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Effect of beta-adrenergic receptor antagonism on chloralose-induced hemodynamic changes in newborn lambs.

alpha-Chloralose is an anesthetic commonly used in cardiovascular research. Using a chronically instrumented neonatal lamb model, we previously determined that chloralose has important effects on basal hemodynamics and arterial oxygen tension as compared with those of paired conscious control lambs. We wished to determine whether beta-adrenergic receptor stimulation accounted for chloralose-induced hemodynamic effects and to investigate the influence of chloralose and beta-adrenergic receptor antagonism on oxygen metabolism. In paired studies, five lambs were given chloralose intravenously (30 mg/kg i.v.) after propranolol (1 mg/kg i.v.) or saline control. The group pretreated with propranolol had reduced heart rate (HR 206 +/- 12 vs. 244 +/- 10 beats/min, p = 0.04) and cardiac output (CO 253 +/- 29 vs. 302 +/- 40 ml/min/kg, p = 0.005) 30 min after chloralose as compared with control; pretreatment with propranolol also attenuated the systemic hypertensive response to chloralose (77 +/- 8 vs. 89 +/- 5 mm Hg, p = 0.055). No difference in the response of stroke volume (SV), atrial or pulmonary arterial pressures, or pulmonary and systemic vascular resistances (PVR, SVR) were observed between treatment groups. No differences between propranolol and saline treatment groups were observed in arterial and mixed venous oxygen contents, arteriovenous (A-V) oxygen difference, oxygen extraction, or oxygen consumption; a reduction in oxygen delivery observed after propranolol as compared with saline was not altered by chloralose. We conclude that tachycardia and increase in CO induced by chloralose in lambs probably are mediated by beta-adrenergic receptor stimulation, which may be direct or indirect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists

Comparative effects of chloralose anesthesia and Sernylan analgesia on cerebral blood flow, CO2 responsiveness, and brain metabolism in the baboon.

A comparison was made between the effects of two different anesthetics, alpha-D-gluco-chloralose and 1-1-phenylcyclohexyl piperidine hydrochloride (Sernylan), on cerebral blood flow (CBF), brain metabolism and cerebrovascular CO2 responsiveness in primates. The experiments were carried out on immobilized and artificially ventilated baboons. Anesthesia was induced either with 100/mg/kg chloralose (i.p.) or with 1 mg/kg Sernylan (i.m.). CBF in 8 different brain regions was measured by the intra-arterial 133Xe clearance technique. The CO2 responsiveness of the cerebrovascular bed was tested by a gas mixture containing 5% CO2. Chloralose depressed total as well as regional CBF compared to the effect of Sernylan. A significant shift occurred toward lower CBF values in the grey matter while white matter flow was identical in the two groups. Brain O2 consumption was significantly higher during Sernylan analgesia (3.35 +/- 0.34 ml/100 g/min) than during chloralose anesthesia (2.42 +/- 0.22 ml/100 g/min). There were no differences in glucose uptake, lactate and pyruvate production, or in arterial and cerebral venous blood gases in the two types of anesthesia. The cerebrovascular CO2 sensitivity of the Sernylan-treated baboons was higher than that of the chloralose-anesthetized animals, in both the grey and white matter.

Animals

[Possible chloralose poisoning in buzzards (author's transl)].

The use of alpha-chloralose in poisoned eggs is conditionally permitted in the control of Corvidae. Chloralose does not have a selective action. Poisoning occurs in other egg-eating animals (hedgehogs) and, indirectly, in carrion-eating predators which prey on these unintended victims. A tentative diagnosis of alpha-chloralose poisoning in three buzzards (Buteo buteo) was based on the history, the clinical picture (identical with that in magpies with known chloralose poisoning), the complete recovery and the exclusion of other diseases. Other methods for the control of Corvidae are advocated.

Animals

Pulmonary and systemic hemodynamic effects of delta9-tetrahydrocannabinol in conscious and morphine--chloralose-anesthetized dogs: anesthetic influence on drug action.

