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PubMed1992

Hypoventilation after acute phrenicotomy of the urethane anaesthetized rats.

The aim of this study was to explore the mechanism resulting in hypoventilation in rats with denervated diaphragm. Bilateral cervical phrenicotomy (PX) was performed in 15 male rats anaesthetized with urethane (1.3 g/kg i.p.); other 8 rats were sham operated (SX). Ventilation, PaCO2 and the integrated EMG of the external intercostal muscles (iEMG) were measured before and after the surgery, at regular intervals, up to 4 hours postoperatively. During the 4 hours after PX there was a progressive decrease in minute ventilation and an increase in PaCO2 compared with the control values and with that in the SX rats. The increase in PaCO2 was accompanied by an increase in the peak amplitude of the iEMG to 155 +/- 18% of control values after PX and to 228 +/- 33% 4 hours later. Despite the augmented EMG activity tidal volume gradually decreased. The iEMG of the intercostal muscles, however, did not reach a maximum because the shortlasting stimulation of breathing by acute hypercapnia and hypoxia as the result of added dead space (0.5 ml) increased the iEMG still further. These results indicate that both the central and peripheral mechanisms contribute to hypoventilation in anaesthetized rats with denervated diaphragm.

Anesthesia↗
PubMedDate not supplied

Biphasic effects of atropine on sensory-evoked hippocampal rhythmical slow activity in urethane-anaesthetized rats.

This study investigated the response of hippocampal RSA, recorded from electrodes in CA1 and the contralateral dentate gyrus of urethane-anaesthetized rats, to atropine sulphate administered at 15 min intervals in a cumulative dose-response schedule (1, 3, 10, 50 and 50 mg x kg(-1) i.p.). The power of CA1 and dentate gyrus RSA in the 3-7 Hz band was increased after administering the first 3 doses of atropine (1, 3 and 10 mg x kg(-1) cumulatively) in rats held in the stereotaxic frame or removed from the frame and given electrical sensory stimulation to the base of the tail. This increase in RSA was dependent on sensory input, since it was not seen in animals outside the frame unless sensory stimulation was given, and it was abolished by increasing the dose of atropine (an additional 50 and 50 mg x kg(-1) cumulatively). Methylatropine (6 mg x kg(-1) i.p.) did not increase RSA power. The biphasic effect of atropine on sensory-evoked hippocampal RSA activity may be explained by differential effects at pre- and post-synaptic sites e.g. in the septo-hippocampal system or on pathways processing sensory information.

Animals↗
PubMed1991

[Dynamics of proliferative activity of cultures of organotypic epithelial-mesenchymal recombinants from embryonic lungs of intact and urethane-receiving mice].

The dynamics of proliferative activity of cells was studied in the cultures of organotypic recombinants obtained from embryonic lung epithelium (E) and mesenchyma (M) of the intact and treated transplacentally by urethane mice (strain A). The labelling index (LI) of E and M in the aggregates obtained from treated embryonic lungs (EtMt) was significantly higher than LI in the aggregates from intact embryonic lungs (EiMi) in all days of cultivation (4-7-14). M from the treated embryonic lungs stimulated LI of the intact E (EiMt) but M from the intact embryonic lungs decreased LI of the treated E (EtMi).

Animals↗
PubMed1990

Dual effects of cholecystokinin-octapeptide on duodenal motility of urethane-anesthetized rats.

Intravenous administration of cholecystokinin octapeptide (CCK-8) to urethane-anesthetized rats produced both inhibitory and excitatory effects on intestinal motility. The inhibitory effect, evident as a transient relaxation or inhibition of distension-induced reflex contractions, was abolished by adrenoreceptor blockade, guanethidine pretreatment or removal of the celiac ganglion complex, but was hexamethonium-and atropine-insensitive. The excitatory action of CCK-8 was atropine- and hexamethonium-sensitive, while being unaffected by guanethidine pretreatment. Ligation experiments indicated that the excitatory effect of CCK-8 originates from a stimulant action on structures in the upper duodenum/pyloric sphincter from which a propagated contraction travels to the distal duodenum. We conclude that i.v. CCK-8 inhibits small intestinal motility by directly activating sympathetic neurons in the celiac ganglion and initiates a propagated form of intestinal motility by stimulating neural elements in the upper part of the small intestine.

