bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYOCARDIAL FAILURE WITH ALTERED RESPONSE TO ADRENALINE IN ENDOTOXIN SHOCK
Authors: ARCHER L.T. , BLACK M.R. , HINSHAW L.B. 
Published: July 2012

There is a growing concensus that myocardial performance in the early stages of experimental endotoxic and septic shock is relatively normal; however, recent reports have identified an intermediate phase of shock when myocardial dysfunction is clearly apparent.
The mechanism of dysfunction has become a subject of intense investigation. A current view is that altered myocardial responsiveness to circulating catecholamines may play an important role in the dysfunction observed after endotoxin administration. The present studies, in which an isolated working heart preparation of the dog was used, were designed to test this hypothesis. This particular experimental preparation was selected to provide an adequate interpretation of results; cardiac output, afterload, and concentrations of adrenaline reaching the coronary vascular bed were controlled in all experiments. Responses to infusions of adrenaline were recorded in the ‘steady‐state’ condition. Control (non‐shocked) heart responses to adrenaline were highly reproducible in terms of inotropic, chronotropic and coronary vascular behaviour.
Results from the study document myocardial dysfunction within 4–6 h following an LD70 endotoxin administration on the basis of increased left ventricular end diastolic pressure (LVEDP), decreased cardiac power and myocardial efficiency, and depressed negative and positive dP/dt parameters.
Findings suggest significantly altered responsiveness of the myocardium to infused adrenaline at rates of 1, 2, and 5 μg/min with concentrations between 10 and 1 ng/ml blood. LVEDP was elevated while calculated power and efficiency parameters remained significantly below control values during infusion of adrenaline in endotoxin‐treated hearts. Depressions of responsiveness were interpreted to occur on the basis of failure to restore positive and negative dP/dt to normal values and depressed coronary blood flow responses during adrenaline administration. Increases in coronary flow were regularly less in experimental hearts than the controls. Heart rate responses to adrenaline in both failing and non‐failing hearts were identical.
In conclusion, it is suggested that myocardial contractile and relaxation characteristics and coronary vascular responses to adrenaline infusion are depressed in endotoxin shock during the period of demonstrated myocardial dysfunction. No distinct causal relationships were observed between the altered myocardial responsiveness and pathogenesis of heart dysfunction since myocardial dysfunction and altered responsiveness to adrenaline were generally observed together. Myocardial oedema formation after endotoxin as previously reported by this laboratory may bear a relationship to the depressed negative dP/dt response to adrenaline.
ROLE OF CATECHOLAMINES IN THE CENTRAL MECHANISM OF EMETIC RESPONSE INDUCED BY PERUVOSIDE AND OUABAIN IN CATS
Authors: GAITONDÉ B.B. , JOGLEKAR S.N. 
Published: July 2012

Peruvoside, (a glycoside obtained from the plant, Thevetia neriifolia Juss) and ouabain produce emesis in cats. Vomiting is not produced by these drugs in animals pretreated with catecholamine depleting drugs like reserpine, tetrabenazine or syrosingopine. Chloropromazine hydrochloride, mepyramine maleate, or BOL‐148 administered intravenously or intracerebroventricularly do not afford protection.
Phenoxybenzamine produces partial protection against peruvoside‐induced emesis.
Haloperidol (1 mg/kg i.v.) prevents vomiting induced by peruvoside or ouabain. Intracerebroventricularly administered haloperidol is ineffective.
Cats pretreated with SKF‐525‐A, are not protected by haloperidol. Animals pretreated with phenobarbitone in a dose of 25 mg/kg for a week were protected by haloperidol, 250 μg/kg i.e. one quarter of the effective antiemetic dose in normal cats.
It is postulated that catecholamines are involved in the mechanism of vomiting induced by cardiac gycosides. Further, a metabolite of haloperidol seems to be responsible for its effective antiemetic action.
HYPERGLYCAEMIA PRODUCED BY DRUGS WITH ANALGESIC PROPERTIES INTRODUCED INTO THE CEREBRAL VENTRICLES OF CATS
Authors: DEY P.K. , FELDBERG W. 
Published: July 2012

