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The relationship between life satisfaction, self-consciousness, and the Myers-Briggs type inventory dimensions.

The study was an investigation of the relationship between psychological well-being, life satisfaction, self-consciousness, and the four Myers-Briggs Type Indicator dimensions (MBTI; I. B. Myers & M. H. McCaulley, 1985). The participants were 97 college students (79 women and 18 men whose mean age was 31.4 years). All the students were administered four instruments, the Psychological Well-Being Inventory (C. D. Ryff, 1989), the Satisfaction With Life Scale (E. Diener, R. A. Emmons, R. J. Larsen, & S. Griffin, 1985), the Self-Consciousness Scale-Revised (M. F. Scheier & C. S. Carver, 1985), and the MBTI (Form G Self-Scoring). MANOVAs revealed significant differences on three of the four dimensions of the MBTI with extraverts showing higher psychological well-being and life satisfaction and lower self-consciousness than introverts. Intuition types scored higher in psychological well-being and lower in self-consciousness than Sensing types. Judging types scored higher in psychological well-being than Perceiving types. Correlational analyses showed that most dimensions of psychological well-being were negatively related to self-consciousness. The relationship between life satisfaction and personality variables is discussed.

Adult↗

Recovered consciousness: a hypothesis concerning modularity and episodic memory.

Why should conscious recollection be associated with recovery of some memories and not others? A hypothesis is proposed and defended that the medial temporal lobe/hippocampal complex (MTL/H) and related limbic structures comprise a memory module that receives as its input only information that is consciously apprehended. The module then binds or conjoins into memory traces those neural elements that mediated the conscious experience so that effectively "consciousness" is as intergral a part of the memory traces as it was during the experience of the event. When memory traces are retrieved, what is recovered are the phenomenological records (Conway, 1992) of experienced events which are integrated content-consciousness packets. Evidence is presented which suggests that the MTL/H module satisfies Fodorian criteria of modularity. The MTL/H module is compared to perceptual modules in nonfrontal neocortex that mediate performance on tests of memory without awareness and to prefrontal neocortex that acts as a central working-with-memory system that operates on the input to MTL/H and the shallow output from it.

Animals↗

A randomized, double blind, placebo-controlled study to investigate the use of conscious sedation in conjunction with paracervical block for reducing pain in termination of first trimester pregnancy by suction evacuation.

BACKGROUND: This study evaluated the role of conscious sedation in pain relief during termination of first trimester pregnancy by suction evacuation (SE) under local anaesthesia. METHODS: A hundred women undergoing SE before 12 weeks gestation were randomized by computer using the sealed envelope method to receive placebo (saline) or conscious sedation (2 mg midazolam and 25 microg fentanyl) i.v. 5 min before cervical dilatation. Paracervical block was given to all patients, 2 min later. Pain scores during and after SE, post-operative side-effects and satisfaction level were compared. RESULTS: No statistically significant differences in pain scores were found between the two groups. Post-operative side-effects such as dizziness (P = 0.015) and drowsiness (P < 0.001) were significantly more severe in the conscious sedation group. However, patients in the conscious sedation group reported better satisfaction levels than the control group (P = 0.003). CONCLUSION: The use of conscious sedation significantly improved patient satisfaction during termination of first trimester pregnancy by SE under local anaesthesia, despite a lack of improvement in pain relief and the presence of increased severe dizziness/drowsiness in the post-operative period.

Abortion, Induced↗

Patient-controlled versus anesthesiologist-controlled conscious sedation with propofol for dental treatment in anxious patients.