Animals↗
PubMed1978

Cardiac output and peripheral resistance of swim-trained rats under urethan anesthesia.

Several circulatory variables were determined in control and swim-trained white rats under urethan anesthesia. Trained animals exhibited significantly lower heart rate and cardiac index and significantly higher peripheral resistance than control animals. Blood pressure, systolic index and left ventricular work output were not statistically different in the two groups. These results suggest an alteration of resting cardiovascular regulation in trained animals. Beta adrenergic mechanisms are suppressed by increased parasympathetic tone, and the resting circulatory balance is maintained mainly by increased alfa adrenergic mechanisms.

Anesthesia, General↗
PubMed1990

Intraluminal release of PGE2 due to gastric perfusion of urethane-anaesthetized rats with hydrochloric or taurocholic acid.

We have measured the intragastric release of prostaglandin E2-like immunoreactivity (PGE2-li), pH changes and mucosal damage in response to gastric perfusion with hydrochloric or taurocholic acid at pH 1.5 in urethane-anaesthetized rats. Hydrochloric acid-perfusion caused a reversible decrease in pH values, no damage to the gastric mucosa and an intraluminal release of PGE2-li. Exposure to an ulcerogenic dose (25 mM) of taurocholic acid produced an intraluminal release of PGE2-li much higher than that of the non-ulcerogenic perfusion with hydrochloric acid. These findings indicate that intraluminal release of PGE2-li, thought to play a role as an endogenous antiulcer factor, can occur in response to a stimulus producing a significant damage of the gastric mucosa or to a mild irritant stimulus.

Anesthesia↗
PubMed1988

Convulsant-induced changes in perforant path-dentate gyrus excitability in urethane anesthetized rats.

The dentate gyrus of intact urethane-anesthetized rats was employed to evaluate the effects of different convulsive agents on granule cell excitability. One purpose of this study was to determine whether mechanisms of action suggested from in vitro studies of these compounds could be demonstrated over clinically relevant dose ranges in vivo. The data demonstrate that drugs capable of antagonizing gamma amino butyric acid (GABA)-mediated inhibition produced similar effects on the intact hippocampus. Bicuculline, picrotoxin, pentylenetetrazol and the insecticide lindane increased granule cell excitability to perforant path stimulation. The primary cause of this was an increase in the innate excitability of the granule cells. These compounds also modified field potentials in a manner consistent with a reduction in early GABA-mediated inhibition. They did not affect synaptically mediated facilitation. The magnitudes of the effects were dose dependent, and changes were clearly measurable at exposures that produce clinical effects in nonanesthetized rats. Other convulsants could be readily differentiated from those affecting GABA-mediated inhibition. Kainic acid depressed granule cell responses to perforant path stimulation and severely depressed both inhibition and facilitation. A decrease in granule cell responsiveness was also produced by exposure to beta carboline. Exposure to strychnine had little effect on granule cell excitability. These data indicate that for bicuculline, picrotoxin, pentylenetetrazol and lindane, an apparently selective antagonism of GABA-mediated inhibition is clearly demonstrable at exposures that also produce clinical intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Changes in cyclic adenosine 3':5'-monophosphate-dependent protein kinases during the progression of urethan-induced mouse lung tumors.