The effects on blood glucose of four substances with analgesic properties (apomorphine, pethidine, codeine and etorphine) and of prostaglandin E1 were examined in unanaesthetized cats. They were applied by the intraventricular route being either injected into a lateral ventricle or infused into the fourth ventricle through implanted Collison cannulae.
Apomorphine gave rise to pronounced hyperglycaemia in a dose of 0.75 mg which produced scarcely any hyperglycaemia on intravenous injection. It was more effective on infusion into the fourth ventricle than on injection into a lateral ventricle and was approximately half as potent as morphine in provoking hyperglycaemia.
Codeine produced no hyperglycaemia in doses of 0.75 and 1.5 mg.
Pethidine had a weak hyperglycaemic action in doses of 0.75 and 1.5 mg, but the effect was not regularly obtained. Potency of the drug was at most only a third to a sixth that of morphine.
Etorphine produced strong hyperglycaemia on infusion into the fourth ventricle in a dose of 10 μg. Unlike apomorphine or morphine it was more potent on injection into a lateral ventricle when it produced a strong hyperglycaemic response in doses of 5 or 1 μg, which were subthreshold on infusion into the fourth ventricle. However, this response may have been brought about indirectly as a result of severe asphyxia and of convulsions associated with the injections. On infusion into the fourth ventricle, etorphine was about 75 times as potent as morphine in producing hyperglycaemia.
Prostaglandin E1 had no hyperglycaemic action when infused into the fourth ventricle in a dose of 400 ng.
ALTERNATIVE APPROACHES TO ANALGESIA: BACLOFEN AS A MODEL COMPOUND
Authors: CUTTING D.A. , JORDAN C.C. 
Published: July 2012

It is suggested that analgesia could be produced by drug action at the spinal level through (a) interference with neurotransmission at primary afferent terminals; (b) enhancement of the ‘gate control’ of the sensory input to the spinal cord mediated through descending spinal tracts; or (c) increased presynaptic inhibition of primary afferents by a direct action.
Baclofen (9.4–70.3 μmol/kg, i.p.), which may mimic spinal presynaptic inhibition, produced a dose‐dependent increase in the response times of mice in a hot‐plate test, but high doses also impaired motor function.
Morphine hydrochloride (5.3–40 μmol/kg, i.p.) increased the response time of mice in the hot‐plate test and had little effect on motor function.
Combination of baclofen (9.4 or 23.4 μmol/kg) with morphine (13.3 μmol/kg) produced greater increases in response time than either drug administered alone but with little concurrent effect on motor function.
The possibility that baclofen may have some analgesic action and a potentiating effect on other analgesics is discussed.
CHARACTERIZATION OF AN INHIBITORY RECEPTOR IN RAT HIPPOCAMPUS: A MICROIONTOPHORETIC STUDY USING CON‐FORMATIONALLY RESTRICTED AMINO ACID ANALOGUES
Authors: SEGAL M. , SIMS K. , SMISSMAN E. 
Published: July 2012

Pyramidal cells in rat hippocampus were used to study the molecular dimensions of a receptor for inhibitory amino acids in the central nervous system. The inhibitory potencies of γ‐aminobutyrate (GABA), β‐alanine and glycine were compared by standard microiontophoretic techniques. Subsequently, rigid cyclopentane and cyclohexane amino acid analogues were applied by iontophoresis and their relative efficacies were compared with those of the naturally occurring amino acids.
GABA was the most effective of the small aliphatic amino acids in producing inhibition of the firing of hippocampal pyramidal neurones. β‐Alanine was less effective and glycine was the least effective. GABA‐induced inhibition was antagonized by concurrent iontophoresis of picrotoxin or bicuculline, whereas strychnine did not antagonize GABA inhibition.
The ability of the series of substituted aminocyclopentane and aminocyclohexane carboxylic acids to produce inhibition of pyramidal cells was a direct function of the separation of amino and carboxylic acid groups. In both series of the cyclic amino acids the most potent inhibition was demonstrated when the spatial separation was similar to that of the extended GABA molecule (4.74 Å). Additionally, the inhibition of hippocampal pyramidal cells by (±)‐cis‐3‐amino‐cyclopentanecarboxylic acid, like that produced by GABA, could be blocked by simultaneous application of picrotoxin or bicuculline, but not by strychnine.
The present results suggest that the physiologically active conformation of GABA is the fully extended molecule, and additionally indicate that one dimension of the postsynaptic receptor site is within the range of 4.2 to 4.8 ångströms.
THE EFFECTS OF ADENOSINE TRIPHOSPHATE AND ADENOSINE DIPHOSPHATE ON TRANSMISSION AT THE RAT AND FROG NEUROMUSCULAR JUNCTIONS
Authors: RIBEIRO J.A. , WALKER J. 
Published: July 2012

