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Cerebral blood flow and cerebrovascular reactivity after inhibition of nitric oxide synthesis in conscious goats.

1. The role of nitric oxide in the cerebral circulation under basal conditions and after vasodilator stimulation was studied in instrumented, conscious goats, by examining the action of inhibiting endogenous nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME). 2. In 6 unanaesthetized goats, blood flow to one brain hemisphere (electromagnetically measured), systemic arterial blood pressure and heart rate were continuously recorded. L-NAME (35 mg kg-1 by i.v. bolus) decreased resting cerebral blood flow by 43 +/- 3%, increased mean arterial pressure by 21 +/- 2%, and decreased heart rate by 41 +/- 2%; cerebrovascular resistance increased by 114 +/- 13% (P < 0.01); the immediate addition of i.v. infusion of L-NAME (0.15-0.20 mg kg-1 during 60-80 min) did not significantly modify these effects. Cerebral blood flow recovered at 72 h, arterial pressure and cerebrovascular resistance at 48 h, and heart rate at 6 days after L-NAME treatment. 3. A second treatment with L-NAME scheduled as above reproduced the immediate haemodynamic effects of the first treatment, which (except bradycardia) reversed with L-arginine (200-300 mg kg-1 by i.v. bolus). 4. Acetylcholine (0.01-0.3 micrograms), sodium nitroprusside (3-100 micrograms) and diazoxide (0.3-9 mg), injected into the cerebral circulation of 5 conscious goats, produced dose-dependent increases in cerebral blood flow, and decreases in cerebrovascular resistance; sodium nitroprusside (30 and 100 micrograms) also caused hypotension and tachycardia. 5. The reduction in cerebrovascular resistance from resting levels (in absolute values) to lower doses,but not to the highest dose, of acetylcholine was diminished, to sodium nitroprusside was increased, and to diazoxide was unaffected after L-NAME, compared to control conditions. The effects on cerebrovascular resistance to acetycholine normalized within 24 h and to sodium nitroprusside within 48 h after L-NAME treatment.6. This study provides information about the evolution of the changes in cerebral blood flow and cerebrovascular reactivity after inhibition of endogenous nitric oxide in conscious animals. The results suggest: (a) endogenous nitric oxide is involved in regulation of the cerebral circulation by producing a resting vasodilator tone, (b) the cerebral vasodilatation to acetylcholine is mediated, at least in part, by nitric oxide release, and (c) inhibition of nitric oxide production induces supersensitivity of cerebral vasculature to nitrovasodilators.

Acetylcholine↗

Cardiovascular actions of dopexamine in anaesthetized and conscious dogs.

1. Arterial blood pressure, heart rate and cardiac contractility were measured in pentobarbitone-anaesthetized mongrel dogs and in conscious, instrumented dogs. 2. In anaesthetized dogs (n = 5), dose-response curves were obtained by intravenous infusion of increasing doses of dopexamine (5-20 micrograms kg-1 min-1). Infusions were administered three times to each animal to determine whether the responses were reproducible. Dopexamine increased heart rate and myocardial contractility and decreased blood pressure. The dose-response curves for dopexamine did not differ significantly over time. 3. In a second group of dogs (n = 6), dose-response curves (5-20 mg kg-1 min-1) were obtained as above and repeated after the administration of amitriptyline (2 mg kg-1, i.v.). Amitriptyline caused a non-significant reduction in the inotropic and chronotropic responses to dopexamine. 4. Control dose-response curves for dopexamine (5-50 micrograms kg-1 min-1) were similarly obtained in a third group of dogs (n = 6), and repeated after bilateral vagotomy and sympathetic denervation of the heart. In these animals, a third dose-response curve for dopexamine was obtained after the administration of ICI 118551 (0.2 mg kg-1, followed by 0.2 mg kg-1 h-1). The chronotropic response to dopexamine was significantly reduced after cardiac denervation. There was a small, non-significant reduction in the inotropic and depressor responses after denervation. Administration of ICI 115881 significantly reduced both the inotropic and chronotropic response to dopexamine and caused a non-significant reduction in the depressor response. 5. The effect of raclopride (0.2 mumol kg-1, p.o.) was investigated by comparison of the dose-response curves for dopexamine in a control group of dogs (n = 6) to those obtained in dogs which had been pretreated with raclopride (n = 5). Raclopride had no significant effect on the cardiovascular responses to dopexamine. 6. In conscious, instrumented dogs (n = 5), pretreated with raclopride, dose-related positive inotropic and chronotropic and depressor responses to dopexamine infusions were recorded. The chronotropic responses in conscious animals were significantly greater than those in the anaesthetized animals.7. The results of this study indicate that both the positive inotropic and chronotropic actions of dopamine are due to a combination of direct, Beta2-adrenoceptor-mediated effects and the baroreceptor reflex response to the depressor action of the drug.