The cyclic adenosine 3':5'-monophosphate (cAMP)-dependent protein kinases in lung adenomas are functionally different from those of normal lung. The relevance of this change to neoplastic conversion was examined by comparing tumor kinases with those obtained from the normal cell of origin and by studying the kinases at different stages of tumor growth. Lung tumors were collected from A strain mice at different times after a single injection of urethan. These tumors are predominantly of alveolar type two cell origin, and cAMP-binding proteins in extracts from isolated type two cells and from lung adenomas at various stages of tumor progression were compared. Both the incorporation of the cAMP photoaffinity analogue, cyclic 8-azidoadenosine 3':5'-[32P]monophosphate (8-N3-[32P]cAMP), into the regulatory subunits of the type I (RI) and type II (RII) cAMP-dependent protein kinases and the autophosphorylation of RII were similar in extracts from whole normal lung and from type two cells. Altered protein kinases are thus not characteristic of normal type two cells. Lung tumors showed a decrease in photodetectable RII which correlated in degree with tumor size and extent of anaplasticity. This decreased RII photolabeling during tumor growth was associated with increased RII autophosphorylation. In contrast, decreased RII photolabeling in extracts from neonatal lung is accompanied by a substantial decrease in RII autophosphorylation. The characteristics of RII during normal development thus clearly differ from those during neoplastic development. An increase in the amount of an Mr 37,000 proteolytic fragment derived from R-subunits was also noted as a function of tumor progression. DEAE-cellulose chromatography of tumor cytosol showed that the increase in the amount of Mr 37,000 protein was accompanied by increased subunit dissociation of the type I isozyme. The dissociated RI subunit has been shown to be more sensitive to cleavage by a Ca2+-dependent neutral protease than when RI was in the holoenzyme form. This protease is present in both normal lung and lung adenomas, and its activity increases during the later stages of tumor progression. A comparison of cAMP binding and the light-induced covalent incorporation of 8-N3-[32P]cAMP showed that, for both RI and RII, photoincorporation was about 75% as efficient as noncovalent binding. In contrast, although the Mr 37,000 fragment can be photolabeled with low concentrations of 8-N3-[32P]cAMP, noncovalent cAMP binding to the endogenous Mr 37,000 fragment could not be demonstrated with a standard filtration assay. Such altered cAMP binding characteristics following Ca2+-dependent proteolysis of R-subunits would all

Affinity Labels↗
PubMed1985

Dual effects of clonidine on micturition reflex in urethane anesthetized rats.

The effects of clonidine (CLO) on reflexly activated bladder motility have been examined in urethane-anesthetized rats and compared to its effects on field stimulation-induced contractions of isolated urinary bladder. Intravenous CLO suppressed micturition reflex transiently in a yohimbine-sensitive manner. The suppressive effect of i.v. CLO was greater after surgical sympathectomy (bilateral section of the hypogastric nerves). Intracisternal CLO was more effective than topical (on the bladder dome) or intracerebroventricular CLO in suppressing micturition. When tested in experimental conditions involving activation of both excitatory and inhibitory reflexes to the bladder CLO produced either inhibitory and/or excitatory effects on bladder motility in dependence of factors such as dose, route of administration and integrity of the sympathetic (inhibitory) innervation to the bladder. CLO suppressed bladder contractions produced by dimethylphenilpiperazinium, a ganglionic stimulant, and reduced those produced by postganglionic nerve stimulation. CLO inhibited, in a yohimbine-sensitive manner, amplitude of field stimulation-induced contractions of isolated rat bladder, and its effectiveness was inversely related to the frequency of stimulation. Our findings are suggestive that the inhibitory action of CLO on micturition reflex is counteracted, in normal animals, by a negative feedback on sympathetic inhibitory influences carried out through the hypogastric nerves.

Anesthesia↗
PubMed1987

H-2-controlled genetic susceptibility to pulmonary adenomas induced by urethane and 4-nitroquinoline 1-oxide in A/Wy congenic strains.

The genetic effect of the H-2 complex on the development of chemically induced pulmonary adenomas was clearly demonstrated in H-2 congenic strains with an A/Wy background which had a high susceptibility to pulmonary adenoma. A single subcutaneous injection of either urethane or 4-nitroquinoline 1-oxide was given to nine strains of mice. Among them, the number of adenoma foci per mouse was significantly higher in A/Wy (haplotype H-2a), A/J (H-2a), A.TL (H-2tl) and A.AL (H-2al) than in A.BY (H-2b), A.SW (H-2s), A.CA (H-2f) and A.TH (H-2t2) strains. In addition, the average number of adenoma foci in A/Wy (H-2a) was more than 20 times that in the B10.A (H-2a) strain. Thus, multiplicity of adenoma foci appeared to be regulated by at least two genes, one of which is located in the I or S region in the H-2 complex and the other in the non-H-2 genetic background. The genes in the H-2 complex were distinct from Pas-1 locus, which is probably identical to ptr.