UNLABELLED: In a randomized, cross-over study, we prospectively compared the efficacy and quality of two methods to achieve conscious sedation with propofol in 11 unpremedicated, anxious dental patients. Each patient underwent two dental procedures, one that was conducted under target-controlled infusion (TCI) by the anesthesiologist (ACS), and the other that used patient-controlled sedation (PCS). The initial target concentration in the ACS mode was 2.5 microg/mL, which was manipulated in both directions until the desired clinical end point was achieved. In the PCS mode, a 4-mg bolus of propofol (10 mg/mL) was delivered at each activation of the machine, infused over 7 s without a lockout interval. The anxious dental patients could induce and maintain conscious sedation with the PCS settings. The mean (range) venous blood propofol concentrations were not significantly different with either mode: ACS 1.8 (0.8-2.7) microg/mL and PCS 1.2 (0.2-2.5) microg/mL. The level of patient satisfaction, quality of sedation, and treatability were not different for either mode of sedation. The intensity of amnesia for intraoperative events was related to the blood concentrations achieved. In the ACS mode, one patient became unresponsive (sedation level 4) immediately after the start of sedation. No adverse cardiorespiratory effects resulted from either mode of propofol sedation. Five patients expressed a strong preference for PCS, and three would prefer ACS in the future. The results of the present study suggest that with these PCS settings, a satisfactory level of conscious sedation and a high level of patient satisfaction was achieved. IMPLICATIONS: In a randomized, cross-over study, the blood propofol concentrations necessary to achieve conscious sedation in anxious dental patients using a target-controlled infusion conducted by the anesthesiologist versus patient-controlled sedation were not different. With the patient-controlled sedation settings, a satisfactory level of conscious sedation and a high level of patient satisfaction were achieved.

Adult↗

The interaction between propofol and clonidine for loss of consciousness.

UNLABELLED: Clonidine premedication reduces the intraoperative requirement for opioids and volatile anesthetics. Clonidine also reduces the induction dose of IV anesthetics. There is no information, however, regarding the effect of oral clonidine premedication on the propofol blood concentrations required for loss of consciousness, and the interaction between propofol and clonidine. We randomly administered target effect-site concentrations of propofol ranging from 0.5 to 5. 0 microg/mL by using computer-assisted target-controlled infusion to 3 groups of healthy male patients: Control (n = 35), 2.5 microg/kg Clonidine (n = 36), and 5.0 microg/kg Clonidine (n = 36) groups. Nothing was administered to the Control group. Clonidine (2.5 or 5.0 microg/kg) was administered orally 90 min before the induction of anesthesia in the Clonidine groups. After equilibration between the blood and effect-site for 15 min, a verbal command to open their eyes was given two times to the patients. Arterial blood samples for analysis of the serum propofol and clonidine concentrations were taken immediately before verbal commands were given. Measured serum propofol concentrations in equilibrium with the effect-site at which 50% of the patients did not respond to verbal commands (EC50 for loss of consciousness) were determined by logistic regression. The EC50 +/- SE values in the Control, 2.5 microg/kg Clonidine, and 5.0 microg/kg Clonidine groups were 2.67 +/- 0.18, 1.31 +/- 0.12, and 0.91 +/- 0.13 microg/mL, respectively. The EC50 in the 2.5 and 5.0 microg/kg clonidine groups was significantly smaller than that in the Control group (P < 0.001). The use of a response surface modeling analysis indicated that there was an additive interaction between measured arterial propofol and clonidine concentrations in relation to loss of consciousness. These results indicate that propofol and clonidine act additively for loss of consciousness. IMPLICATIONS: Oral clonidine 2.5 and 5.0 microg/kg premedication decreases the propofol concentration required for loss of consciousness.

Administration, Oral↗

Pulmonary vasodilator response to adenosine triphosphate-sensitive potassium channel activation is attenuated during desflurane but preserved during sevoflurane anesthesia compared with the conscious state.