Adrenergic beta-Antagonists↗

Comparisons of the effects of nicorandil, pinacidil, nicardipine and nitroglycerin on coronary vessels in the conscious dog: role of the endothelium.

1. The vasodilator properties of nicorandil on large and small coronary arteries were compared to those of nicardipine, pinacidil, nitroglycerin and acetylcholine in six conscious dogs. 2. Intravenous bolus injections of acetylcholine (0.1 micrograms kg-1), nitroglycerin (0.3-3 micrograms kg-1), pinacidil (10-100 micrograms kg-1), nicardipine (3-30 micrograms kg-1) and nicorandil (10-100 micrograms kg-1) dose-dependently increased circumflex coronary artery diameter and decreased coronary vascular resistance, indicating vasodilator effects on both conduit and resistance coronary arteries. 3. Three days after removal of the endothelium of the circumflex coronary artery (balloon angioplasty), pinacidil- and nicardipine-induced dilation of large coronary arteries was greatly reduced (both -76%, P < 0.01) whereas that produced by nitroglycerin and nicorandil was decreased only slightly and to a similar extent for both drugs (-19%, P < 0.01 and -28%, P < 0.05, respectively). 4. Thus in conscious dogs, nicardipine- and pinacidil-induced dilatation of large coronary arteries is endothelium-dependent. In contrast, the vasodilator effects of nitroglycerin and nicorandil on conduit vessels are endothelium-independent. 5. Finally, our results demonstrate that nicorandil dilates the large coronary arteries through its nitrate-like action and that the ATP-potassium channel opening properties of the drug are not involved in this effect in the conscious dog.

Acetylcholine↗

Study of SR 142801, a new potent non-peptide NK3 receptor antagonist on cardiovascular responses in conscious guinea-pig.

