Intravenous Injection Of Adrenaline Research Articles

Adrenergic receptors in amylase secretion from rabbit paratid gland

This study was made in order to discover which type of adrenergic receptor is concerned in the amylase secretion from rabbit parotid glands. The effect of sympathetic nerve stimulation and sympathomimetic agents on amylase secretion in response to stimulation of the auriculotemporal nerve was examined in relation to the actions of α and β receptor blocking agents. Cervical sympathetic nerve stimulation and intravenous injection of adrenaline, noradrenaline and isoprenaline caused an increase in amylase secretion; isoprenaline was about thirty times as potent as adrenaline and noradrenaline had three-quarters of the potency of adrenaline. Propranolol and dichloroisoprenaline (DCI) suppressed the increase in amylase secretion produced by sympathetic stimuli, while tolazoline and phenoxybenzamine di not. These results indicate that the sympathetic nervous system is important in amylase secretion and that the β receptors are the ones involved in this mechanisms. On the other hand, the initial acceleration of the salivary flow produced by sympathetic stimuli was specifically antagonized by α receptor blocking agents. The order of potency in the effect on salivary flow rate was adrenaline, noradrenaline and isoprenaline. These results indicate that the α adrenergic receptors are involved.

Der Einflu� mesencephaler Strukturen auf die phasische Blutdruckregulation

Experiments were performed on 45 cats. One group of animals was operated upon utilizing ether anesthesia which was discontinued after brain stem transsection. During the following experimental procedure the animals were immobilized with Flaxedil and artificially respired. Another series of experiments was carried out under Pentobarbital Sodium anesthesia (Nembutal). The brain stem was successively transsected according to the Horsley-Clarke coordinates A 2 (section I), P 2 (section II), and P 6 (section III). These sections are located rostrally to the rhombencephalic vasomotor center. Blood pressure elevations were produced by intravenous injection of adrenaline. The height of blood pressure did not change if mesencephalic structures were removed by the three sections. The duration of the adrenaline-induced rise in blood pressure was significantly prolonged after successive removal of the mesencephalic brain stem structures. This effect was abolished under Nembutal anesthesia. In this case the duration of the adrenaline-induced rise in blood pressure was found to be identical with the response to transsection in position III in unanesthetized cats. The increased duration of the adrenaline-induced blood pressure elevation after successive transsection of mesencephalic structures can still be observed after denervation of the carotid sinus bilaterally. Even though the differences observed were less pronounced, they remained statistically significant. Comparable results were obtained when both carotid sinus and depressor nerves were interrupted. If all buffer nerves including both vagi were cut, the duration of the rise in blood pressure continued to increase with each step of the mesencephalic transsection. In another series of experiments the rhombencephalic vasomotor center was isolated by deafferentiation from all buffer nerves and separated from higher brain stem structures by section III. The duration of an adrenaline-induced rise in blood pressure under these circumstances was not significantly longer than that observed after a subsequently performed spinal section at C1. In conclusion it can be said that mesencephalic brain stem structures are involved in the phasic regulation of blood pressure. The results of the experiments suggest that the baroreceptor reflex arc sends collaterals to the mesencephalon. Since a less pronounced mesencephalic influence on blood pressure regulation can still be observed after deafferentiation from all buffer nerves, the conclusion is reached that additional pressosensitive structures within the mesencephalon participate in the regulation of blood pressure. Application of barbiturates induces complete blockage of the described mesencephalic influence on blood pressure regulation.

Rôle of adrenergic factors in the production and perpetuation of atrial flutter in the dog.

The rôle of adrenergic factors in the production and perpetuation of atrial flutter has been studied in dogs under pentobarbitone sodium anaesthesia. The adrenergic influence was (a) increased by sympathetic stimulation or by intravenous injection of adrenaline and noradrenaline and (b) decreased by depletion of cardiac stores of catecholamines by previous treatment of the animals with reserpine.Sympathetic stimulation, as well as adrenaline and noradrenaline increased the atrial rate in aconitine‐induced and post‐stimulatory atrial flutter, and in some cases the flutter was converted into fibrillation. Atropine sulphate only partially blocked the increase in flutter rate, but atrial fibrillation never occurred after atropine administration.In some cases of aconitine‐induced atrial flutter, as the peak effect of adrenaline was passing off the atrial rate fell below that of sinus rhythm for a few seconds, and then gradually increased to the control level. No such response was seen after noradrenaline administration.When cardiac stores of catecholamines were depleted by previous treatment of the animals with reserpine, aconitine produced long‐lasting atrial fibrillation in all the experiments. Atropine injection converted atrial fibrillation into slow rate atrial flutter. In such animals, electrical stimulation produced transient atrial fibrillation, the rhythm returning to normal sinus rhythm, a few seconds to a few minutes after the stimulation ceased. It was not possible to induce stable atrial flutter despite repeated attempts, and even after the administration of atropine.The mechanism of these findings is discussed.