The effects of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) were investigated on evoked end‐plate potentials (e.p.ps) and on miniature end‐plate potentials (min. e.p.ps) recorded from muscle fibres of the rat diaphragm and the frog sartorius.
ATP and ADP decreased the quantum content of the e.p.ps and the frequency of the min. e.p.ps. The maximum effects produced by the two substances were similar.
The potency of ATP was found to be similar to that of adenosine. In the presence of adenosine, in a concentration producing its maximum effect, the addition of ATP had no further effect. This is compatible with the idea that ATP acts in the same way as adenosine.
ATYPICAL TRYPTAMINE RECEPTORS IN SHEEP PULMONARY VEIN
Authors: EYRE P. 
Published: July 2012

Both the pulmonary artery and vein of the sheep contracted dose‐dependently to histamine, carbamoylcholine, prostaglandin F2α, noradrenaline and bradykinin and relaxed in the presence of isoprenaline or prostaglandin E1.
The effect of 5‐hydroxytryptamine (5‐HT) on the artery was consistently to produce dose‐dependent contractions without tachyphylaxis. The effect on the vein was biphasic. 5‐HT 5 × 10−10 to 5 × 10−8 M relaxed the partially constricted vein. 5‐HT 10−7 to 10−6 M caused brief venoconstriction followed by relaxation. 5‐HT > 10−6 M caused dose‐related contraction of the vein.
Methysergide effectively blocked the contractile response of the artery to 5‐HT, but only weakly inhibited the contractions of the vein (dose‐ratio <20).
Each of ten antagonists tested failed to inhibit the 5‐HT‐induced relaxation of the vein. Sheep pulmonary vein possesses tryptamine receptors which mediate relaxation and which are not of the classical M‐ or D‐type. These receptors appear not to be involved directly or indirectly with responses to acetylcholine, catecholamines, histamine or prostaglandins.
THE PHARMACOKINETICS OF PYRIDOSTIGMINE AND 3‐HYDROXY‐N‐METHYLPYRIDINIUM IN THE RAT: DOSE‐DEPENDENT EFFECTS AFTER PORTAL VEIN ADMINISTRATION
Authors: BARBER H.E. , BOURNE G.R. , CALVEY T.N. , MUIR K.T. 
Published: July 2012

The elimination kinetics of [14C]‐pyridostigmine iodide and [14C‐methyl]‐3‐hydroxypyridinium bromide (3‐OH NMP) have been studied in the rat.
For pyridostigmine, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that pyridostigmine is subject to metabolism during the first passage through the liver.
When doses of pyridostigmine 1.25 μmol/kg and higher were injected via the portal vein, the proportion excreted in urine as unchanged drug remained constant; in contrast, the percentage of the dose eliminated as the metabolite was significantly reduced. This indicates that a dose‐dependent process is involved in the urinary excretion of 3‐OH NMP.
This conclusion was supported by studies involving the portal and systemic venous injection of 3‐OH NMP at different dose levels. After 4 h, approximately 85% of the lowest dose was eliminated unchanged in urine; in contrast, only 63% of the higher dose was excreted during this period. The proportion of the dose eliminated in urine was not related to the route of administration.
After the injection of pyridostigmine into the jugular vein, the initial rate of drug excretion fell rapidly for approximately 10 min; in contrast, after injection into the portal vein, the rate of excretion of the drug rose to a maximum at 30 minutes. This suggests that the hepatoportal system behaves as a distinct region during the distribution of this drug.
ANTIARRHYTHMIC, HAEMODYNAMIC AND METABOLIC EFFECTS OF 3α‐AMINO‐5α‐ANDROSTAN‐2β‐OL‐17‐ONE HYDROCHLORIDE IN GREYHOUNDS FOLLOWING ACUTE CORONARY ARTERY LIGATION
Authors: MARSHALL R.J. , PARRATT J. R. 
Published: July 2012