1. The cardiovascular responses to intravenous (i.v.) injection of natural tachykinins, substance P (SP), neurokinin A (NKA), neurokinin B (NKB) and selective tachykinin (NK) receptor agonists, [Sar9, Met(O2)11]SP, [beta Ala8]NKA(4-10), [MePhe7]NKB and senktide were assessed in conscious, freely moving, guinea-pigs. 2. SP and [Sar9, Met(O2)11]SP (1-1000 pmol kg-1) induced dose-dependent decreases in mean arterial blood pressure (MAP) accompanied by increases in heart rate (HR). NKA evoked only weak hypotensive effects at high doses (3000 pmol kg-1) whereas [beta Ala8]NKA(4-10) (1-3000 pmol kg-1) had no effects. By contrast, NKB [MePhe7]NKB (1-10,000 pmol kg-1) and senktide (1-1000 pmol kg-1), produced dose-related hypertensive effects with the following rank order of potency: senktide > [MePhe7]NKB > NKB. Bradycardia occurred simultaneously with the increases in arterial pressure. 3. The pressor response to intravenous injection of senktide (300 pmol kg-1) was partially reduced by pretreatment with prazosin (0.71 mumol kg-1), or clonidine (0.38 mumol kg-1) and was completely inhibited by the combination of the two compounds. Atropine (1.5 mumol kg-1) suppressed the decrease in HR induced by senktide without altering the blood pressure response. These findings suggest that the blood pressure response to senktide is an indirect effect mediated by noradrenaline released from sympathetic nerve endings, whereas the bradycardia is of vagal reflex origin. 4. SR 142801, ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl) propyl)-4-phenyl-piperidin-4-yl)-N-methylacetamide), a potent and specific non-peptide NK3 receptor antagonist dose-dependently (0.46-4.6 mumol kg-1, i.v.; 4.6-46 mumol kg-1, p.o.) inhibited the cardiovascular effects of senktide and displayed a long-lasting inhibitory effect after oral administration. By contrast, SR 142806 (4.6 mumol kg-1, i.v.), the (R)-enantiomer of SR 142801 had no effect on the responses to senktide. SR 142801 at a high dose (15 mumol kg-1, i.v.) was inactive toward the [Sar9, Met(O2)11]SP-induced hypotension. 5. SR 142801 did not modify MAP in conscious guinea-pigs both after i.v. (4.6 and 15 mumol kg-1) and oral (46 and 150 mumol kg-1) administration, showing a lack of agonistic properties. However, a slight reduction in HR was observed only after i.v. injection. 6. In conclusion, these results show evident differences in the functional role of tachykinin receptors in the peripheral control of the cardiovascular system. Furthermore, a clear pressor effect of senktide, which was selectively blocked by SR 142801, was observed in conscious guinea-pigs. Hence, this antagonist appears suitable for investigating the functional role of NK3 receptors.

Analysis of Variance↗

Conscious sedation with intermittent midazolam and fentanyl in electrophysiology procedures.

OBJECTIVES: To determine the safety and efficacy of intermittent midazolam and fentanyl conscious sedation for electrophysiology procedures (EP). BACKGROUND: Intermittent midazolam and fentanyl conscious sedation was administered in 700 consecutive cases (175 radiofrequency ablations, 163 EP studies, 261 pacemakers, and 101 implantable cardioverter-defibrillators) for 471 patients (239 males, 51%) mean age 65 +/- 15 years. The mean dose of midazolam was 0.063 mg/kg/hr and fentanyl was 0.591 microgram/kg/hr. METHODS: Cardiac rate and rhythm were monitored continuously, while blood pressure and arterial oxygen saturation were noninvasively assessed every 5 minutes. Drugs were administered in aliquots of 0.5 to 2.0 mg of midazolam and 6.25 to 25 micrograms of fentanyl as determined by clinical condition every 15 to 30 minutes. RESULTS: There were no deaths. In no case was endotracheal intubation required. Mild hypoxemia (SaO2 > 80%, but < 90%) occurred in 17 cases (2.4%) and was easily reversed with verbal stimulation and oropharyngeal repositioning (12 cases, 1.7%), increased F1O2 (3 cases, 0.4%), or intravenous naloxone (2 cases, 0.3%). Reversible hypotension (systolic blood pressure < 90, but > 60 mmHg) occurred in 14 patients (2.0%) and was corrected with intravenous crystalloid bolus or flumazenil (10 cases, 1.4%) or inotrope infusion (4 cases, 0.6%). No patient stay was prolonged due to sedation. Only five patients (0.7%) had any recollection of the procedure, while two (0.3%) were aware of pain. All hypoxemic episodes occurred during the first hour, whereas 43% (6/14) of hypotensive episodes occurred after the first hour. CONCLUSION: Conscious sedation with intermittent midazolam and fentanyl is safe and efficacious for a broad range of EP procedures.

Aged↗

Hypertension-induced protein leakage in the brain in ethanol-intoxicated conscious and anesthetized rats.