4-Nitroquinoline-1-oxide↗
PubMed1988

[Effect of glucuronic acid on the carcinogenic action of urethane, dibutylnitrosamine and 7,12-dimethyl[A]anthracene].

C57W and SHR mice were given intraperitoneal injections of 100 or 300 mg/kg body weight glucuronic acid (in isotonic NaCl solution) 15-30 minutes prior to treatment with urethan, dibutylnitrosamine or 7,12-dimethyl-1,2-benzanthracene. This resulted in a lower carcinogenic effect on the lung and the incidence of lung adenoma was half that registered in the animals who had received a carcinogen only.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Central action of prostaglandin E2 and its methyl ester in the induction of hyperthermia after their systemic administration in urethane-anesthetized rats.

Intravenous injection of prostaglandin (PG) E2 (0.01-1.0 mg/kg) induced a dose-dependent increase in the rectal temperature of urethane-anesthetized rats; the maximum change attained was 0.14 +/- 0.08 to 1.38 +/- 0.16 degrees C at 23 to 51 min after injection. The i.v. injection of PGE2 methyl ester (PGE2-Me), a lipophilic derivative of PGE2, resulted in hyperthermia 1.5-fold higher than that by PGE2 injection over the same dose range. The hyperthermia was associated with tachycardia, hypertension, cutaneous vasodilation and a rise in abdominal skin temperature. Using [3H]PGE2 and radioimmunoassay, we showed PGE2 to be transported into the brain immediately (15 sec) after the i.v. injection of the PG; the PGE2 content ranged from 2.3 +/- 0.5 to 102.6 +/- 5.5 ng/g of brain when given at 0.01 to 1.0 mg/kg, which was 0.07 to 0.13% of the administered dose. When [3H]PGE2-Me was used, the radioactivity in the brain at 15 sec after injection was 1.3- to 2.9-fold higher than that after [3H]PGE2 injection. However, 80% or more of PGE2-Me was hydrolyzed rapidly and recovered as PGE2 in the brain within 15 sec post-injection. PGE2-Me disappeared within 5 min. When PGE2 or PGE2-Me administered i.v. was followed in terms of PGE2, it decreased gradually in the brain with a half-life of 9.0 to 9.5 min in both cases, and was almost undetectable (less than 0.7 ng/g of brain) at the time when rectal temperature reached a peak. The maximum change and duration of hyperthermia were correlated closely with the PGE2 content in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Temporary liver support using a new type of sorbent. A urethane sheet embedded with powdered charcoal.

A new sorbent, urethane sheet embedded with powdered charcoal (UPC, BESPORE), which had been developed for use in a temporary liver support system, has been clinically applied since 1984. This system consists of a UPC plasma-perfusion circuit (using a recirculation system) followed by a supplementary 0.8 L plasma exchange, using hemodialysis for the purpose of performing both removal and supplementary therapy at the same time. On average, approximately 40% of both bilirubin and bile acid are removed, with the osmolality gap reduced by 30%. This system is effective for prolongation of life in patients with chronic hepatic failure and those with acute hepatic failure that has become chronic. It can be considered an effective maintenance therapy for patients before liver transplantation.

Adsorption↗
PubMed1988

[Oxygen consumption and RQ-values in rats anesthesized with urethane and pentobarbital during continuous infusion of noradrenaline with and without glucose load].

For demonstration of the calorigenic effects of catecholamines on narcotized rats, ethylurethane and pentobarbital proved to be equally suitable as narcotics. Under urethane, narcotized rats showed no disorders of either glucose resorption or glucose utilization. With excessive oral supply, glucose becomes the preferential substrate in the energy metabolism of these animals.

Animals↗
PubMed1988

Cardiovascular and ventilator effects of vadocaine hydrochloride in urethane-anaesthetized rats and guinea-pigs.