The role of adrenergic receptors in cardiovascular changes associated with exercise in salmon

1. 1. Intravenous injections of epinephrine produced an increase in dorsal aortic blood pressure and heart rate. Low dose levels of epinephrine caused a reflex slowing of the heart, a response abolished by atropine injections into the pericardial cavity. 2. 2. Phenoxybenzamine injections blocked the pressor response to epinephrine. Changes in blood pressure during activity and excitement also disappear after α-adrenergic receptor blockage with phenoxybenzamine. 3. 3. It is concluded that there are α-adrenergic receptors in blood vessels in the gills and in the general body circulation. Epinephrine probably causes a vasodilation in the gills and a vasoconstriction of blood vessels peripherally in the systemic circulation. 4. 4. Blood pressure changes occuring during swimming can be explained by the interaction of epinephrine with α-adrenergic receptors. 5. 5. Dichloroisoproterenal or propranolol, when injected intravenously in fish, had little effect on the response of the heart to epinephrine, but caused a marked fall in dorsal aortic blood pressure and heart rate.

Sympathetic Blocking Action of Iproniazid in the Unanesthetized Dog

Iproniazid, on intravenous injection in the unanesthetized dog, inhibited the increase in arterial blood pressure resulting from the intravenous injection of epinephrine, DMPP, and tyramine. Adrenergic blockade appeared to be an important factor in this action of iproniazid, although the possibility of inhibition of the release of norepinephrine from nerve terminals could not be eliminated. These results confirm in vitro studies of previous investigators.

EFFECT OF PROPRANOLOL ON CATECHOLAMINE-INDUCED ARRHYTHMIAS DURING NITROUS OXIDE-HALOTHANE ANAESTHESIA IN THE DOG

SUMMARY In dogs under nitrous oxide-halothane anaesthesia, ventricular arrhythmias were produced by intravenous injection of adrenaline and noradrenaline 2–3 μg/kg or isoprenaline 1μg/kg, and completely prevented by propranolol 0.3 mg/kg. Adrenaline or noradrenaline (20–30 μg/kg) produced slow rate ventricular extrasystoles and ventricular bigeminy, without increase in the rate of sinus rhythm. Doses of 100 to 150 μg/kg produced ventricular tachycardia in all and ventricular fibrillation in some experiments. Increase in sinus rate always preceded ventricular tachycardia. Isoprenaline 10 μ/kg produced ventricular tachycardia preceded by an increase in sinus rate. Very large doses (50 μg/kg) produced a greater increase in sinus rate, and later ventricular tachycardia and even ventricular fibrillation resulted in all the experiments. Dosages of catecholamines which did not produce any increase in the rate of sinus rhythm never produced ventricular tachycardia or fibrillation.

The effect of adrenaline on the secretion and amylase content of parotid saliva in man.

The effect of slow intravenous injection of adrenaline on the volume flow and amylase content of parotid saliva in man was studied in three subjects. Saliva was collected by suction cups. Rate of salivary flow and amylase concentration varied widely between individuals and in any one individual from day to day. Adrenaline, at rates of injection of 6 and 3 μg per minute, consistently decreased the volume flow, but increased the concentration of amylase, in parotid saliva. The rate of secretion of amylase (the product of rate of salivary flow and concentration of amylase) remained relatively constant.

Oxytetracycline and hypoglycemia with convulsions in pancreatectomized dogs.

SummaryAddition of oxytetracycline to intravenous fluid used to maintain pancrea-tectomized dogs brings about a state of hypo-glycemia with staggering and convulsions that only infrequently responds to administration of glucose. The liver glycogen of these dogs is usually normal and occasionally elevated. During the state of hypoglycemia with staggering and convulsions the rise of the blood glucose following intravenous injection of adrenalin or glucose (glucose tolerance test) is transient; the rise of the blood glucose following intravenous injection of glucagon is large and sustained.