BACKGROUND: The objective of this study was to investigate the effects of sevoflurane and desflurane anesthesia on the pulmonary vasodilator response to the adenosine triphosphate-sensitive potassium channel agonist, lemakalim, compared with the response measured in the conscious state. In addition, the authors assessed the extent to which sympathetic alpha1-adrenoreceptor inhibition and cyclooxygenase pathway inhibition modulate the vasodilator response to lemakalim. METHODS: Twenty-four conditioned male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow relationship. After preconstriction with the thromboxane analogue, U46619, dose-response relationships to lemakalim were assessed on separate days in the conscious state and during sevoflurane (approximately 3.5% end-tidal) and desflurane (approximately 10.5% end-tidal) anesthesia (approximately 1.5 minimum alveolar concentration for each anesthetic agent). The effects of sympathetic alpha1-adrenoreceptor inhibition (prazosin) and cyclooxygenase inhibition (indomethacin) on the pulmonary vasodilator response to lemakalim also were assessed in the conscious and desflurane-anesthetized states. RESULTS: Neither sevoflurane nor desflurane had a net effect on the baseline left pulmonary vascular pressure-flow relationship compared with the conscious state. The magnitude of the pulmonary vasodilator response to lemakalim was preserved during sevoflurane anesthesia but was attenuated (P < 0.05) during desflurane anesthesia compared with the conscious state. The attenuated lemakalim-induced vasodilator response during desflurane anesthesia was partially reversed (P < 0.05) by pretreatment with prazosin but not indomethacin. CONCLUSION: These results indicate that adenosine triphosphate-sensitive potassium channel-mediated pulmonary vasodilation is preserved during sevoflurane anesthesia but is attenuated during desflurane anesthesia. The attenuated response to adenosine triphosphate-sensitive potassium channel activation during desflurane anesthesia is partially mediated by reflex sympathetic alpha1-adrenoreceptor vasoconstriction.

Adenosine Triphosphate↗

Renal and depressor effects of SQ 29,072, a neutral endopeptidase inhibitor, in conscious hypertensive rats.

The depressor and renal responses to the neutral endopeptidase (NEP) inhibitor, SQ 29,072, were characterized in both the conscious spontaneously hypertensive rat (SHR) and the conscious deoxycorticosterone acetate (DOCA)/salt hypertensive rat. Inhibition of tissue NEP activity by pharmacologically active doses was also ascertained in both hypertensive models. Intravenous administration of 300 mumol/kg of SQ 29,072 significantly reduced mean arterial pressure (MAP), produced modest natriuretic and diuretic responses, and inhibited renal NEP activity by approximately 40% in conscious SHR. Doses of 100 and 300 mumol/kg of SQ 29,072 elicited greater depressor responses (-36 +/- 7 and -41 +/- 8 mm Hg, respectively) in DOCA/salt hypertensive rats than in SHR (-11 +/- 24 and -31 +/- 5 mm Hg, respectively). SQ 29,072 (300 mumol/kg, i.v.) also inhibited renal NEP activity to a greater extent (70%) in DOCA/salt hypertensive rats. Similarly, the depressor responses to exogenous ANP 99-126 (1, 3, and 10 nmol/kg, i.v.) were greater in DOCA/salt hypertensive rats (-16 +/- 4, -38 +/- 6, and -73 +/- 6 mm Hg, respectively) than in the SHR (0 +/- 6, -17 +/- 3, and -24 +/- 3 mm Hg, respectively). Finally, equidepressor doses of SQ 29,072 and ANP 99-126 both increased urine volume as well as sodium and cyclic GMP excretion in conscious DOCA/salt hypertensive rats. In conclusion, the profile of depressor and renal activities produced by SQ 29,072 was consistent with potentiation of endogenous ANP by inhibition of NEP in conscious SHR and DOCA/salt hypertensive rats.

Amino Acids↗

The use of conscious sedation for pain control during forearm fracture reduction in children: does race matter?

Recent reports in the medical literature indicate that certain racial disparities have been identified in healthcare. The authors sought to identify the potential relationship between the use of pain medications in African-American and Caucasian children undergoing forearm fracture reduction. This retrospective cohort study was performed at a university-affiliated tertiary care children's hospital emergency department. All Caucasian and African-American patients who underwent a closed reduction of a fractured ulna or radius over the 2-year observational period were enrolled. Patients were excluded from the study if they were admitted to the hospital for an open reduction or had multiple injuries. The relationship between race, gender, insurance status, time of admission, length of stay in the emergency department, fracture characteristics, and the use of conscious sedation was analyzed. t tests, chi-square tests, and stepwise logistic regression were used for data analysis. A total of 503 patients were included, 83% Caucasian and 17% African-American. Four hundred four patients received conscious sedation as part of their fracture reduction procedure and 99 did not. Univariate analysis showed that African-American and Caucasian children had different forearm fracture patterns (P = 0.0116) and different severities of angulation (P = 0.0094). Multivariate statistical analysis revealed that higher amounts of fracture translation (P < 0.0001) and angulation (P < 0.0027) and younger age of the patient (P = 0.0059) were significant predictors of conscious sedation use. Race was not found to be significantly associated with the use of conscious sedation (P = 0.0606 in univariate analysis, P = 0.1678 in multivariate analysis). The authors found that the decision to use conscious sedation for pediatric forearm fractures was not influenced by race, but was influenced by certain fracture characteristics and patient age.