The antiarrhythmic, haemodynamic and metabolic effects of a new amino steroid, ORG6001, have been investigated in experimental acute myocardial infarction in anaesthetized greyhounds.
ORG6001 administered either intravenously (1–10 mg/kg) or orally (50 mg/kg) significantly reduced the incidence of ventricular ectopic beats in the first 30 min after ligation of the left anterior descending coronary artery.
In dogs pretreated with ORG6001, metabolic changes indicative of myocardial ischaemia (lactate production and potassium efflux) were less marked than those occurring in control animals.
Antiarrhythmic doses of ORG6001 caused only minimal transient haemodynamic effects.
These results suggest that ORG6001 may possess distinct advantages over presently‐used antiarrhythmic drugs in the prevention and treatment of the early arrhythmias which occur after myocardial infarction.
ACTIONS OF PROSTAGLANDIN E2 ON MYOCARDIAL MECHANICS, CORONARY VASCULAR RESISTANCE AND OXYGEN CONSUMPTION IN THE GUINEA‐PIG ISOLATED HEART PREPARATION
Authors: KREBS R. , SCHRÖR K. 
Published: July 2012

In isolated, electrically driven (3 Hz) hearts of guinea‐pigs the action of prostaglandin E2 on left ventricular pressure (LVP), oxygen consumption (Qo2) and coronary vascular resistance (CVR) was studied by establishing cumulative concentration‐response curves. The hearts were perfused at a constant flow (10 ml/min) with Tyrode solution (Ca++ 1.8 mM) at 32° C.
Under control conditions prostaglandin E2 (2.86 × 10−11 − 1.43 × 10−7 M) decreased LVP, Qo2 and CVR in a concentration‐dependent manner by maximally 27, 18 and 38%, respectively (P < 0.05).
After reserpine pretreatment there were lower initial values for all parameters measured. The effect of prostaglandin E2 on LVP and Qo2 was abolished, but CVR was further diminished, depending on the concentration.
The results seem to support the hypothesis of an interaction of prostaglandin E2 with endogenous catecholamines as far as the effects on LVP and Qo2 are concerned. In contrast, prostaglandin E2 seems to have a direct action on CVR, which is independent of the presence of catecholamines.
NORADRENALINE AND MOTOR TRANSMISSION IN THE VAS DEFERENS OF THE MOUSE
Authors: JONES MARGARET E.L. , SPRIGGS T.L.B. 
Published: July 2012

A comprehensive investigation of the innervation of the vas deferens of the mouse was made using pharmacological, histochemical and electronmicroscopical techniques.
Guanethidine inhibited the response of the vas to transmural stimulation and potentiated the response to noradrenaline (NA). Phentolamine abolished responses to NA and to transmural stimulation.
After chemical sympathectomy degenerative changes were seen in presumptive noradrenergic axons; histochemical fluorescence due to catecholamines was absent. The vas failed to respond to transmural stimulation, and a 10‐fold increase in sensitivity of the vas to exogenous NA was observed.
NA is shown to diffuse slowly through this tissue whose muscle cells are densely packed. This is discussed in relation to the apparent ‘insensitivity’ of the vas to exogenous NA.
A cholinergic component was identified histochemically which did not contribute significantly to the motor response of the vas as chemical sympathectomy abolished completely the motor response elicited by transmural stimulation.
It is concluded that NA is the motor transmitter for the smooth muscle of the vas deferens of the mouse.
E. coli ENDOTOXIN SHOCK IN THE CAT; TREATMENT WITH INDOMETHACIN
Authors: PARRATT J.R. , STURGESS R.M. 
Published: July 2012

