bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of suxamethonium on cardiovascular and respiratory function in the anaesthetized horse
Authors: LEES P. , TAVERNOR W. D. 
Published: July 2012

In horses anaesthetized with halothane the intravenous administration of suxamethonium chloride, at a dose level of 0.2 mg/kg, produced a short‐lived period of hypoventilation, which was associated with increases in arterial blood Pco2 levels and in plasma concentrations of bicarbonate, sodium and potassium ions, and reductions in arterial blood pH and Po2 values.
The respiratory depressant action of suxamethonium chloride 0.2 mg/kg was accompanied by increases in blood pressure and heart rate. Doses of suxamethonium chloride 0.4 mg/kg produced similar but quantitatively greater changes in cardiovascular and respiratory function. These effects were not accompanied by cardiac arrhythmias, with the exception of one animal, in which an unusually prolonged period of apnoea occurred.
The cardiovascular effects of suxamethonium during halothane anaesthesia were diminished but not abolished when the respiratory depressant action of suxamethonium was prevented by applying positive pressure ventilation.
The cardiovascular effects of suxamethonium in horses anaesthetized with halothane were partially antagonized by propranolol and completely antagonized by hexamethonium. It is suggested that the cardiovascular effects of suxamethonium are mediated by two distinct mechanisms: reflexly mediated increases in heart rate and sympathetic vasoconstrictor tone due to the respiratory depression, and a direct stimulant action of suxamethonium on peripheral, autonomic ganglia.
Much less pronounced changes in cardiovascular function, but not in respiratory function, were recorded when suxamethonium was administered to horses anaesthetized with ether.
A slight degree of tachyphylaxis to the cardiovascular and respiratory effects of suxamethonium was recorded in horses anaesthetized with halothane.
Some atypical effects of suxamethonium on respiration are described.
Inhibition of the carotid sinus reflex by the chronic administration of propranolol
Authors: DUNLOP D. , SHANKS R. G. 
Published: July 2012

The changes in heart rate and arterial pressure produced by the intravenous injection of isoprenaline (0.5 μg/kg), noradrenaline (1.0 μg/kg), phenylethylamine (0.5 mg/kg), amphetamine (0.5 mg/kg) and by bilateral occlusion of the carotid arteries and by stimulation of the central ends of both vagus nerves have been recorded in groups of dogs anaesthetized with pentobarbitone.
The acute intravenous injection of propranolol (1 mg/kg) reduced the increases in heart rate produced by the six procedures, the increases in arterial pressure in response to the last five procedures and the decrease in pressure produced by isoprenaline.
This decrease produced by propranolol in the pressor responses resulted from a reduction in the increases in cardiac output elicited by the five procedures and has been attributed to blockade of cardiac adrenergic β‐receptors.
Three groups of dogs were pretreated for 6 weeks by the oral administration of either placebo, propranolol 50 mg/kg daily or propranolol 10 mg/kg twice daily. The responses to the six test procedures were obtained 17–24 hr after the last dose of propranolol, when only minimal blockade of adrenergic β‐receptors was present. In the propranolol‐treated groups, the pressor response to carotid occlusion but not to the other test procedures was significantly reduced.
The pressor response to carotid occlusion was not reduced in a fourth group of dogs given a single dose of propranolol (50 mg/kg) 24 hr before the test procedures.
The mechanism of this selective reduction in the pressor response to occlusion of the carotid arteries is not clear. It is suggested that it may contribute to the hypotensive action of propranolol in man during prolonged oral administration.
The role of Uptake2 in the extraneuronal metabolism of catecholamines in the isolated rat heart
Authors: LIGHTMAN S. L. , IVERSEN L. L. 
Published: July 2012

