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The effects of indomethacin on the systemic and regional vasodilator responses to minoxidil in the conscious dog.

To define the role of endogenous prostaglandin (PG) synthesis in the vasodilator response to minoxidil (MNX), whole body and regional hemodynamics were measured in conscious, MNX-pretreated dogs before and after the administration of the cyclooxygenase inhibitor indomethacin (INDO). Twenty minutes after an i.v. dose of 2.0 mg/kg, INDO did not affect the reductions in mean arterial pressure and total peripheral resistance achieved with 1.0 mg/kg of MNX i.v. INDO appeared to selectively reverse MNX's vasodilation in the skin and stomach, as vascular resistance in these two tissues increased to pre-MNX levels. Since INDO also exerts a selective vasoconstriction in the skin and stomach of conscious, nonpretreated dogs (Humphrey and Zins, 1983), the fact that skin and stomach resistances were near baseline with this drug combination implies that MNX continues to exert a net vasodilation in these vascular beds. In contrast to INDO's negligible hemodynamic interactions, MNX's vasodilation was nearly completely reversed by continuous i.v. infusions of the direct vasoconstrictor arginine vasopressin (ADH) administered at a mean dose of 35 mU/kg/min. MNX's reversal by ADH was not matched by maximally effective i.v. infusions of the alpha-adrenergic agonist norepinephrine at a mean dose of 0.4 micrograms/kg/min. These results indicate that the sustained peripheral vasodilation seen with MNX in the conscious dog is not dependent upon the synthesis of endogenous, PG-like dilator substances, as defined by concomitant INDO administration.

Animals↗

Single-injection method for evaluation of renal function with 3H-inulin and 14C-tetraethylammonium bromide in conscious unrestrained Sprague-Dawley rats.

A single-injection, double-isotope method for simultaneously determining glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in conscious, unrestrained rats was evaluated. 3H-inulin and 14C-tetraethylammonium bromide were used to determine GFR and ERPF, respectively. Using a modified, single exponential, 1-compartment, mathematical model, solute clearance was estimated, using a plasma radioactivity disappearance curve constructed from samples collected during a 60-minute period. In 12 healthy, conscious, adult male Sprague-Dawley rats, the mean (+/- SEM) GFR, ERPF, and filtration fraction were 5.65 +/- 0.40 ml/min/kg, 13.92 +/- 0.82 ml/min/kg, and 0.41 +/- 0.03, respectively. In 7 adult male Sprague-Dawley rats that had undergone a three-quarter nephrectomy 6 weeks prior to study, the mean GFR, ERPF, and filtration fraction were 2.69 +/- 0.36 ml/min/kg, 7.02 +/- 0.90 ml/min/kg, and 0.39 +/- 0.03, respectively. In 37 adult male rats in various stages of renal disease, the mean GFR and ERPF correlated significantly (r = 0.85, P less than 0.001 and r = 0.83, P less than 0.001, respectively) with the reciprocal of plasma creatinine. The single-injection, double-isotope technique yielded functional values similar to those reported for healthy rats in which other clearance methods were used. Using this technique, we were able to detect alterations associated with various degrees of renal functional loss. The technique enabled us to evaluate conscious, unrestrained rats, eliminated the need to collect urine, and required short blood collection times (60 min) and small volumes (0.1 ml) of plasma.

Animals↗

[Recovery of consciousness after prolonged coma in patients with severe craniocerebral injuries].

The authors specify and describe 7 stages of regaining consciousness by patients who had been in coma from 11 to 180 days, including opening of the eyes; fixation of the eyes on an object; recognition of close relatives; understanding of directly addressed speech; patient's own speech; amnestic confusion; consciousness with all formal signs of being clear. The condition of the patients at these stages is compared with EEG findings suggestive of the functional disintegration of the brain as a system in comatose patients, the vegetative status and the restoration of connections between different departments of the brain corresponding to the recovery of long absent consciousness of patients. It is concluded that at the current stage of medical sciences the maximum duration of coma compatible with the subsequent full recovery of mental activity of the patient under 30 years does not exceed 11 days.

Adolescent↗

Effects of the renal vasodilator prodrug CGP 22 979A and its parent compound CGP 18 137A on renal and central hemodynamics in conscious spontaneously hypertensive rats.