Urinary excretion of adrenaline metabolites in man during intervals of 2 minutes, 5 minutes, and 10 minutes after intravenous injection of adrenaline

Six subjects were injected i.v. within 1 min with 4.8 μc (34 μg) of DL-adrenaline-2- 14C. The urine was collected via an indwelling catheter at 2 min and 5 min after injection and thereafter at 10-min intervals for 1 hr, and continued for 6 and 24 hr. Urinary adrenaline and its metabolic products were separated and identified by means of column fractionation and paper chromatography. The radioactivity of each metabolite was measured by liquid scintillation. The basic metabolites, including adrenaline, are metadrenaline and an unknown. The acidic metabolites are: 3-methoxy-4-hydroxy-phenylglycol; 3,4-dihydroxyphenylglycol; sulfate conjugate of metadrenaline; glucuronic acid conjugate of metadrenaline; 3-methoxy-4-hydroxymandelic acid; 3,4-dihydroxymandelic acid; 3-methoxy-4-hydroxyphenylacetic acid; 3,4-dihydroxyphenyl-acetic acid; 3-methoxy-4-hydroxybenzoic acid; 3-methoxy-4-hydroxyphenylglycol sulfate; 3,4-dihydroxyphenylglycol sulfate and several unknowns. No radioactivity was recovered during the 0 to 2-min post injection period. However, the highest percentage of recovered adrenaline and 3,4-dihydroxymandelic acid appeared in the 2 to 5-min postinjection period. The greatest amount and the highest percentage of radioactivity recovered as metadrenaline appeared 5 to 10 min after injection. In terms of total radioactivity the amounts of adrenaline, metadrenaline, and 3,4-dihydroxymandelic acid so rapidly decline that by 30 min after injection these compounds each represent less than 3.5 per cent. Concomitant with this decline there is a rapid increase in the radioactivity of 3-methoxy-4-hydroxymandelic acid such that by 20 min after injection it represents more than 50 per cent of the total radioactivity found in the urine; after 40 min this metabolite begins to decrease. There is a gradual increase in the metadrenaline sulfate; in the 6 to 24 hr period it represents 53.0 ± 1.6 per cent of the total radioactivity. The importance of understanding the early formation of these adrenaline metabolites is emphasized, and the probable mechanisms involved in the metabolism and inactivation of circulating adrenaline are discussed.

Some cardiovascular and central actions of a group of potent propionanilide analgesics

Several phenylpiperidine propionanilide analgesic agents and some related compounds produced hypotension and bradycardia, potentiated vasoconstrictor responses to epinephrine, and unmasked an intense reflex bradycardia following intravenous injection of epinephrine. The data suggest that hypotension did not result from direct vascular or cardiac effects of the drugs, nor from a drug induced release of histamine. The decrease in heart rate and the unmasking of reflex epinephrine bradycardia were attributed to a CNS action which could be blocked by vagotomy or by atropine. The pattern of cardiovascular action of morphine resembled, and that of meperidine and histamine differed from that of propionanilide agents; particularly, unmasking of reflex epinephrine bradycardia was absent with meperidine and histamine. The order of potency of the different analgesics tested, including morphine but not meperidine, was similar whether determined by the capacity of the drugs to unmask epinephrine bradycardia, to produce plastic rigidity in the rat, or analgesia in the mouse. The most active member of the series, N-[1-Methyl-2-(4-hydroxy-4-phenyl-1-piperidyI) ethyl] propionanilide oxalate (compound MA-1466), was about 10,000 times more potent than morphine in unmasking epinephrine bradycardia, about 1000 times more potent in producing plastic rigidity, and about 100 times more potent in a bio assay of analgesic activity.

THE EFFECT OF SYMPATHOMIMETIC AMINES ON FEMORAL ARTERIAL BLOOD FLOW IN THE CAT

Abstract : Changes in the blood flow through the unopened femoral arteries of anaesthetized cats after the local intra-arterial and intravenous injection of adrenaline, noradrenaline, phenylephrine, metaraminol, methylamphetamine, mephentermine, methoxamine and isoprenaline have been determined by an electromagnetic method. The simultaneous recording of mean aortic pressure enabled changes in femoral vascular resistance to be calculated. Local intraarterial injection of isoprenaline reduced, while noradrenaline, phenylephrine, metaraminol, methoxamine and methylamphetamine increased, femoral vascular resistance. Adrenaline and mephentermine produced variable resistance changes. Those agents which increased femoral vascular resistance when given intra-arterially frequently reduced resistance when given intravenously. This reduction accompanied the rise in systemic arterial pressure, but in many animals adrenaline, noradrenaline, phenylephrine and metaraminol frequently induced a further reduction in resistance as the pressor effect declined. These observations are discussed in relation to the current theories of the mechanism of vasodilatation produced by sympathomimetic amines. (Author)

ENHANCEMENT OF FIBRINOLYSIS IN THE DOG BY INJECTION OF VASOACTIVE DRUGS.