. (±)‐3H‐NA and labelled metabolites of NA were estimated in rat hearts after perfusion with various concentrations of NA in the range 0·01–50·0 μg/ml. Labelled metabolites of NA accounted for only a small proportion of the total uptake of radioactivity at low perfusion concentrations, but accounted for 50% of the total uptake at 1 μg NA/ml., thereafter declining to progressively smaller proportions at higher perfusion concentrations.
. If the formation of labelled metabolites of 3H‐NA was blocked by a combination of monoamine oxidase and catechol‐O‐methyl transferase inhibitors, the accumulation of unchanged 3H‐NA was doubled when hearts were perfused with 1 μg NA/ml.
. In hearts perfused with 0·5 μg NA/ml., an accumulation of unchanged 3H‐NA was demonstrated in the presence of a combination of metabolic inhibitors and metaraminol. This appeared to be due to Uptake2, since the accumulation of NA under these conditions could be prevented by a low concentration of normetanephrine.
. Phenoxybenzamine prevented extraneuronal uptake (Uptake2) and metabolism of 3H‐NA with an estimated ID50 of 2·5 μm. The inhibition of Uptake2 by phenoxybenzamine (2·0 μm) was diminished at very high NA concentrations, suggesting that the drug may act competitively with NA.
. It was concluded that Uptake2 operates at all catecholamine concentrations in the rat heart, but that in the lower range (less than 2·5 μg/ml. for NA and less than 0·75 μg/ml. for adrenaline) any catecholamine taken up by this process is rapidly metabolized. Thus the accumulation of unchanged amine is seen only at high perfusion concentrations.
. The relevance of these results to an understanding of the possible physiological and pharmacological importance of Uptake2 is discussed.
Carbon tetrachloride metabolism in the rabbit
Authors: FOWLER J. S. L. 
Published: July 2012

. Carbon tetrachloride was administered by stomach tube to rabbits and its distribution in fat, liver, kidney and muscle studied by gas liquid chromatography, during the next 48 hr.
. Chloroform, hexachloroethane and two unidentified chlorinated metabolites were detected in the tissues.
. Hexachloroethane may arise by dimerization of free trichloromethyl radicals.
Cephalexin: human studies of absorption and excretion of a new cephalosporin antibiotic
Authors: GOWER P. E. , DASH C. H. 
Published: July 2012

. Serum levels, half‐lives and urine concentrations of cephalexin, an oral cephalosporin antibiotic which is unique in its absorption and excretion, are reported in human volunteers, fasting, non‐fasting and non‐fasting plus probenecid. Accumulation does not seem to occur.
. Cephalexin clearance was 376 ml./min and the ratio of cephalexin/creatinine clearances was 2·6 in one volunteer.
. Cephalexin had no effect on the urinary excretion of leucocytes, red cells or protein.
. The very high rate of absorption giving high serum levels and urine concentrations suggest cephalexin will be a useful antibiotic in susceptible bacterial infections in man.
The relevance of β‐receptor blockade to ouabain‐induced cardiac arrhythmias
Authors: DOHADWALLA A. N. , FREEDBERG A. S. , WILLIAMS E. M. VAUGHAN 
Published: July 2012

. (+)‐propranolol and (±)‐propranolol are comparable in their potency as a local anaesthetic on the intact and desheathed frog sciatic nerve.. (±)‐propranolol is much more potent than (+)‐propranolol as a β‐receptor blocking agent and also more effective than the latter in protecting guinea‐pigs against ouabain‐induced ventricular fibrillation.. In isolated rabbit atria (–)‐, (+)‐ and (±)‐propranolol, and I.C.I. 50172, which has hardly any local anaesthetic activity, greatly reduce the rate of rise of the intracellularly recorded action potential at concentrations which have no significant effect on electrical threshold, contractions, spontaneous frequency, maximum driving frequency, repolarization time or conduction velocity.
The distribution of 3H‐labelled cardenolides between isolated guinea‐pig atrial tissue and circulating, oxygenated whole blood
Authors: LÜLLMANN H. , PETERS T. , van ZWIETEN P. A. 
Published: July 2012

. An experimental method was developed that allowed the incubation of isolated organs in circulating whole blood. The circulating blood was oxygenated with a specially designed dise‐oxygenator and drawn through the system by means of a roller pump.
. The method proved suitable for guinea‐pig isolated atria, rabbit duodenum and to a lesser extent for chronically denervated rat diaphragm. Isolated atria could be kept for several hours. Various parameters of the circulating blood (haemolysis, pH, O2 saturation, concentration of electrolytes) remained satisfactory for at least 5 hr. The method proved convenient for pharmacological and kinetic studies on isolated organs, suspended in whole blood of the corresponding species. The organs showed normal spontaneous mechanical activity and also responded to electrical stimuli and various drugs.
. The uptake of 3H‐labelled ouabain, digoxin, digitoxin and digitoxigenin was studied in guinea‐pig isolated atria, suspended in circulating blood. The uptake reached equilibrium after 60–90 min. With respect to the total serum radioactivity the “apparent” tissue/medium (T/M) ratios obtained for the four drugs were within the range 0.4–1.1. If, however, the amount of free, non protein bound drug was taken as a base for the calculations, the following “true” T/M ratios were obtained: 3H‐ouabain 0.45; 3H‐digoxin 1.6; digitoxin 8.8; digitoxigenin 8.4. These values are virtually the same as those obtained with atria, suspended in an aqueous medium. Obviously, the uptake of 3H‐cardenolides from whole blood is determined by the amount of free non‐proteinbound drug.
. 3H‐digitoxin and 3H‐digitoxigenin were taken up by guinea‐pig erythrocytes to a small extent. No measurable amounts of 3H‐ouabain and 3H‐digoxin were taken up by erythrocytes.
Muscarinic component of splanchnic‐adrenal transmission in the dog
Authors: KAYAALP S. O. , McISAAC R. J. 
Published: July 2012