Adolescent↗

Loss of consciousness: when to perform computed tomography?

OBJECTIVE: To determine the diagnostic value of physical examination (including neurologic exam) for positive computed tomography scan findings in children with closed head injury, Glasgow Coma Scale score 13-15 in the emergency department, and loss of consciousness or amnesia. DESIGN: Prospective descriptive study. SETTING: A large, tertiary, pediatric trauma center in San Diego County. PATIENTS: Children ages 2-16 with an isolated closed head injury, history of loss of consciousness or amnesia, and Glasgow Coma Scale 13-15 who were referred for pediatric trauma evaluation and received a head computed tomography as part of this evaluation. INTERVENTIONS: A standardized physical examination including skull/scalp exam, pupils, tympanic membrane, and brief neurologic exam was documented on each patient. MEASUREMENTS AND MAIN RESULTS: Subjects age 2-16 being evaluated by the pediatric trauma team for closed head injury with loss of consciousness or amnesia and Glasgow Coma Scale 13-15 received a standardized physical exam, noncontrast head computed tomography scan, and follow-up telephone call at 4-6 wks. Outcome variables include intracranial injury visualized on computed tomography scan and need for neurosurgical intervention. Ninety-eight subjects were enrolled in the study over a 1-yr period. Computed tomography scans revealed evidence of intracranial injury in 13 of 98 subjects (13%). Normal examination increased the probability of a normal computed tomography scan from.87 pretest to.90 posttest. Four of 38 subjects with normal examination were noted to have evidence of intracranial injury on computed tomography. These four subjects did not require neurosurgical intervention. Two of 98 subjects underwent neurosurgical procedures. One intracranial pressure monitor was placed for decreasing level of consciousness. One subject underwent surgical elevation of a depressed skull fracture. CONCLUSIONS: Detailed clinical examination is of no diagnostic value in detecting intracranial injuries found on head computed tomography scan. Patients with observed loss of consciousness or amnesia and Glasgow Coma Scale 13-15 should have a head computed tomography scan as part of their evaluation to avoid missing an intracranial injury.

Adolescent↗

How should functional imaging of patients with disorders of consciousness contribute to their clinical rehabilitation needs?

PURPOSE OF REVIEW: We discuss the problems of evidence-based neurorehabilitation in disorders of consciousness, and recent functional neuroimaging data obtained in the vegetative state and minimally conscious state. RECENT FINDINGS: Published data are insufficient to make recommendations for or against any of the neurorehabilitative treatments in vegetative state and minimally conscious state patients. Electrophysiological and functional imaging studies have been shown to be useful in measuring residual brain function in noncommunicative brain-damaged patients. Despite the fact that such studies could in principle allow an objective quantification of the putative cerebral effect of rehabilitative treatment in the vegetative state and minimally conscious state, they have so far not been used in this context. SUMMARY: Without controlled studies and careful patient selection criteria it will not be possible to evaluate the potential of therapeutic interventions in disorders of consciousness. There also is a need to elucidate the neurophysiological effects of such treatments. Integration of multimodal neuroimaging techniques should eventually improve our ability to disentangle differences in outcome on the basis of underlying mechanisms and better guide our therapeutic options in the challenging patient populations encountered following severe acute brain damage.

Brain↗

Effects on blood pressure of noradrenaline and isoprenaline administered into the third ventricle of the brain of anaesthetized and conscious cats.