Pulmonary and systemic hemodynamic effects of delta 9-tetrahydrocannabinol (delta 9-THC) in conscious dogs and in those anesthetized with morphine (3 mg/kg, i.m.) plus alpha-chloralose (100 mg/kg i.v.) were evaluated in this study. A decrease in the heart rate, cardiac output (PBF) and a concomitant increase in the pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW) observed in conscious animals following the administration of delta 9-THC were qualitatively similar to the effects reported in dogs anesthetized with sodium pentobarbital; however, unlike in the pentobarbital group, hypotensive effects to THC were not evident in the consious animals. In contrast, the effect of delta 9-THC in morphine--chloralose dogs were different; in this group delta 9-THC administration resulted in increases in the heart rate the PBF, and significant reductions in PAR, PVR and RVSW. Further, a decrease in the arterial blood pressure noted following THC administration was closely associated with a reduction in the total peripheral resistance in the morphine--chloralose group. The results of this study indicated that the pulmonary effects of THC in dogs may be related to its actions on the heart rate and differ qualitatively as well as quantitatively depending on the anesthetic used.

Anesthetics

Renal vascular response to haemorrhage in the rabbit after pentobarbitone, chloralose-urethane and ether anaesthesia.

1. Total renal blood flow and its cortical distribution were measured by the microsphere technique before and after haemorrhage in conscious rabbits, and after haemorrhage in rabbits anaesthetized with pentobarbitone, chloralose-urethane or ether. 2. The average blood loss necessary to achieve a fall in systolic blood pressure to about 65 mmHg was 101 ml in conscious rabbits and 38, 90 and 118 ml in weight-matched groups of rabbits anaesthetized with pentobarbitone, chloralose-urethane and ether respectively. 3. After haemorrhage in conscious rabbits total renal blood flow fell by 25%, this fall being confined to the superficial renal cortex. 4. In rabbits subject to haemorrhage under pentobarbitone anaesthesia renal blood flow fell by a further 23% when compared with the conscious bled rabbits. This reduction in blood flow was confined to the superficial cortex. 5. Haemorrhage in the rabbits subjected to chloralose-urethane anaesthesia caused no significant change in renal blood flow, as compared with conscious bled rabbits. 6. Haemorrhage under ether anaesthesia was associated with a further 33% fall in total renal blood flow, as compared with conscious bled rabbits. This was associated with a fall of 32% and 34% in superficial and deep cortical blood flow respectively. 7. Animals subjected to general anaesthesia may be particularly susceptible to the renal haemodynamic effects of haemorrhage.

Anesthesia, General

The effects of pentobarbitone and chloralose anaesthesia on the vagal component of bronchoconstriction produced by histamine aerosol in the anaesthetized dog.

1 Total lung resistance (R(L)) and dynamic lung compliance (C(dyn)) were measured in dogs anaesthetized with pentobarbitone or chloralose and subjected to aerosols of histamine during 4 successive inspirations.2 Histamine caused concentration-dependent increases in R(L) and decreases in C(dyn). A significant vagal component was involved, but only when chloralose was employed and then only in the R(L) response.3 The resting values of R(L) and C(dyn) were similar regardless of which anaesthetic was used and remained essentially the same if the vagi were cooled.4 Electrical stimulation of the efferent vagi caused large increases in R(L) of dogs given chloralose and these effects were attenuated by the administration of pentobarbitone. Such stimulation was relatively ineffective in dogs given pentobarbitone alone.5In vitro, electrical field stimulation caused contractions of dog trachealis muscle. The responses were reduced by pentobarbitone in concentrations approximating to plasma levels in the anaesthetized dogs (1 to 5 x 10(-4) M), but the effects of exogenous acetylcholine were unaltered. The inhibition was dose-dependent, reversed by washing and unaltered by hexamethonium.6 The results suggest that pentobarbitone inhibits the vagal component of histamine-induced bronchoconstriction in the dog by an action on the efferent pathway. Furthermore, pentobarbitone acts either by blocking transmission along postganglionic parasympathetic nerves or by preventing the release of acetylcholine from the nerve endings in the lung.

