min after i.t. administration of NE. Intravenous NE produced a marked increase in blood pressure (246% of control) followed by a compensatory decrease in heart rate. There were no significant changes in blood gases with i.t. and i.v. NE. The data suggest that i.t. morphine and NE can produce effective analgesia with minimal effects on cardiovascular and respiratory function.

Analgesia↗
PubMed1984

Decrease in calcium carbimide (calcium cyanamide)-induced inhibition of rat hepatic aldehyde dehydrogenases by multiple ethanol administration.

Ethanol (0.3 g/kg) was administered intravenously to adult, male rats at 3 h or at 1 and 3 h after gastric intubation of 7 mg/kg calcium carbimide (CC). For animals administered CC and two ethanol doses, blood ethanol concentration was similar for the two doses; however, blood acetaldehyde concentration was significantly less for the second ethanol dose compared with the first dose as determined by the area-under-curve data. Hepatic aldehyde dehydrogenase activity was determined over the 3.5- to 5-h interval after CC pretreatment. The inhibition of low Km and high Km aldehyde dehydrogenase activity in liver homogenate and in hepatic mitochondrial, cytosolic, and microsomal fractions was significantly less for rats administered CC followed by two ethanol doses compared with that for animals administered CC alone or CC followed by one ethanol dose. The data demonstrate that increased acetaldehyde concentration, produced during the CC - ethanol interaction, can augment the recovery of hepatic aldehyde dehydrogenase activity following CC pretreatment and indicate the existence of a displaceable enzyme inhibitor derived from CC.

Acetaldehyde↗
PubMed1983

Disposition of ethanol in human maternal venous blood and amniotic fluid.

The disposition of ethanol and acetaldehyde in maternal venous blood and amniotic fluid was studied over 3.5 hours following the ingestion of 0.3 gm/kg of ethanol by six healthy pregnant women at 16 to 18 weeks' gestation. There was a time lag in the appearance of ethanol in amniotic fluid compared with its appearance in maternal venous blood. The maximum maternal venous blood ethanol concentration was twice the maximum amniotic fluid ethanol concentration and occurred at an earlier time. At 3.5 hours, ethanol was present in amniotic fluid, whereas there was virtually no measurable ethanol in maternal venous blood. The rate of ethanol elimination from amniotic fluid was about half the elimination rate from maternal venous blood. Acetaldehyde was present in the maternal venous blood of four subjects, and the maximum acetaldehyde concentration occurred at about the same time as the maximum maternal venous blood ethanol concentration. Acetaldehyde was found in the amniotic fluid of one of these four subjects, and the acetaldehyde concentration was greater in amniotic fluid than in maternal venous blood. It is proposed that the amniotic fluid may act as a reservoir for ethanol following maternal ingestion such that the fetus would be exposed to ethanol for a longer time period than would be predicted by the maternal venous blood ethanol concentration.

Acetaldehyde↗
PubMed1983

Specificity of hepatic aldehyde dehydrogenase inhibition by calcium carbimide (calcium cyanamide) in the rat.

Acute, oral administration of 7.0 mg/kg calcium carbimide (calcium cyanamide) to rats, 2 h before sacrifice, produced complete inhibition of hepatic, low-Km (less than 1 microM acetaldehyde) mitochondrial and cytosolic aldehyde dehydrogenase enzymes and significantly inhibited high-Km (approximately 1 mM acetaldehyde) mitochondrial, cytosolic, and microsomal aldehyde dehydrogenase isozymes. Calcium carbimide had no effect on several other hepatic enzyme activities including mitochondrial glutamate dehydrogenase and monoamine oxidase, cytosolic alcohol dehydrogenase, microsomal NADPH-cytochrome c reductase, benzo[a]pyrene hydroxylase and aminopyrine N-demethylase activities, and microsomal cytochrome P-450 content. It is concluded that calcium carbimide is a more specific inhibitor of hepatic aldehyde dehydrogenase enzymes than disulfiram.

Aldehyde Dehydrogenase↗
PubMed1983

Gas-liquid chromatographic determination of salsolinol in the striatum of rat brain during the calcium carbimide--ethanol interaction.

An assay has been developed for the measurement of salsolinol in brain tissue that involves tissue homogenization in dilute hydrochloric acid, purification of the supernatant by cation-exchange chromatography, derivatization of the eluate with heptafluorobutyric anhydride, and analysis by gas-liquid chromatography with electron capture detection using p-tyramine as the internal standard. The lower limit of quantitative sensitivity, using aqueous standards, is 2.5 ng salsolinol per brain sample. This assay was used to study salsolinol formation in rat brain during the calcium carbimide-ethanol interaction. Rats were administered ethanol (1.0 g/kg) by oral intubation 3 h after intraperitoneal administration of calcium carbimide (7.0 mg/kg). Salsolinol was measured in the striatum over a 270-min period after ethanol administration. Salsolinol concentration appeared to be maximal (275 ng/g) at 90 min and then declined with an apparent elimination half-life of 39.8 min.

Animals↗
PubMed1983

Inhibition of hepatic aldehyde dehydrogenases in the rat by calcium carbimide (calcium cyanamide).