1 Noradrenaline administered into the third ventricle of the brain (IIIv) of both conscious and anaesthetized cats induced increases in blood pressure accompanied by small and variable heart rate effects. The pressor responses were reduced after autonomic ganglion blockade indicating their likely central origin. 2 Noradrenaline when administered either into a lateral cerebral ventricle (i.c.v.) in conscious and anaesthetized cats or into the cisterna magna (i.c.) in anaesthetized cats induced falls in blood pressure accompanied by bradycardia. 3 Pressor responses to IIIv noradrenaline in conscious cats were partly blocked by either propranolol or thymoxamine indicating a possible involvement in the responses of excitatory adrenoreceptors of both alpha and beta types. 4 Pressor responses induced by IIIv isoprenaline in conscious cats were blocked by propranolol but not by thymoxamine suggesting the effect is mediated solely via excitatory beta-adrenoreceptors. 5 In anaesthetized cats prior i.c. administration of noradrenaline reduced the pressor responses induced by IIIv noradrenaline. 6 In conscious cats i.v. clonidine reduced pressor responses to IIIv noradrenaline without depressing peripheral vascular noradrenaline sensitivity. 7 The results suggest the involvement of excitatory and inhibitory alpha-adrenoreceptors and of excitatory beta-adrenoreceptors in central blood pressure control. It is also concluded that activation of inhibitory alpha-adrenoreceptors in the hind brain region can suppress the cardiovascular effects of stimulating excitatory alpha- and beta-adrenoreceptors located in the region of the third ventricle.

Anesthesia↗

Reduction of dislocated hip prosthesis in the emergency department using conscious sedation: a prospective study.

This prospective observational study aimed to determine the rate of success of reduction of dislocated hip prostheses using conscious sedation. In 101 consecutive patients presenting to the emergency department between August 2000 and February 2003 with a dislocated hip prosthesis, reduction was attempted using conscious sedation. The outcome measures of the study were (a) rate of success of the attempted reductions (b) rate of complication of the sedation or the procedure, and (c) rate of success in the three subgroups (based on degree of dislocation). The overall success rate was 62% (95% CI 53% to 71%). There were six complications: five related to sedation and one was a mild foot drop. The mean time to attempted reduction using conscious sedation was 1.83 hours and for an equivalent group who were excluded and subsequently required general anaesthesia the mean time was 10.9 hours. Reduction of isolated unilateral prosthetic hip dislocation using conscious sedation in the emergency department is safe and has a reasonable success rate. Prosthetic hip reduction can be attempted more quickly using conscious sedation than when awaiting general anaesthesia.

Arthroplasty, Replacement, Hip↗

The influence of renal nerves on electrolyte excretion in conscious and anesthetized rats fed or fasted overnight.

The role of the renal nerves in the electrolyte excretion of rats fed or fasted overnight was determined in conscious rats and anesthetized (Inactin) and surgically prepared rats. In conscious rats sodium excretion, as measured in a 1-h urine collection period after feeding or fasting overnight, was decreased with fasting with or without renal nerves. Renal nerve activity, as measured by norepinephrine turnover (inhibition of tyrosine hydroxylase by alpha-methyl-p-tyrosine), was not different between conscious fed or fasted rats and increased to the same extent in fed and fasted rats when anesthetized and surgically prepared. Anesthetized, surgically prepared rats infused with 5.0% glucose showed a denervation natriuresis if rats were fed overnight, but not if they had been fasted overnight. Potassium excretion in conscious and anesthetized rats was lower in fasted rats than fed rats with or without renal nerves. These data suggest (i) renal nerves are not involved in the renal response to an overnight fast in conscious rats, and (ii) in anesthetized, surgically prepared rat renal sympathetic tone is enhanced and denervation natriuresis occurs if rats are fed but not if fasted. Potassium excretion is a reflection of whether rats are fed or fasted and not whether they have renal nerves.

Anesthesia↗

Cardiovascular responses to intrathecal vasopressin in conscious and anesthesized rats.