Urethane-anaesthetized rats and guinea-pigs were used to compare the cardiovascular, electrocardiac and ventilator effects of Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine), lidocaine hydrochloride and codeine phosphate. In rats, vadocaine and lidocaine, only at the largest dose tested (64 mumol/kg i.v.), reduced mean arterial pressure (MAP), heart rate (HR) and ventilation rate (VR). Codeine reduced VR dose-dependently, MAP decreased only at the largest dose of 64 mumol/kg, and HR was not affected at the doses tested. In guinea-pigs, neither vadocaine nor lidocaine had any clear effects on MAP. HR was significantly reduced at the doses of 4 and 16 mumol/kg of vadocaine and 16 and 64 mumol/kg of lidocaine. Vadocaine and lidocaine 16 mumol/kg i.v. caused a significant reduction in VR. Lidocaine 64 mumol/kg did not further reduce VR. The electrocardiac effects included prolongation of P-Q interval both in the vadocaine and lidocaine group. Prolongation of Q-Tc, deepening of Q and S, decrease in R amplitude, and inversion of T waves were seen only in the vadocaine group. To induce changes in the P-Q interval, four times less vadocaine than lidocaine was needed. The acute toxic dose of vadocaine in rats ranged from 64 to 100 mumol/kg i.v.; lidocaine and codeine caused no lethalities in rats at the dose range 1-64 mumol/kg i.v. In guinea-pigs, the lethal dose of 64 mumol/kg i.v. produced AV blocks followed by asystole or ventricular fibrillation. At the dose of 64 mumol/kg i.v. of lidocaine 3 guinea-pigs out of 11 died.

Anesthesia↗
PubMed1986

Immune function in adult C57BL/6J mice following exposure to urethan pre- or postnatally.

Administration of urethan (URE or ethyl carbamate) to mice results in the development of a variety of tumors, and, in certain strains of mice, marked suppression of the immune response. Perinatal exposure of mice to URE has been found to result in increased tumor induction compared to exposure of adult animals. In the present study, the effects of perinatal exposure to URE on the development of immunocompetence was investigated. Pregnant mice were injected with total doses of either 0.5 or 1.0 mg URE/g of body weight over days 7-16 of gestation or pups of nontreated dams were administered a total dose of 2.0 mg URE/g of body weight over postpartum days 5-14. Postnatal exposure to URE suppressed NK (natural killer) cell activity but left intact other measured parameters of the host defense system. Prenatal exposure, on the other hand, resulted in elevated leukocyte counts and a trend toward increased spleen and thymus size in offspring of treated mothers. Humoral immune function, as measured by the IgM response to sheep erythrocytes, was suppressed in pups from dams injected with a total of 1.0 mg/g URE. These results indicate that marked differences in immunopharmacologic effects may be observed if chemical exposure occurs at different times during the ontogeny of the immune system.

Animals↗
PubMed1986

[Analysis of the DNA content of urethane-induced liver tumors in mice].

Administration of urethan (three times per 1 mg calculated per 1 g of the animal mass) after partial hepatectomy resulted in the development of liver tumours classified as adenomas in 62.8 per cent of mice 12 months after treatment. In the cells isolated from 85 adenomas and from the surrounding liver, DNA-fuchsin content was determined cytophotometrically. Three types of DNA distribution were distinguished, with the mode in the region of near-diploid (26%), near-tetraploid (71.8%), or near-octaploid (2.2%) DNA value. Most commonly DNA distributions were polymodal, but unimodal ones also occurred. The number of binucleated cells in tumours was significantly decreased. In the liver of one of the same animal, morphologically similar tumours of all the three types of DNA distribution could be found. The increase in the hepatocyte ploidy level in the initial parenchyma by preliminary repeated treatments with CCl4, had no effect either on the occurrence of tumours, or on their ploidy level. No correlation was found between the DNA content, the size and histological structure of tumours.

Animals↗
PubMed1985

N-substituted urethanes as potential antiinflammatory agents.

Sixteen N-substituted urethanes were investigated as potential antiinflammatory agents. Most of them showed no stronger activity than phenylbutazone. The most active in the xylene hyperemia test were N,N'-dicarbethoxy-N,N'-dicyclohexyl-1,3-diaminopropane (XVI) and cyclohexyl piperidine-1-carboxylate (XIII). None of the studied compounds showed analgesic activity.

Animals↗