Oral administration of 7.0 mg/kg calcium carbimide (calcium cyanamide, CC) to the rat produced differential inhibition of hepatic aldehyde dehydrogenase (ALDH) isozymes, as indicated by the time-course profiles of enzyme activity. The low-Km mitochondrial ALDH was most susceptible to inhibition following CC administration, with complete inhibition occurring at 0.5 h and return to control activity at 96 h. The low-Km cytosolic and high-Km mitochondrial, cytosolic, and microsomal ALDH isozymes were inhibited to a lesser degree and (or) for a shorter duration compared with the mitochondrial low-Km enzyme. The time course of carbimide, the hydrolytic product of CC, was determined in plasma following oral administration of 7.0 mg/kg CC to the rat. The maximum plasma carbimide concentration (102 ng/mL) occurred at 1 h and the apparent elimination half-life in plasma was 1.5 h. Carbimide was not measurable in the liver during the 6.5 h time interval when carbimide was present in the plasma. There were negative, linear correlations between plasma carbimide concentration and hepatic low-Km mitochondrial, low-Km cytosolic, and high-Km microsomal ALDH activities. In vitro studies demonstrated that carbimide, at concentrations obtained in plasma following oral CC administration, produced only 19% inhibition of low-Km mitochondrial ALDH and no inhibition of low-Km cytosolic and high-Km microsomal ALDH isozymes. These data demonstrate that carbimide, itself, is not primarily responsible for hepatic ALDH inhibition in vivo following oral CC administration. It would appear that carbimide must undergo metabolic conversion in vivo to inhibit hepatic ALDH enzymes, which is supported by the observation of no measurable carbimide in the liver when ALDH was maximally inhibited following oral CC administration.

Aldehyde Dehydrogenase↗
PubMed1981

Determination of carbimide in plasma by gas-liquid chromatography.

A sensitive and selective method for the measurement of carbimide, the hydrolytic product of calcium carbimide, in plasma is described. The procedure involves extraction with ethyl acetate, derivatization with heptafluorobutyric anhydride and analysis by gas-liquid chromatography with electron-capture detection. The lower limit of sensitivity of the assay is 5.0 ng/ml carbimide in plasma. The overall accuracy of the procedure is 96.1% with a coefficient of variation not exceeding 8.7%. This assay has been used to investigate the time-course of plasma carbimide concentration in the rat following oral administration of calcium carbimide.

Chromatography, Gas↗
PubMed1981

A comparative review of the pharmacological and toxicological properties of disulfiram and calcium carbimide.

Disulfiram and calcium carbimide are widely used alcohol deterrents. Their safe use, however, requires a knowledge of their pharmacology, toxicity, and interactions with alcohol and other drugs. The absorption, metabolism, and elimination of these compounds are described, and elimination of these compounds are described, as is the mechanism of their reaction with ethanol. The effects and limitations of the interaction between ethanol and disulfiram and calcium carbimide are discussed. Four areas of concern regarding toxicity are discussed, including medical complications of the reactions with alcohol, toxicity associated with repeated doses of disulfiram or calcium carbimide, possible interactions with other drugs, and acetaldehyde-induce hepatotoxicity and cardiotoxicity.

Acetaldehyde↗
PubMed1980

Intraindividual variability in the calcium carbimide-ethanol interaction.

Four male alcoholic volunteers ingested two doses of 0.4 g/kg ethanol at 10h and 13.25 h after oral administration of 0.7 mg/kg calcium carbimide (CC). The interaction consisted of increases in blood acetaldehyde concentration and heart rate. For all the subjects, the magnitude of increased blood acetaldehyde concentration was less for the second ethanol dose, and for three individuals, the heart rate increase was less for the second ethanol dose. In the second study, one subject ingested 0.4 g/kg ethanol at 12h after oral administration of 0.7 mg/kg CC in three, separate, experimental sessions. For the interaction, there was large intraindividual variability in the increased blood acetaldehyde concentration, and small variability in the increased heart rate. There were significant, positive linear correlations between blood acetaldehyde concentration and heart rate for two of the three experiments, and there was appreciable variability in the slopes of the regression lines. The results indicate that under the conditions of these studies, the intensity of the CC-ethanol interaction experienced by an individual could be reduced for the ingestion of a second dose of ethanol during the same drinking session. Furthermore, there could be appreciable intraindividual variability in the intensity of the interaction from one drinking session to the next.

Acetaldehyde↗
PubMed1980

Calcium carbimide--ethanol interaction.

Each of 4 male alcoholic subjects received 0.7 mg/kg calcium carbimide (CC) orally 12 hr before ingestion of 0.25 gm/kg ethanol on 3 separate occasions. The CC-ethanol interaction consisted of increased blood acetaldehyde level and elevated heart rate. For each individual there was small variability in the area under the curve (AUC) values of the blood ethanol level--time course profiles for the 3 experiments, indicating a consistent extent of ethanol absorption. For subjects 1, 2, and 3 there was appreciable intraindividual variability in the AUC and the peak blood acetaldehyde levels of the blood acetaldehyde level--time course curves; the variation in these parameters was small for subjects 4. The intraindividual variability in the peak heart rate response was small for subjects 1 and 2 and appreciable for subjects 3 and 4. Regression analysis of the blood acetaldehyde level--heart rate data for each of the 3 experiments conducted on the 4 subjects revealed that there were positive, linear correlations. There was appreciable intraindividual variability in the slope values for the 3 experiments. The results of this study, conducted on 4 male alcoholics, suggest that for other alcoholic subjects there could be appreciable intraindividual variability in the intensity of the CC-ethanol interaction.

Acetaldehyde↗