An earlier study had demonstrated that indomethacin, administered before E. coli endotoxin, abolished the initial pulmonary vasoconstriction and delayed the onset of the secondary shock phase that results from the intravenous injection of this agent in cats. The object of the present study was to determine whether indomethacin modified the shock phase when administered after endotoxin.
All the cats (whether or not they received indomethacin, 10 mg/kg) exhibited the characteristic features of the delayed shock phase that result from the administration of endotoxin (2 mg/kg). These included systemic hypotension, hypoglycaemia, reductions in arterial pH, cardiac output and systolic ejection time and an increase in arterial lactate. Five out of the ten animals given indomethacin survived 4 h compared with four out of twelve in the control (endotoxin alone) group.
These results do not support the suggestion that antipyretic‐analgesic drugs like indomethacin may be of benefit when given during bacteraemic or septic shock. They do support the suggestion that the acute pulmonary changes (hypertension and decreased compliance) that occur in this species within a few minutes of endotoxin administration ultimately contribute to the severity of the shock phase.
THE EFFECTS OF CATECHOLAMINES AND ADRENOCEPTOR BLOCKING DRUGS ON THE CANINE PERIPHERAL LYMPH FLOW
Authors: DE MICHELI P. , GLÄSSER A.H. 
Published: July 2012

Blood flow through the femoral artery, lymph flow in a lymphatic vessel in the femoral triangle and metatarsal distal venous pressure were measured simultaneously in a canine moving hind limb.
Low intra‐arterial doses of adrenaline and noradrenaline increased lymph flow even in the presence of marked arterial vasoconstriction. In contrast, isoprenaline increased arterial blood flow without affecting lymph flow rate.
Phenoxybenzamine, dihydroergotoxine, and nicergoline did not inhibit the lymphatic flow increase induced by adrenaline at doses active on arterial or venous vascular alpha‐adrenoceptors.
Propranolol given intra‐arterially into animals pretreated with alpha‐adrenoceptor blocking agents restored the vasoconstrictor effect of adrenaline (reversal of adrenaline reversal).
AN INDIRECT SYMPATHOMIMETIC EFFECT OF BURIMAMIDE ON KITTEN ISOLATED ATRIA
Authors: HOOD A.J.C. , SMY J.R. , WEETMAN D.F. 
Published: July 2012

Burimamide (34‐1080 μM) caused a concentration‐dependent increase in the force and frequency of contraction of kitten isolated atria.
Metiamide (467 μM) had no stimulant action on kitten atria and did not modify the effects of burimamide.
The atrial stimulation produced by burimamide was reduced by (‐)‐propranolol (34‐68 nM) and by cocaine (3 μM).
The atrial stimulant effect of burimamide was prevented by pretreatment of kittens with reserpine (1 mg/kg, 24 h before the experiment).
It is concluded that burimamide causes atrial stimulation by releasing catecholamines.
THE EFFECT OF RESERPINE ON HYPOTHALAMO‐PITUITARY‐ADRENOCORTICAL FUNCTION IN THE RAT
Authors: HODGES J.R. , VELLUCCI SANDRA V. 
Published: July 2012

The effect of reserpine on hypothalamo‐pituitary‐adrenocortical (HPA) function in the rat was investigated by the use of direct and indirect indices of pituitary adrenocorticotrophic activity.
Administration of a single dose of the drug induced prolonged hypersecretion of corticotrophin (ACTH).
Corticotrophin release in response to the drug no longer occurred after repeated daily injections, indicating that some form of ‘adaptation’ occurred.
The increase in HPA activity normally caused by exposure to cold was prevented by reserpine once ‘adaptation’ to the drug had been produced.
Inhibition of stress‐induced ACTH release was due neither to depletion of pituitary stores of the hormone, nor to a corticosteroid feedback effect.
INTERACTION OF HISTAMINE H1‐ AND H2‐RECEPTOR ANTAGONISTS WITH HISTAMINE UPTAKE AND METABOLISM BY GUINEA‐PIG ISOLATED ATRIUM AND MOUSE NEOPLASTIC MAST CELLS in vitro
Authors: FANTOZZI R. , FRANCONI FLAVIA , MANNAIONI P.F. , MASINI EMANUELA , MORONI F. 
Published: July 2012