Aerosols

Alterations in blood sugar, serum insulin and circulating free fatty acid responses to glucose load produced in dogs by chloralose anaesthesia.

The effects of chloralose anaesthesia on the BS, serum IRI and circulating FEA responses to glucose in dogs, in the course of glucose tolerance tests were studied. Chloralose induced a moderate glucose intolerance, and abolished both, the insulin response to hyperglycaemia in these animals and the lipolytic response at the end of the test. These effects indicate that chloralose anaesthesia is definitely improper for metabolic studied in experimental biology.

Anesthesia

[Toxicologic analysis of chloralose. Application to 3 cases of acute intoxication].

The authors describe the study of three human intoxication case by chloralose. The detection and dosage of the toxic in the urine of patients have been carried out by the mean of a technic perfected by the same authors. In two case, it has been possible to trace the elimination of the toxic in the urine, the data relative to the third case were not sufficiently precised but they enable to show the existence of criminal etiology of chloralose.

Adult

[The effect of methohexital, fentanyl, droperidol, and chloralose on the aortic baroceptor discharge of decerebrated cats (author's transl)].

The effect of methohexitone, fentanyl, droperidol and chloralose on the response characteristics of aortic barorecptors was studied in decerebrated cats. The conclusions rest on the analysis of the drug effect on the stimulus-response curves of individual baroceptor fibres of the aortic region relating the average discharge rate (spike/s) to the average aortic arch pressure which was altered over wide ranges by a balloon catheter located in the thoracic aorta. The stimulus response curves were shifted to higher activities by methohexitone and less obviously also by droperidol. Contrarywise, chloralose and fentanyl shifted these curves to lower activities. Thus, the first two drugs increase the afferent receptor drive and favour the development of arterial hypotension, whereas the last two decrease the afferent receptor drive and act to stabilize the arterial pressure. Interestingly, at comparable depth of anesthesia arterial blood pressure levels tend to be lower with the first kind of anaesthetics as compared with the last.

Animals

Chloralose induced alteration of visually evoked response from specific and non-specific regions of cat neocortex.

Visually evoked response (VER) and EEG from the motor cortex (precruciate gyrus) and the visual cortex (marginal gyrus) of cats were recorded from 4 to 7 h after the injection of anesthetic doses of alpha-chloralose. During the recording period the VER from the precruciat gyrus showed a 200-300% increase in amplitude while the VER from the marginal gyrus rarely varied more than 50% in amplitude, and did so independent of the changes in the VER from the precruciate gyrus. The number of large amplitude spikes in the EEG from the precruciate gyrus also increased dramatically during the recording period, but no definite correlation between changes in VER amplitude and in the number of spikes in the EEG could be demonstrated. These observations suggest a functional separation between specific and nonspecific sensory pathways, with the latter showing a considerably greater sensitivity to level of anesthesia.

Animals

Comparison of the effects of pentobarbital and chloralose on the cardiac rhythms of the dog in chronic atrio-ventricular heart block.

In the dog in chronic atrio-ventricular dissociation, pentobarbital at a dose of 25 mg/kg causes atrial tachycardia, but does not change the ventricular frequency. The vagolytic effect of pentobarbital explains this phenomenon. The pronounced vagal tonus seen in the Keith-Flack node, is not seen in the ventricle. Chloralose at a dose of 80 mg/kg i.v. does not alter atrial frequency but depresses ventricular frequency, in a significant way, for 40 min.

Animals

Central cardiovascular effects of phentolamine in chloralose-anesthetized cats.