Ethanol has been shown to aggravate the blood-brain barrier (BBB) dysfunction in cerebral trauma and in cerebral gas embolism, possibly by changing the endothelial cell membrane. No difference in protein extravasation was found between intoxicated and control rats under nitrous oxide anesthesia after the injection of bicuculline, a drug that hemodynamically gives rise to high blood pressure in combination with cerebral vasodilatation. In contrast there was a statistically significant increase in protein leakage in conscious intoxicated rats. The fact that ethanol increased the vulnerability only in conscious rats might indicate that nitrous oxide and ethanol have a common effect on the endothelial cell membranes or that nitrous oxide neutralizes an action of ethanol. Protein leakage induced by acute hypertension is more severe in rats anesthetized with nitrous oxide than in conscious rats, a difference that might to some extent be related to an effect of nitrous oxide on the endothelial cells. Further studies are needed to evaluate the influence of ethanol and nitrous oxide on the endothelial cell membrane.

Alcoholic Intoxication↗

Disease consciousness and coping strategies of patients with schizophrenic psychosis.

In 50 schizophrenic patients, semistructured interviews were carried out concerning disease consciousness, occupation with the disease and behaviour and coping in case of psychotic experiences; 72% of the patients occupied themselves with their disease. In 84% a disease consciousness was present; 38% gave a multifactorial explanation for their psychosis. In 94% the occasional appearance of psychotic experiences was acknowledged. In 86% specific changes of the individual behaviour for coping with these experiences were described. These changes included withdrawal, increasing of interpersonal contact, cognitive control, symptomatic behaviour and adjustment of the neuroleptic medication. The study shows that schizophrenic patients are not passive victims of their disease. In the majority of cases a disease consciousness is present. The patients try to cope with their psychotic experiences in individually different ways. It is assumed that a better knowledge of these strategies might enable the clinician to use these phenomena as an adjunct to pharmacotherapy.

Adaptation, Psychological↗

Time course of changes in plasma renin after blockade of the renin-system. Studies of conscious and anaesthetized, normal, adrenalectomized and spontaneously hypertensive rats.

Inhibition of the angiotensin I converting enzyme with SQ 20.881 results in a 2 to 35 fold increase in plasma renin concentration in normal rats and in spontaneously hypertensive rats. The effect is transient, lasting for 1 to 3 hours even in the presence of prolonged blockade. The relative increase is independent of the pretreatment plasma renin concentration. The blood pressure is unchanged in conscious rats in which the effect of SQ 20.881 on plasma renin is believed to be due to a blockade of the negative feedback of angiotensin II on renin release. In anaesthetized rats, SQ 20.88) has an additional hypotensive effect which augments the increase in plasma renin. Saralasin is without effect on blood pressure and plasma renin in conscious normal rats and in spontaneously hypertensive rats, while it causes a transient 3 to 27 fold increase in plasma renin concentration in anaesthetized rats. It is suggested that this increase is hardly due to an interception of the feedback, but to the concomitant fall in blood pressure, as a similar hypotension and increase in plasma renin is produced by dihydralazine. It is furthermore found that Saralasin blocks renin release induced by SQ 20.881. This demonstrates that Saralasin is bound to the receptors in the juxtaglomerular cells and has slight, agonistic properties there. Both in conscious rats and in anaesthetized adrenalectomized rats substituted with DOCA and salt, SQ 20.881 as well Saralasin causes transient increases in plasma renin concentration. If such rats are only substituted with salt and not with DOCA, the effects of both blockers are in the form of severe hypotension and a permanent elevation of plasma renin.

Adrenalectomy↗

Distension of pulmonary vein--left atrial junction: heart rate responses in conscious and anesthetized dogs.