Intravenous injection of epinephrine into the dog produces an increase in fibrinolytic activity of plasma euglobulins. This increase appears to be unrelated to the following epinephrine-induced effects: splenic contraction, stimulation of the lymph circulation, increase in blood glucose, lactic acid, or free fatty acids. A specific involvement of either alpha or beta adrenotropic receptors is ruled out since norepinephrine and isopropylnorepinephrine are equally effective in enhancing fibrinolysis. Intravenous injection of each of a number of vasoactive drugs with different modes of action, and with either hypertensive or hypotensive properties, induces an increase in fibrinolytic activity. Hence, it appears that there is a direct relationship between appearance of increased fibrinolytic activity and vasoactive changes. For all the drugs tested except methoxamine, the maximal fibrinolytic effect is present 5 min after the injection and in general the fibrinolytic activity returns to the preinjection level within 30 min. Repeated injections of a powerful inducer of increased fibrinolytic activity, such as histamine, results in a progressive decrease of the fibrinolytic response.

On the mechanism for accelerating blood coagulation in dogs associated with intravenous injection of adrenalin

In experiments staged on 16 dogs an inquiry was made into the effects of intravenous adrenaline injections (0.15 mg/kg) on the functional state of the blood coagulative system. Venous blood procured prior to and 5, 30, and 60 minutes after adrenaline injection was tested. Under the effect of adrenaline blood coagulation time (in vitro) and silicon blood coagulation time are halved, whereas the plasma heparin tolerance almost doubles. Prothrombin blood activity and fibrinogen concentration show no statistically authentic change. Blood antithrombin activity diminishes almost by 50%. Blood fibrinolytic activity shows a considerable rise.

Sweat Gland Function in the Ayrshire Calf

The sweat glands of the Ayrshire calf have been stimulated by heat and by adrenaline. Skin specimens were taken by biopsy before and at intervals after stimulation, to enable any subsequent cycle of secretion to be timed. Evidence for the functional ability of the sweat glands was obtained after intravenous injection of adrenaline, which caused visible sweating, and also after exposure to heat which resulted in a measurable reduction in glandular volume after prolonged exposure. After stimulation, however, the sweat glands always had a flat epithelium, were never devoid of secretory material and failed to exhibit sequential stages of secretion. Even an intradermal injection of 1.0 ml. of 10−3 g./ml. of adrenaline which caused intense vasoconstriction, depigmentation of the hairs, increase in the thickness of the glandular epithelium and subsequent degeneration of the cells failed to remove all the secretion from the glands. Weaker concentrations administered intradermally failed to produce a sweating response or to cause a change in the appearance of the glands. It is concluded that the sweat glands in Bos taurus are functional organs which respond to heat and to adrenaline in a manner which does not involve sequential stages of secretion. They do not conform to the classification of Schiefferdecker (1917)

The influence of the adrenal medulla on the response of the gastric glands to painful stimulation

The part played by the adrenals in the response of the gastric glands to painful stimulation was studied in dogs with Pavlov and Heidenhain pouches. Both painful stimulation and intravenous injection of epinephrine induced similar quantitative and qualitative changes of the gastric juice. Reflex secretion of epinephrine into the blood was prevented by removal of the right and denervation of the left adrenal gland, and it was then found that painful stimulation caused only insignificant and transitory changes of the gastric secretion. We therefore think that the adrenals participate in the response of the gastric glands to painful stimulation.

The functional activity and control of the apocrine sweat glands of the scrotum of the ram

When scrotal skin temperature was raised to above 35.3°C, the large glands of the scrotum discharged sweat synchronously at intervals of 2–14 min in eight rams and 9–40 min in one ram. Evaporation of the sweat when the wool on the scrotum was short caused sharp falls in skin temperature of up to 2.6°C; when wool was 18–30 mm long, skin temperature first rose and then fell to either the pre-discharge temperature or just below. Local anaesthesia of the superior perineal nerves abolished the sweat gland response to heat. Although single intravenous injections of adrenaline (1–4 µg /kg) and noradrenaline (1–6 µg /kg) were followed by single sweat gland discharges, bilateral adrenalectomy with replacement of adrenal cortical hormones did not prevent gland discharges in response to heat. The appearance of the first discharge in the adrenalectomized ram was delayed, and the delay was reduced by constant infusions of 0.8–1.0 µg adrenaline /kg/min. Partial lumbar sympathectomy changed the pattern of discharges and reduced the amount of fluid ejected at each discharge. It is concluded that adrenergic sympathetic nerves control the expulsion of sweat in response to heat, but that hormones from the adrenal medulla may also play a part. The control of sweating by cutaneous temperature receptors and its relationship to the possible control exerted by receptors in the brain are discussed in the light of these findings.