Increases in mean arterial pressure and heart rate have been documented after the intrathecal administration of [Arg8]vasopressin (AVP) in rats. Prior studies in our laboratories with conscious rats indicated that these cardiovascular changes were associated with a marked hindlimb sensorimotor dysfunction. In this study, which represents the first systematic comparison of the effects of intrathecal AVP in conscious and anesthesized rats, we demonstrate that in conscious male Sprague-Dawley rats 1) the motor dysfunction induced by intrathecal AVP is accompanied by a rise in mean arterial pressure that is significantly greater than that produced by an equal intravenous dose of AVP, and 2) both paralytic and pressor effects of intrathecal but not intravenous AVP are blocked by the intrathecal administration of the V1-receptor antagonist d(CH2)5[Tyr(Me)2]AVP (V1-ANT) but are not blocked by intravenous phenoxybenzamine, hexamethonium, or [Sar1, Thr8]angiotensin II, an angiotensin II antagonist. In contrast, in anesthesized rats the arterial pressor response to intrathecal AVP was blocked by intrathecal V1-ANT, intravenous hexamethonium, and intravenous phenoxybenzamine. Furthermore, conscious but not anesthesized rats exhibited a tachyphylaxis to intrathecal AVP. These results indicate that intrathecal AVP produces both the cardiovascular changes and the sensorimotor deficits through interactions with centrally located V1-receptors. In addition, sympathetic catecholaminergic mechanisms mediate the rise in mean arterial pressure produced by intrathecal AVP in anesthesized rats, but they do not in conscious rats.

Animals↗

Hemorrhage effects on plasma ANP, NH2-terminal pro-ANP, and pressor hormones in anesthetized and conscious rats.

We examined the effect of hemorrhage on plasma NH2-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and atrial natriuretic peptide (ANP) in anesthetized and conscious rats. Blood (1.5 ml/time point) was withdrawn at 0, 10, 20, and 30 min. In anesthetized rats it caused decrease in mean arterial pressure and led to bradycardia in 2 min. Right atrial pressure decreased significantly after 12 min. However, plasma ANP did not change, and NT-pro-ANP actually increased from 481 +/- 55 to 609 +/- 73 pmol/l (P < 0.01) at 20 min and to 696 +/- 82 pmol/l (P < 0.01) at 30 min. Also plasma arginine-8-vasopressin (AVP) and epinephrine increased significantly at 30 min. No significant changes in plasma endothelin and norepinephrine were found. The increase in NT-pro-ANP after hemorrhage was not blocked by AVP V1-receptor, alpha- and beta-catecholaminergic receptor, or muscarinic-receptor antagonists. The plasma 125I-ANP disappearance curve was shifted to the right after hemorrhage in anesthetized rats, suggesting that the elimination of ANP was decreased. In conscious rats, heart rate and right atrial pressure did not change significantly after hemorrhage, and mean arterial pressure did not decrease until 22 min. NT-pro-ANP decreased from 1,467 +/- 146 to 1,072 +/- 130 pmol/l (P < 0.01) at 20 min and to 941 +/- 41 pmol/l (P < 0.01) at 30 min. Plasma ANP did not respond to hemorrhage in conscious rats. In conclusion, we found no change in plasma ANP during hemorrhage in either anesthetized or conscious rats, but we did find a significant increase in plasma NT-pro-ANP levels in anesthetized rats and a significant decrease in conscious rats. We suggest that this divergence may be due to different hemodynamic responses to hemorrhage.

Animals↗

Acute and chronic pulmonary vasoconstriction after left lung autotransplantation in conscious dogs.

We investigated the acute and chronic effects of left lung autotransplantation (LLA) on the left pulmonary vascular pressure-flow (LP/Q) relationship in conscious dogs. Continuous LP/Q plots were generated in chronically instrumented conscious dogs 2 days, 2 wk, 1 mo, and 2 mo after LLA. Identically instrumented normal conscious dogs were studied at equal time points post-surgery. LLA had little or no effect on baseline systemic hemodynamics or blood gases. In contrast, compared with normal conscious dogs, striking active flow-independent pulmonary vasoconstriction was observed 2 days post-LLA. The slope of the LP/Q relationship was increased from a normal value of 0.275 +/- 0.021 to 0.699 +/- 0.137 mmHg.ml-1.min-1.kg-1 2 days post-LLA. Pulmonary vasoconstriction of similar magnitude was also observed on a chronic basis at 2 wk, 1 mo, and even 2 mo post-LLA. Pulmonary vasoconstriction post-LLA was not due to fixed resistance at the left pulmonary arterial or venous anastomotic sites. Finally, systemic arterial blood gases were unchanged when total pulmonary blood flow was directed to exclusively perfuse the transplanted left lung. Thus, LLA results in both acute and chronic pulmonary vasoconstriction in conscious dogs. LLA should serve as a useful stable experimental model to assess the specific effects of surgical transplantation on pulmonary vascular regulation.