The cardiac chronotropic effects of distension of pulmonary vein-left atrial junction were investigated in conscious dogs and in dogs anesthetized with intravenous alpha-chloralose (100 mg/kg) or pentobarbital (30 mg/kg). All the experiments were made on trained, chronically instrumented, closed chest animals held in horizontal position. Inflation of a single small balloon in the junction elicited a tachycardic response both in conscious and chloralose-anesthetized dogs, while in pentobarbital anesthesia no change in heart rate was found. Contrary to reports of other investigators, no transient bradycardia was found, nor any correlation between predistension heart rate and the increase in heart rate due to the distension. It is suggested that the choice of anesthetic can be done only after its modifying effect on the parameter studied is known. Only the use of trained, chronically instrumented and conscious dogs will reveal this effect.

Animals↗

Push-pull perfusion of the hypothalamus and the caudate nucleus in conscious, unrestrained animals.

The present results further confirm the usefulness of the push-pull cannula to study the in vivo activity of several neural systems in conscious, freely moving animals. However, it is evident that the inflammatory reaction to the local injury induced by the cannula may have different consequences in the function of a particular brain area. In the caudate nucleus, the responsiveness of the dopaminergic terminals of the nigrostriatal DA system to local infusion of AMPH was clearly reduced after the first two to three weeks post cannula implant. In contrast, in the hypothalamus of the rat and the rabbit, the spontaneous fluctuating activity of the LHRH pulse generator remained unaffected during a two to three month period when several perfusions could be performed in the same animal. Further studies will be required to establish the reasons for such marked differences in response to injury of these two brain structures. Various neurochemicals can be measured simultaneously from the hypothalamus of conscious rabbits. The present results indicate that NE hypothalamic impulse flow increases during the afternoon whereas the impulse flow of DA (as estimated by DOPAC output) decreases or does not change. In rabbit No. 2, simultaneous measurement of hypothalamic NE release and LHRH release indicates an absence of correlation. In sharp contrast, the simultaneous measurement of prostaglandin E2 release and LHRH release from the hypothalamus of rabbit 2-ER revealed a closer association between these two neuronal events. Apparently the push-pull technique can be used to examine long-term seasonal as well as circadian (extended 24 hr perfusion) spontaneous changes in the activity of the LHRH pulse generator in individual animals. It seems that seasonal changes characterize the function of the rabbit LHRH pulse generator. Lastly, physiological doses of progesterone infused for short times directly into the hypothalamus of female rabbit stimulate the LHRH pulse generator of this species with marked increases in the amplitude of the LHRH signal. In conclusion, the PPP technique coupled to HPLC-EC and RIA procedures to measure localized release of neurotransmitters, metabolites, and neuropeptides simultaneously in the same perfusate samples from discrete brain areas appears to be a powerful technique in furthering our knowledge of the in vivo local neurochemistry of the brain of conscious, freely moving animals.

Animals↗

A suggested curriculum for teaching conscious sedation in advanced general practice programs: GPR and AEGD. American Association of Hospital Dentists.

Previously published national guidelines related to the teaching and performance of conscious sedation in dentistry have not included guidance in this area for program directors of General Practice Residency and Advanced Education in General Dentistry Programs. A suggested curriculum is presented here for use by program directors of such programs who wish to design training experiences in their own programs or as a reference for program directors who wish to compare their programs with experiences provided in other locations. Guidelines are provided for facilities, equipment, personnel, records and preparation necessary to perform conscious sedation procedures, as well as goals, objectives, and evaluation methodology for training residents in conscious sedation.

Anesthesiology↗

Self-reports of mathematics self-concept and educational outcomes: the roles of ego-dimensions and self-consciousness.