Phentolamine (50, 100 and 200 microng/min for 30 min) perfused through the cerebroven system of chloralose-anesthetized cats produced dose-related reductions in tricular blood pressure. Evidence is presented which suggests that this hypotensive activity was due to an interaction at central nervous system sites and was not attributable to escape of the compound from the brain. Centrally administered phentolamine was more effective in lowering blood pressure than the i.v. infusion of phentolamine at a dose (25 microng/kg/min for 30 min) which markedly antagonized peripheral alpha-adrenoceptors. In addition, central phentolamine induced bradycardia in contrast to the tachycardia which accompanied i.v. administration. By limiting the perfusion of phentolamine to selected portions of the cerebrospinal fluid spaces a major site of action responsible for the hypotensive activity was located outside the ventricles in an area accessible from the subarachnoid spaces. A second, less important site, anterior to the midbrain adjacent to the ventricular system apparently contributed to the hypotension. Phentolamine, introduced centrally, also impaired reflexogenic bradycardia elicited by pressor doses of norepinephrine. Both the sympathetic withdrawal and the vagal activation which account for this reflex seemed to be antagonized by phentolamine.

Anesthesia

Intrathecal tolerance of metrizamide in chloralose anesthetized cats.

The water soluble radiopaque medium, metrizamide (Amipaque) was introduced into the lumbar subarachnoid space in chloralose anesthetized cats at a standard volume of 0.35 cc/kg in concentrations of 300 mgI/cc to 500 mgI/cc during EMG recording. These animals did not differ from controls which received cerebrospinal fluid under otherwise identical conditions; both groups usually showed some mild and occasional muscle fasciculations or mild spasms. Treatment with metrizamide appeared to be a less deleterious procedure than that using hyperosmotic sucrose (1.32 M) as judged from EMG records. In contrast, equivalent amounts of neglumine iothalamate produced frank convulsions in 7 of 15 cases and a range of hyperirritability in the remaining 8.

Anesthesia

Effects of acute and chronic paleocerebellar stimulation on experimental models of epilepsy in the cat: studies with enflurane, pentylenetetrazol, penicillin, and chloralose.

Effects of acute and chronic paleocerebellar stimulation were evaluated in four experimental models of epilepsy in 24 adult cats chronically implanted with bilaterally symmetric parasagittal electrocorticographic electrodes and anterior lobe cerebellar stimulation electrodes. Pentylenetetrazol was given intraveneously in 50-mg increments or 4% enflurane was inspired until grand mal seizures occurred spontaneously or were triggered by photic or auditory stimuli. Alpha-chloralose, 50 mg/kg, was injected intraperitoneally to produce a model of stimulus-sensitive myoclonus and sodium penicillin G, 350,000 units/kg, was injected intramuscularly to produce a model of petit mal epilepsy. One- to 250-Hz electrical stimulation of paleocerebellar cortical surfaces was performed with constant-voltage or constant-current stimulators at threshold and suprathreshold intensities with average intensities of 8 V and 2.5 mA, respectively. Acute or chronic, threshold or suprathreshold paleocerebellar stimulation did not predictably alter the electrographic or clinical manifestations in any of these four models.

Acoustic Stimulation

Effects of afferent volleys from the limbs on the discharge patterns of interpositus neurones in cats anaesthetized with alpha-chloralose.