Animals↗

Importance of glycinergic and glutamatergic synapses within the rostral ventrolateral medulla for blood pressure regulation in conscious rats.

In this study we used a method that permits bilateral or unilateral microinjections of drugs into the rostral ventrolateral medulla (RVLM) of conscious, freely moving rats. There is only limited information about how sympathetic vasomotor tone is maintained by premotor RVLM neurons in conscious animals. It has long been known that glycine microinjection into the RVLM region leads to a decrease in blood pressure (BP) in anesthetized animals. In the present study we show that both unilateral and bilateral microinjection of glycine at the same dose used for anesthetized rats (50 nmol, 50 nL) into the RVLM increases BP in conscious animals. A similar response was also observed when the excitatory amino acid L-glutamate was microinjected into the RVLM. The microinjection of kynurenic acid into the RVLM did not change the basal level of BP but blocked the increase in BP after glycine or glutamate microinjection. A decrease in BP was only observed when low doses of glycine were used (1 to 10 nmol). We conclude that, in conscious animals, the hypertension occurring in response to high doses of glycine into the RVLM is dependent on glutamatergic synapses within the RVLM. A decrease in BP observed when low doses of glycine were used shows that in conscious animals, the RVLM, in association with other premotor neurons, is probably responsible for the maintenance of sympathetic vasomotor tone, because glycine is less effective in decreasing BP under these circumstances than in anesthetized animals.

Animals↗

Urodynamic effects of oxybutynin and tolterodine in conscious and anesthetized rats under different cystometrographic conditions.

BACKGROUND: Antimuscarinic agents are the most popular treatment for overactive bladder and their efficacy in man is well documented, producing decreased urinary frequency and an increase in bladder capacity. During cystometry in rats, however, the main effect reported after acute treatment with antimuscarinics is a decrease in peak micturition pressure together with little or no effect on bladder capacity. In the present experiments we studied the effects, in rats, of the two most widely used antimuscarinic drugs, namely oxybutynin and tolterodine, utilising several different cystometrographic conditions. The aim was to determine the experimental conditions required to reproduce the clinical pharmacological effects of antimuscarinic agents, as seen in humans, in particular their ability to increase bladder capacity. RESULTS: Intravenous or oral administration of tolterodine or oxybutynin in conscious rats utilized 1 day after catheter implantation and with saline infusion at constant rate of 0.1 ml/min, gave a dose-dependent decrease of micturition pressure (MP) with no significant change in bladder volume capacity (BVC). When the saline infusion rate into the bladder was decreased to 0.025 ml/min, the effect of oral oxybutynin was similar to that obtained with the higher infusion rate. Also, experiments were performed in rats in which bladders were infused with suramin (3 and 10 microM) in order to block the non-adrenergic, non-cholinergic component of bladder contraction. Under these conditions, oral administration of oxybutynin significantly reduced MP (as observed previously), but again BVC was not significantly changed. In conscious rats with bladders infused with diluted acetic acid, both tolterodine and oxybutynin administered at the same doses as in animals infused with saline, reduced MP, although the reduction appeared less marked, with no effect on BVC. In conscious rats utilized 5 days after catheter implantation, a situation where inflammation due to surgery is reduced, the effect of tolterodine (i.v.) and oxybutynin (p.o.) on MP was smaller and similar, respectively, to that observed in rats utilized 1 day after catheter implantation, but the increase of BVC was not statistically significant. In anesthetized rats, i.v. administration of oxybutynin again induced a significant decrease in MP, although it was of questionable relevance. Both BVC and threshold pressure were not significantly reduced. The number and amplitude of high frequency oscillations in MP were unmodified by treatment. Finally, in conscious obstructed rats, intravenous oxybutynin did not modify frequency and amplitude of non-voiding contractions or bladder capacity and micturition volume. CONCLUSION: Despite the different experimental conditions used, the only effect on cystometrographic parameters of oxybutynin and tolterodine in anesthetized and conscious rats was a decrease in MP, whereas BVC was hardly and non-significantly affected. Therefore, it is difficult to reproduce in rats the cystometrographic increase in BVC as observed in humans after chronic administration of antimuscarinic agents, whereas the acute effects seem more similar.

Animals↗