BACKGROUND: There is a need for research to (a) explore more fully the academic outcomes that follow from under-/over-rating of self-concept and (b) identify factors that predict the nature of self-reports of self-concept as well as under- and over-rating of this self-concept. AIMS: The study examines the link between students' self-appraisals of both mathematics self-concept and under-/over-rating of this self-concept and educational outcomes in mathematics such as achievement and motivation (future plans for mathematics). Ego-dimensions (ego-orientation and competence-valuation) and public self-consciousness were examined as two factors that might contribute to predicting these self-appraisals. SAMPLE: Findings are drawn from a sample of 382 male and female high school students ranging in age from 14 to 16 years. METHODS: Students responded to a questionnaire (at Time 1) that assessed self-concept, motivation orientation, competence-valuation, self-consciousness, and mathematics motivation. Teachers rated each student using a brief mathematics self-concept scale. RESULTS: Higher mathematics self-concept and over-rating of this self-concept were predictive of higher levels of mathematics motivation and later mathematics achievement (Time 2). Findings also indicate that ego-orientation and competence-valuation are positively associated with mathematics self-concept and over-rating, whilst public self-consciousness negatively predicts mathematics self-concept and is also associated with a tendency to under-rate oneself in this domain.

Achievement↗

The role of the autonomic nervous system in the depression of parotid salivary secretion during hyperkalaemia in conscious sheep.

The rate of flow and electrolyte concentration of parotid saliva were measured before, during and after intravenous and contralateral intracarotid infusion of KCl (0.5 mol.1(-1)) and NaCl (0.5 mol.1(-1)) at 385-625 mumol. min(-1) for 40 min into 5 sheep. In intact conscious sheep contralateral intracarotid infusion of KCl caused marked depression of salivary secretion in all experiments whereas infusion of NaCl had no consistent effect on flow. Intravenous infusion of KCl into the intact conscious sheep caused a slight depression of salivary secretion but minimum flow was significantly higher than that during intracarotid infusion. When the sheep were anaesthetized salivary flow rates were low and contralateral intracarotid infusion of KCl either had no effect on flow or caused an increase in flow. After ipsilateral cervical sympathectomy contralateral intracarotid infusion of KCl into the conscious sheep caused a marked depression of salivary flow similar to that occurring when the sheep were intact. After section of the secretomotor nerve of the gland salivary flow rates were low and contralateral intracarotid infusion of KC1 had no effect on flow. The salivary flow responses of the sheep were consistent, regardless of whether the KCl infusions were given within 24 h or 1-2 weeks after cervical sympathectomy or secretomotor nerve section. Salivary sodium concentration was negatively correlated with salivary flow in all experiments. It was concluded that potassium acted at a site located in the head but by direct action on the salivary gland. The depression of salivary secretion by hyperkalaemia resulted from a decline in neural activity in the parasympathetic secretomotor innervation of the parotid gland.

Anesthesia, General↗

Renal excretion of sodium after bilateral renal sympathectomy in the anaesthetized and conscious rat.

1. The effect of bilateral renal denervation on sodium excretion was studied in conscious rats on normal, low and high sodium diet, and in rats recovering from anaesthesia, as well as in anaesthetized rats fed a normal sodium diet. 2. Sodium excretion of bilaterally denervated conscious rats on normal sodium intake and during either 2 weeks of sodium depletion or 6 days of sodium loading was not different from that of controls, despite changes in sodium supply of more than two orders of magnitude. Cortical noradrenaline concentration of control kidneys was 138 +/- 12 ng/g, but was only 7 +/- 3 ng/g (P less than 0 . 001) 6 weeks after denervation. 3. In rats recovering from anaesthesia urine flow, sodium excretion and glomerular filtration rate (G.F.R.) were not affected by denervation. 4. In anaesthetized non-diuretic rats on normal sodium diet chronic bilateral renal denervation increased urine flow and sodium excretion four and five times, respectively, with no changes in G.F.R. 5. Mean arterial blood pressure in bilaterally denervated anaesthetized rats and in those recovering from anaesthesia was decreased by 2 . 7 kPa, P less than 0 . 001 and 1 . 2 kPa, P less than 0 . 05, respectively. 6. The participation of renal nerves in the regulation of sodium excretion in conscious rats seems improbable. The denervation natriuresis in anaesthetized rats can be related to higher pre-denervation renal sympathetic nervous activity due to narcosis and surgical stress.