Arousal reaction in EEG induced by blood pressure.

IT is supposed by several authors1–9 that adrenaline-induced EEG-arousal, which originates in the mesencephalic reticular formation and the posterior hypothalamus, is caused by a direct action of adrenaline on these structures. Discharges were recorded from single cells within the posterior hypothalamus10,11. The firing-rate of these cells was affected by intravenous injection of adrenaline or by mechanically induced changes of blood pressure. There is no effect of adrenaline if the blood pressure is kept constant artificially. We therefore tested the hypothesis that the adrenaline-induced arousal is a secondary effect of the rising blood pressure.

Neurovascular control of oxygen tension in the testis and epididymis.

Summary. Interstitial oxygen tension was recorded polarographically with gold-plated needle electrodes in the testis and cauda epididymidis of the rabbit, sheep and dog. The mean epididymal resting oxygen tension was about twice that of the testis in the rabbit and sheep, and nearly three times testis oxygen tension in the dog. A short period of oxygen breathing doubled testicular oxygen tension while nitrous oxide breathing more than halved it. The latency of the testis response was always much longer than that of the epididymal response in the rabbit and sheep, but only slightly longer in the dog. The discrepancy was accounted for by the arterial arrangement in the three species. Occlusion of the internal spermatic artery produced a drastic fall in testis oxygen tension in the rabbit, sheep and dog, and had little effect on epididymal oxygen tension. Vasal artery occlusion reduced oxygen tension in the cauda epididymidis but not the testis, and a large fall occurred only if collateral vessels from the internal spermatic or cremasteric arteries were also clamped. Circulatory hypotension produced by amyl nitrite inhalation reduced oxygen tension in the testis and epididymis of all three species. Local cooling of the scrotum depressed oxygen tension in the ipsilateral testis of the rabbit, sheep and dog. Conversely, local warming of the scrotum produced a rise of oxygen tension in the ipsilateral testis. Thoraco-lumbar spinal anaesthesia did not block these effects. Electrical stimulation of the sympathetic areas of the hypothalamus in the rabbit elicited a profound depression of testicular oxygen tension characterized by an initial rapid phase, which was abolished by posterior mesenteric ganglionectomy and hypogastric nerve section, and a secondary slower phase, which was abolished by adrenalectomy. The two phases could be mimicked by stimulation of the posterior mesenteric ganglion or hypogastric nerves, and by intravenous injection of adrenaline respectively.

Maternal influences on fetal cardiovascular system in the sheep, dog, and rabbit.

Continuous recordings of the fetal carotid artery blood flow, blood pressure, heart rate; renal, brain, uterine, and cotelydon blood flow; and maternal carotid artery blood pressure and heart rate were made during and after varied types of maternal stimulations and chemical injections in three anatomically different types of placental-uterine-fetal arrangements as exemplified by the sheep, dog, and rabbit. Included in this series was pinching of the ear, eyeball pressure, asphyxia, pure tones, stroking of the viscera, vagal stimulation, and intravenous injection of epinephrine, norepinephrine, acetylcholine, serotonin, and sodium pentobarbital. In all three animal species the fetal physiological responses were, in general, the same for any particular type of maternal stimulus or chemical injection. Fetal carotid artery blood flow together with fetal renal and brain blood flow were the most reliable indicators of fetal response to any particular maternal influence, with fetal blood pressure next and fetal cardiac rate the least reliable. Fetal renal and brain vasculature responded in the same qualitative manner to all maternal influences, whereas fetal carotid artery blood pressure and flow and cardiac rate were variable in their responses. All fetal responses were distinguished by their long duration, especially the renal and brain vascular responses.

Histopathology of the nervous elements in the heart and the aorta of dogs after intravenous injection of adrenalin and caffeine

Repeated intravenous injections to dogs adrenalin (1: 1000 solution) with caffeine (1% solution) in a dose of 1 ml provoke severe injuries of the intramural nervous system of the heart. These derangements are manifested in progressive destruction of the nerve fibers of all calibers as well as of the sensory nerve endings. Irritation phenomena appearing in some of the nerve cells of the intracardiac ganglia after 2–3 injections, are later replaced by pyknosis if these injections are continued. There was focal interstitial myocarditis, and proliferative connective tissue reaction in the aortic wall. No histopathological changes in the myocardium, nervous elements of the heart or aorta were detected in control animals to which these substances were injected subcutaneously.