1. In cats anaesthetized with alpha-chloralose, micro-electrodes have been used to record the discharge patterns of single neurones in the region of the nucleus interpositus. 2. Almost all cells tested could be antidromically invaded following electrical stimulation of the contralateral red nucleus, showing that they were cerebellar efferent neurones. 3. A little over half of the interpositus neurones were spontaneously active, usually at rates of less than 20 impulses/sec. 4. About 40% of the cells had no spontaneous activity, although they gave brisk responses to electrical stimulation of cutaneous nerves. Such silent units were encountered most frequently in the earlier stages of an experiment, but a number were found more than 15 hr after the beginning of an experiment. 5. Stimulation of cutaneous and mixed nerves of the fore and hind limbs provoked impulse discharges of the cells and also produced phases of deceleration of the resting discharge of spontaneously firing cells. 6. The typical response of an interpositus neurone consisted of a short latency (6-35 msec) discharge, usually separated from a long latency (50-500 msec) discharge by a period of inhibition or return to the resting discharge rate. The two phases of excitation appeared to be independently generated, since in a number of cells one phase appeared without the other. In addition, the later phase of excitation was abolished in all cells tested by a small dose of pentobarbitone which produced very little effect on the earlier phase. The long latency response was quantitatively much greater, sometimes consisting of 50 or more impulses in a response which lasted several hundred msec, but was very variable from one trial to another. 7. The long latency discharge and sometimes the preceding inhibition could readily be mimicked by single shock stimulation of the region of the contralateral inferior olive. Short latency discharges were, however, rarely evoked by olivary stimulation. 8. It is suggested that the short latency responses of the interpositus neurones were a result of synaptic excitation via cerebellar afferents, while the ensuing inhibition was a result of post-synaptic inhibition resulting from the Purkinje cell excitation due to the afferent volleys. It is suggested that the long latency excitation is due to the afferent volleys. It is suggested that the long latency excitation is due at least in part to disinhibition resulting from long pauses in Purkinje cell firing following their activation by climbing fibre afferents. 9. The possibility that these long latency responses have a physiological significance in relation to locomotion is discussed.

Action Potentials

Discharge patterns of Purkinje cells in cats anaesthetized with alpha-chloralose.

1. Micro-electrodes have been used to record from 119 Purkinje (P) cells in the paramedian lobule of the cerebellum in cats anaesthetized with alpha-chloralose. 2. The spontaneous discharge rate and degree of irregularity of the discharge varied very much from one cell to another; the over-all mean rate (about 25/sec) was a little lower than has been reported either for barbiturate anaesthetized or for decerebrate unanaesthetized preparations. 3. Following electrical stimulation of a peripheral nerve, most P cells responded with both simple spikes and a climbing fibre response. This initial response was usually succeeded by a prolonged period of silence (over-all mean duration 350 msec) before resumption of the tonic simple spike discharge. Similar response-silence sequences could also be evoked by mechanical stimulation such as a tap applied to the pads of the forepaw. 4. Electrical stimulation of the inferior olive evoked climbing fibre responses followed by a prolonged pause in the simple spike discharge of the cell. 5. In six individual preparations, recordings were made both from P cells of the paramedian lobule and from neurones of nucleus interpositus (to which the former project). Comparison of the responses of the two types of neurone to peripheral nerve and inferior olivary stimulation showed that the end of the pauses in P cell firing correlated well with the end of a prolonged period of facilitation of the interpositus neurones. 6. These results support the hypothesis advanced in an earlier report (Armstrong, Cogdell & Harvey, 1975) that the prolonged facilitatory responses of interpositus neurones are essentially disinhibitory responses resulting from reduction in the activity of overlying cells, and that responses of P cells and of interpositus neurones consist, in general, of modulations of activity which are mutually out of phase.

Action Potentials

Effects of pentazocine on coronary hemodynamics under pentobarbital or chloralose-urethane anesthesia in dogs.

The effect of pentazocine on the coronary hemodynamics was studied in anesthetized dogs. Under pentobarbital anesthesia pentazocine did not cause any significant changes in the coronary hemodynamics. Under chloralose-urethane anesthesia, however, it produced a statistically significant increase in heart rate, left coronary blood flow rate, myocardial oxygen consumption as well as myocardial oxygen extraction rate, but a decrease in coronary vascular resistance. These results indicate that the effects of pentazocine on the coronary hemodynamics are modified significantly by the drugs used for basal anesthesia.

Anesthesia, Intravenous

The response of three strains of fowl to alpha-chloralose.

A heavy and two light strains of pullets suffered a decline in egg production but an improvement in body weight gains when alpha-chloralose, a tranquilizer, was included in their diets at .1 to .3%. Feed efficiency also experienced a decline while egg size and Haugh unit were not affected.

Animals