Anesthesia, General↗

Comparison of aspirin and indomethacin pre-treatments on the responses to reduced renal artery pressure in conscious dogs.

To examine the role of prostaglandins in physiologically induced renin release, we reduced renal artery pressure within the autoregulatory range in chronically instrumented conscious dogs with aspirin, indomethacin or no pre-treatment. In untreated dogs, reduction of renal artery pressure to 60 mmHg for 90 min produced rises in plasma renin activity (+ 5.4 +/- 1.0 ng ml.-1 hr-1) and mean arterial pressure (+ 17 +/- 2 mmHg) without significant effect on renal blood flow (n = 13). Aspirin pre-treatment (2 X 25-40 mg kg-1 orally) had no effect on the renin, arterial pressure or renal blood flow responses to renal artery pressure reduction (n = 7). In contrast, indomethacin pre-treatment (2 X 2-3 mg kg-1 orally) significantly lessened the increase in plasma renin activity during reduced renal artery pressure (+ 2.0 +/- 0.3 ng ml.-1 hr-1, n = 11). The relative effectiveness of aspirin and indomethacin in inhibiting prostaglandin production in the kidney was then tested in separate experiments by measuring the renal blood flow responses to renal artery injections of arachidonate (5-200 micrograms kg-1). In the doses used above, aspirin markedly attenuated the blood flow response to arachidonate but indomethacin had almost no effect. Both aspirin and indomethacin abolished the hypotensive effect of intravenous arachidonate (0.5 mg kg-1). These results tentatively suggest that indomethacin may not effectively inhibit renal prostaglandin production in conscious dogs at the doses used in these experiments. Thus the reduced renin release in response to lowered renal artery pressure in indomethacin pre-treated dogs may have been due to another, non-prostaglandin action of indomethacin. The results from the aspirin pre-treated dogs suggest that prostaglandins are not involved in the release of renin in response to reduced renal artery pressure in conscious dogs.

Animals↗

Intracoronary veratrine attenuates carotid baroreceptor reflex regulation of blood pressure in conscious dogs.

1. The effect of activation of left ventricular cardiac receptors on carotid baroreflex control of blood pressure, heart rate, cardiac output, and total peripheral resistance was determined in conscious dogs. Previous studies in conscious subjects assessed only the effect on baroreflex control of heart rate. 2. Dogs with denervated aortic baroreceptors were equipped with aortic flow probes, cardiac pacing electrodes, and catheters in the aorta, vena cava, and left circumflex coronary artery. Both carotid sinus regions were prepared for reversible vascular isolation. 3. Left ventricular receptors were stimulated by an infusion of veratrine (0.1-1.0 micrograms kg-1 min-1) into the left circumflex coronary artery. 4. Veratrine infusion decreased control blood pressure only 10 +/- 2 mmHg, but it decreased the range of baroreflex control of blood pressure by 50% and decreased maximum baroreflex gain by 42%. Both the cardiac output and total peripheral resistance components of the baroreflex were attenuated. 5. Baroreflex control of blood pressure was unaffected by intravenous veratrine or by intracoronary infusion of vehicle. 6. Intracoronary veratrine had no effect after autonomic ganglionic blockade. 7. When cardiac output was kept nearly constant (by beta-adrenergic and cholinergic receptor blockade or by beta-blockade and cardiac pacing), intracoronary veratrine still attenuated baroreflex control of blood pressure and total peripheral resistance. Veratrine impaired the ability of the baroreflex to utilize alpha-adrenergic mechanisms to control total peripheral resistance. 8. We conclude that activation of ventricular receptors attenuates baroreflex regulation of blood pressure in conscious dogs through an attenuation of baroreflex control of both cardiac output and total peripheral resistance.