. The effect of atropine on catecholamine release evoked by stimulation of the splanchnic nerve was studied in the adrenal medulla of the dog. The magnitude of the catecholamine release was estimated biologically on the basis of the pressor response occurring in the perfused and acutely sympathectomized hindquarters of the same dog by comparing it with responses elicited by intravenous injection of adrenaline.
. Atropine reduced the responses to nerve stimulation, and appeared to have a more prominent effect on the responses elicited by stimulation at moderate frequency (10 pulses/sec).
. Hexamethonium or nicotine caused a more powerful, but not complete, blockade of transmission; the subsequent injection of atropine caused a further inhibition of the residual responses, leading to a complete, or near complete, abolition of the release by nerve stimulation.
. The data were taken as evidence that transmission of impulses through muscarinic receptors occurs in normal conditions in the adrenal medulla of the dog, though this type of transmission is less prominent than that through nicotinic receptors.
Effects of calcium, sodium and potassium ions on contractility of isolated atria and their responses to noradrenaline
Authors: TODA N. 
Published: July 2012

. Rabbit left atrial preparations driven electrically at different rates were used for studies on inotropic effects of cations, drugs and coupled pacing. Sino‐atrial node‐atrial preparations were used for investigating the chronotropic effect of noradrenaline.
. The contractile tension‐driving rate relationship was moved upwards by an elevation of [Ca++]o, coupled pacing and noradrenaline. In preparations exposed to Na+‐poor and K+‐free solutions the contractile strength at low driving rates (6 to 30 c/min) was markedly enhanced, but at high rates (120 to 240 c/min) it was not influenced. The contractile strength was reduced at low [Ca++]o and at high [K+]o.
. The positive inotropic effect of noradrenaline was markedly inhibited by a reduction of [Ca++]o and to some extent by a reduction of [K+]o. The noradrenaline‐inotropy was not appreciably affected by an elevation of [Ca++]o and a reduction of [Na+]o.
. Cardiac excitability studied in preparations driven at high rates was enhanced by noradrenaline, a reduction of [K+]o and an elevation of [Ca++]o, but was reduced at low [Ca++]o, low [Na+]o and high [K+]o.
. The positive chronotropic response to noradrenaline was enhanced at high [Ca++]o, low [Na+]o and low [K+]o, but was reduced in solutions deficient in Ca++ or rich in K+.
. Inotropic effects of the ions and of coupled pacing were compared with those of ouabain. It is suggested that characteristic changes in the tension‐rate curve seen in Na+‐poor, K+‐free and ouabain‐containing solutions are correlated with an inhibition of active processes in the cardiac cell membrane, which affect ionic movements across it. It seems likely that mechanisms mediating adrenergic responses of the contractile tissue and the S‐A node are associated with [Ca++]o.
Preliminary investigations of a new beta‐adrenoceptive receptor blocking drug, LB46, in man
Authors: HILL R. C. , TURNER P. 
Published: July 2012

. Preliminary studies in man of a new beta‐adrenoceptive receptor blocking drug, dl‐4‐(2‐hydroxy‐3‐isopropylaminopropoxy)‐indole (LB46), are described.
. LB46, 0.5 mg by oral administration, appeared to be of similar potency to propranolol 20 mg in inhibiting isoprenaline‐induced and exercise‐induced tachycardia.
. In comparable beta‐receptor blocking doses LB46 did not show the negative chronotropic property possessed by propranolol.
The actions of ethinyloestradiol on the pituitary‐adrenal system of the rat
Authors: FLACK J. D. 
Published: July 2012