Burimamide, metiamide, chlorpheniramine, triprolidine and cocaine, were tested as inhibitors of histamine uptake and metabolism in the guinea‐pig atrium and in mouse neoplastic mast cells.
Cocaine did not affect the uptake and metabolism of histamine, either in the atrium or in the mast cells. All the antihistamines tested blocked the uptake and metabolism of histamine in both preparations. The order of potency was burimamide > chlorpheniramine > triprolidine > metiamide in the atrium; and burimamide > metiamide > triprolidine > chlorpheniramine, in the mast cells.
Comparison of the present results with the antihistamine activity of these blocking agents suggests that no correlation exists between the receptor blocking activity and the ability of these substances to act as inhibitors of histamine uptake and metabolism.
ANTAGONISM OF ADENOSINE 5′‐TRIPHOSPHATE‐INDUCED RELAXATION BY 2‐2′‐PYRIDYLISATOGEN IN THE TAENIA OF GUINEA‐PIG CAECUM
Authors: SPEDDING M. , SWEETMAN A.J. , WEETMAN D.F. 
Published: July 2012

2‐2′Pyridylisatogen tosylate (PIT) (>2.5 μM) relaxed the guinea‐pig isolated taenia caeci by an unknown mechanism.
With higher concentrations of PIT (>12.5 μM) subsequent applications of adenosine 5′‐triphosphate (ATP) (2‐600 μM) revealed a blockade of the ATP receptors. The antagonism was characterized by a delayed onset of action (>10 min incubation with 50 μM PIT) and eventually became irreversible (>50 μM PIT for >30 minutes). The antagonism was specific for ATP, was not competitive, and was not dependent upon the relaxant effect.
The presence of either acetylcholine (0.05‐1.0 μM) or carbachol (0.05‐1.0 μM) increased the antagonistic effect of PIT (50 μM) approximately five‐fold.
Following prolonged exposure, PIT (50 μM for 90 min) did not block the inhibitory effects of field stimulation (2 Hz, 10 s) of the taenia caeci in the presence of hyoscine (0.33 μM). These results do not support the purinergic nerve hypothesis.
THE ACTION OF ACETYLCHOLINE ANTAGONISTS ON AMINO ACID RESPONSES IN THE FROG SPINAL CORD in vitro
Authors: NICOLL R.A. 
Published: July 2012

The isolated hemisected frog spinal cord has been used to study the action of acetylcholine antagonists on amino acid responses by means of sucrose gap recording.
Primary afferents and motoneurones were shown to contain few, if any, cholinoceptors, since acetylcholine and carbachol responses were essentially abolished when synaptic transmission was blocked with magnesium ions or when action potentials were blocked by tetrodotoxin.
Curare antagonized the γ‐aminobutyric acid (GABA) and β‐alanine depolarizations of primary afferents and the hyperpolarizing action of these amino acids on motoneurones. Nicotine also antagonized β‐alanine depolarizations and to a small extent GABA depolarizations of primary afferents. These actions are similar to but weaker than those obtained previously with picrotoxin.
Atropine selectively antagonized β‐alanine depolarizations of primary afferents and blocked β‐alanine and glycine hyperpolarizations of motoneurones. GABA responses were entirely resistant to the action of atropine. These actions are similar to but 50 times weaker than those obtained previously with strychnine.
Dihydro‐β‐erythroidine, tetraethylammonium, and gallamine were entirely ineffective in antagonizing amino acid responses. Since these agents are known to block the dorsal root potential elicited by ventral root stimulation but have no effect on the amino acid responses of primary afferents, it is evident that a cholinergic step is involved in this pathway.