Animals↗

Cardiovascular responses to static exercise in conscious cats: effects of intracerebroventricular injection of clonidine.

1. Static exercise elicits increases in arterial blood pressure and heart rate (HR) in humans and conscious animals. In this study, the effects of intracerebroventricular (I.C.V.) administration of clonidine, an alpha 2-adrenergic agonist, on these cardiovascular responses were investigated using conscious cats. Four cats were operantly trained to extend a forelimb and press a bar (200-650 g) for 15-60 s. A stainless-steel cannula was inserted into the right lateral ventricle for I.C.V. injection of drugs, and a common carotid artery was catheterized to measure mean arterial pressure (MAP) and HR. The number of exercise trials and changes in MAP, HR and force were pooled for 30 min periods. After the cats exercised for 30 min, either artificial cerebrospinal fluid (CSF) or clonidine (2 or 5 micrograms) were administered intracerebroventricularly. 2. Before clonidine injection, fifty-two exercise trials increased MAP and HR by 15 +/- 3 mmHg and 41 +/- 5 beats min-1, respectively. Administration of clonidine (2 micrograms) did not alter the resting MAP and HR, but attenuated the increases in MAP and HR in response to exercise (0-30 min post-clonidine: n = 81; delta MAP, 6 +/- 3 mmHg; delta HR, 20 +/- 6 beats min-1; 30-60 min post-clonidine: n = 71; delta MAP, 4 +/- 4 mmHg; delta HR, 17 +/- 8 beats min-1). Administration of artificial CSF I.C.V. had no effect on the cardiovascular responses to static exercise. 3. An increased dose of clonidine (5 micrograms) decreased resting MAP and HR by 31 +/- 7 mmHg and 37 +/- 7 beats min-1, respectively, and markedly blunted the cardiovascular responses to exercise (pre-clonidine: n = 52; delta MAP, 17 +/- 3 mmHg; delta HR, 38 +/- 5 beats min-1; post-clonidine 0-30 min: n = 66; delta MAP, 4 +/- 2 mmHg; delta HR, 15 +/- 5 beats min-1; post-clonidine 30-60 min: n = 60; delta MAP, 4 +/- 2 mmHg; delta HR, 14 +/- 6 beats min-1). Pretreatment with the alpha 2-adrenergic antagonist, yohimbine (8 micrograms, I.C.V.), blocked the attenuating effects of I.C.V. administration of clonidine (5 micrograms). 4. These results show that stimulation of central alpha 2-adrenoceptors by clonidine attenuates the cardiovascular responses to static exercise in conscious cats. In addition, this study suggests that alpha 2-adrenoceptors blocked by yohimbine injected I.C.V. do not appear to have a tonic influence on HR and blood pressure.

Animals↗

Invasive procedures carried out in conscious children: contrast between North American and European paediatric oncology centres.

AIM: To define practice in managing repeated invasive procedures in selected paediatric oncology centres in North America and Europe, especially the United Kingdom; to define and contrast concerns that shape policy making, and to contrast practice, particularly regarding procedures performed on conscious patients. METHODS: Postal survey: 118 centres of the Pediatric Oncology Group and the United Kingdom Children's Cancer Study Group received questionnaires. RESULTS: 68 questionnaires (58%) were returned (52 from North America, 12 from Europe). For all procedures, North American centres tended to use less effective techniques than European, especially for bone marrow procedures. Many North American centres reported performing these on conscious patients on at least three quarters (25%) or half (30%) the occasions. In contrast, corresponding figures for the European centres were 6% and 0%. CONCLUSIONS: Many bone marrow procedures are still carried out in the conscious patient despite the safety and effectiveness of modern anaesthetic and deep sedation techniques. There appears to be a greater reluctance to offer these to patients in North American centres than in European ones. This may reflect a misperception that the risks of adverse effects are high. Several non-pharmacological techniques are used, but they remain uncommon.

Anesthesia, General↗