Summary
. Single doses of ethinyloestradiol stimulate the pituitary adrenal axis of the female rat during quiescent conditions.
. After a stimulus which releases endogenous ACTH, there is an inhibition of the release of corticosterone from the adrenal gland, but an increase in the corticosterone stored in the gland.
. Ethinyloestradiol (1·0 mg/kg) injected acutely or daily for 7 days does not affect the corticosterone binding capacity of plasma in female rats, or the clearance rate of an injection of corticosterone.
. Prolonged treatment with ethinyloestradiol and ACTH inhibits the pituitary‐adrenal response to a stress and to an ACTH injection, indicating a block at the adrenal and pituitary level.
. The adrenal gland recovers more rapidly than the pituitary after cessation of the oestrogen treatment.
. The inhibition of the pituitary‐adrenal response to stress after oestrogen is probably caused by inhibition of cholesterol synthesis as suggested by others. Oestrogens can increase corticoid secretion during non‐stress conditions, however, so precursor lack through exhaustion cannot be excluded.
. It is suggested that the inhibition of the stress response after prolonged ACTH treatment is due to a decrease in sensitivity of the adrenal cortex after frequent ACTH stimulation, but the possibility that it is due to a reduction in circulating cholesterol cannot be ruled out.
Pharmacological significance of biogenic amines in the lungs: noradrenaline and dopamine
Authors: AVIADO DOMINGO M. , SADAVONGVIVAD CHIRAVAT 
Published: July 2012

Summary
. The noradrenaline concentration in the lung was less than 0·5 μg/g in eight animal species.
. In the cat, dog, rabbit and goat, tyramine produced a fall in pulmonary resistance, which was reduced by the administration of either reserpine or cocaine. Although an infusion of noradrenaline increased the content of this amine in the lung of the cat, previously depleted by reserpine, the bronchodilator property of tyramine was not restored. The infusion of isoprenaline did not restore the response to tyramine. The role of either catecholamine in mediating the bronchomotor response to tyramine could not be ascertained.
. The concentration of dopamine was as high as 6·4 μg/g in the goat lung and less than 0·5 μg/g in the lungs of the cat, rabbit, dog, rat, mouse, guinea‐pig and man. Dopamine, injected intravenously into the cat, dog, rabbit and goat, produced a slight rise in pulmonary resistance. This increase was blocked by tolazoline, indicating that the response was mediated by α‐adrenoceptors in the bronchial passages. No procedure has been observed to influence the dopamine content of the lung. The release of dopamine cannot, however, be excluded until the blood in the bronchial veins has been analysed.
Temperature modulation of α‐ and β‐adrenoceptors in the isolated frog heart
Authors: BUCKLEY G. A. , JORDAN C. C. 
Published: July 2012

Summary
. The effects of adrenaline on the isolated frog's heart at 27° C are not antagonized by phentolamine (1·5 × 10−6m) but are abolished at 7° C.
. At 27° C isoprenaline was more potent than noradrenaline, but at 7° C noradrenaline was more potent than isoprenaline.
. Phenoxybenzamine (1·5 × 10−5m) or dibenamine (1·5 × 10−5m) at 7° C abolished the work output induced by adrenaline. When the temperature was raised to 24° C., adrenaline caused an increase in work output.
. It is concluded that in the isolated frog heart there are at least two pools of adrenoceptors, the availability of which can be governed by temperature.
Localization of kininogenase in the rat kidney
Authors: NUSTAD K. 
Published: July 2012

Summary
. The rat kidney kininogenase (KGA) activity was located mainly in the kidney cortex.
. Differential centrifugation of kidney cortex homogenate revealed that the microsomal fraction contained more KGA activity per unit of protein than the other subcellular fractions.
. Subfractionation of the microsomal fraction showed that the KGA activity was recovered in a subfraction also containing high specific activity of both alkaline phosphate and glucose‐6‐phosphatase. It is suggested that the KGA activity is localized in the plasma membrane and/or endoplasmic reticulum membranes of kidney cortical cells.
. Hydrolysis of N‐α‐benzoyl‐l‐arginine ethyl ester at pH 8.5 paralleled the KGA activity.
Influence of halothane and catecholamines on heart rate and rhythm in the horse
Authors: LEES P. , TAVERNOR W. D. 
Published: July 2012

Summary
. Ventricular ectopic beats were recorded in eight of thirteen conscious horses following the intravenous administration of adrenaline in doses of 3 μg/kg. Following pre‐treatment with either atropine sulphate (0.1 mg/kg) or propranolol hydrochloride (0.1 mg/kg), the same dose level of adrenaline failed to produce ventricular ectopic beats.
. Halothane anaesthesia sensitized the equine heart to the arrhythmogenic actions of adrenaline; the incidence and duration of ventricular arrhythmias being greater than in conscious animals. In comparison with the findings in conscious horses, ether anaesthesia appeared to protect the heart against adrenaline‐induced arrhythmias.
. From a comparison of the arrhythmogenic, chronotropic and pressor actions of adrenaline, noradrenaline and isoprenaline during halothane anaesthesia, it was concluded that sensitization to the arrhythmogenic actions of catecholamines resulted primarily from the action of halothane on the ventricle. The results also indicated that the pressor responses to catecholamines during halothane anaesthesia probably played some part in the genesis of arrhythmias.
. No “spontaneous” ventricular arrhythmias were recorded in twenty‐four horses anaesthetized with halothane or in sixteen animals under ether anaesthesia.
. The available evidence indicates that a moderate to fairly severe degree of hypercapnia produced little increase in sympathetic control of the myocardium during halothane anaesthesia; the absence of irregularities in ventricular rhythm during halothane anaesthesia were attributed to this factor.
Noradrenaline content of the heart of the adrenal‐demedullated rat
Authors: BORCHARD F. , VOGT MARTHE 
Published: July 2012

The noradrenaline (NA) concentration in the “heart” (atria and right ventricle) of male rats was estimated at different periods following adrenal demedullation. For 1–3 weeks after the operation there was, in all rats, a reduction in NA content of the tissue, whereas, after somewhat longer intervals, the concentrations had returned to normal in some but not in all animals, so that the range of values was very wide.
In order to be able to test the effect of 2‐aminotetralin on the cardiac NA of animals deprived of their medulla but having normal initial NA concentrations, an interval of 6–8 months was allowed to elapse between operation and injection of the drug; at this time the effect of the drug on cardiac NA was the same in intact and demedullated animals. There is thus no reason to attribute to the adrenal medulla any supporting role in the resynthesis of cardiac NA during periods of increased sympathetic activity.
The time course of the pronounced fall in cardiac NA after adrenal demedullation resembles the time course of sodium retention shown by Gaunt, Renzi, Gisoldi & Howie (1967) to follow this operation. It is therefore suggested that it is the change in electrolyte metabolism which is responsible for the abnormality of NA storage; both phenomena occur in demedullated but not in adrenalectomized animals.
The action of para‐methoxyphenylethylamine (PMPEA) on monosynaptic reflex transmission in the cat
Authors: WALKER R. J. , WILLIS J. C. , WILLIS W. D. 
Published: July 2012

The intravenous injection of para‐methoxyphenylethylamine (PMPEA) into cats produces an increase in the size of the spinal cord monosynaptic reflex. The reflex elevation occurs within 30 s of drug administration, reaches a peak within 2 min, and lasts about 20 min.
The action of PMPEA is similar for extensor (gastrocnemius‐soleus) and flexor (posterior biceps‐semitendinosus) monosynaptic reflexes.
Repeated doses of PMPEA give comparable effects. The degree of monosynaptic reflex elevation is dose related.
The action of PMPEA is antagonized by phenoxybenzamine and by methysergide or cyproheptadine. The combination of phenoxybenzamine with either of the latter is particularly effective in preventing the reflex facilitation by PMPEA.
It is concluded that PMPEA has a central action on the spinal cord. It seems likely that monoaminergic synapses are involved.
Studies on cholinergic transmission in the medial geniculate nucleus
Authors: TEBĒCIS A. K. 
Published: July 2012

Studies were made on the effects of iontophoretically and intravenously administered cholinergic antagonists on the synaptic responses of medial geniculate (MG) neurones evoked by stimulation of the auditory cortex, inferior colliculus and mesencephalic reticular formation.
Atropine specifically blocked a proportion of the excitatory responses evoked by stimulating the auditory cortex, inferior colliculus and reticular formation, although it was without effect on some of them.
Neostigmine and eserine facilitated some excitatory synaptic responses evoked by inferior collicular stimulation.
It is suggested that the feline MG nucleus receives excitatory cholinergic, as well as non‐cholinergic, pathways from the auditory cortex, inferior colliculus and lower brain stem. The cholinergic pathways from the auditory cortex may be either corticofugal fibres or recurrent axon collaterals of afferent projections from the MG nucleus to the cortex. Those from the lower brain stem are possibly the cholinesterase‐containing fibres described by Shute & Lewis (1967).