In a previous study we reported that the renal prodrug CGP 22 979A (N-acetyl-L-glutamic acid-N-[N2-(5-n-butyl-2-pyridyl)-hydrazide) causes selective renal vasodilation in conscious spontaneously hypertensive rats (SHR) in doses up to 10 mg/kg. The hydralazine-like parent compound CGP 18 137A (2-hydrazino-5-n-butyl-pyridine) causes general vasodilatation. In the present study we report on renal hemodynamics, excretion of water and sodium and central hemodynamic effects of CGP 18 137A and CGP 22 979A in conscious, unrestrained SHR. CGP 18 137A (1 mg/kg) reduced effective renal plasma flow [measured as plasma clearance of [125I]p-aminohippuric acid] and glomerular filtration rate (measured as plasma-clearance of 51Cr-EDTA), in the first hour after injection. CGP 22 979A (3-30 mg/kg) dose-dependently increased effective renal plasma flow, but not glomerular filtration rate thus reducing filtration fraction. In spite of the lack of increase of glomerular filtration rate, CGP 22 979A increased excretion of sodium and water in a separate group of SHR. CGP 18 137A reduced renal excretory function slightly. In another group of conscious SHR we studied the effects of CGP 18 137A and CGP 22 979A on central hemodynamics. These animals had an electromagnetic flow-probe on the ascending aorta, to measure cardiac output (CO). Mean arterial pressure was measured from a chronic catheter in the abdominal aorta. Total peripheral resistance (TPR) and stroke volume were calculated. CGP 18 137A (0.3-1 mg/kg) reduced mean arterial pressure and TPR whereas CO increased immediately after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of experimental hydrothorax on the cough reflex in conscious cats.

The authors induced experimental hydrothorax in cats by injecting dextran into the pleural cavity under brief N2O anaesthesia. They examined the parameters of cough -- elicited by mechanical stimulation of the airway mucosa -- and blood gas and pH values under normal conditions and after the injection of 50, 100, 200 and 250 ml dextran. The tests were always performed 30 min after terminating anaesthesia, i.e. in conscious animals. The free fluid in the thorax was found, in conscious cats, to reduce the inspiratory values of cough, but to have no effect on cough expiration. This is in agreement with previous findings showing that the intensity of a cough expiration does not always depend on the intensity of the preceding cough inspiration. According to this finding, the decrease in the expiratory values of cough observed during experimental pleurisy cannot be due to the actual exudate. In cats, experimental hydrothorax in doses of 200 and 250 ml leads to respiratory insufficiency. The authors further found that, for the study of interoception in the airways of conscious cats, which requires experimental induction of pathological conditions under brief anaesthesia, nitrous oxide is a convenient anesthetic.

Animals↗

Age at first conscious ejaculation: a milestone in male puberty.

The age of occurrence of the first conscious ejaculation was registered in 263 boys belonging to two categories: (1) 128 boys (70 normal controls, 22 boys with unilateral cryptorchidism with normal puberty, and 36 boys with delayed puberty) who had been under regular follow-up throughout puberty. All underwent a complete physical examination at intervals of 3 to 6 months, and in most a wrist X-ray was made within three months of the first ejaculation. (2) A group of 135 boys examined and questioned at their school served as additional controls. Eighty of these reported ejaculations. Despite a wide range in the chronological age at occurrence of the first conscious ejaculation, the mean bone age in all groups, including that with delayed puberty, was 13 1/2 +/- 1/2 years (SD), with a range between 12 1/2-15 1/2 years. There was no correlation between the age at first ejaculation and testicular volume, pubic hair or penis length. It is proposed that the age at the first conscious ejaculation be used as an index of maturation in male puberty.

Adolescent↗

Leakage of angiotensin converting enzyme inhibitors from the cerebral ventricles into the peripheral circulation in conscious, spontaneously hypertensive rats.

The inhibitory effects of SQ14225 and MK421 injected into the lateral brain ventricle (i.c.v.) and intravenously (i.v.) on pressor responses to intravenous (i.v.) angiotensin I(AI, 400 ng/kg i.v.) were compared in conscious spontaneously hypertensive rats (SHR). Both the i.c.v. and i.v. inhibitors suppressed the increase in blood pressure produced by intravenous injections of AI in a dose dependent manner. The inhibition of pressor responses to i.v. AI were rapid in onset and decayed with time following i.v. captopril and MK421, while the effects of i.c.v. inhibitors were slower in onset and were maintained for a longer time. The activity of MK421, either i.v. or i.c.v. persisted for longer compared to that of SQ14225 in conscious SHR. It was concluded that SQ14225 and MK421 readily leaked from the brain ventricles to the peripheral circulation and this observation suggested that the central hypotensive effects of these inhibitors might be partly attributed to peripheral blockade of angiotensin I conversion in conscious SHR.

Angiotensin-Converting Enzyme Inhibitors↗

Cardiovascular effects of tropacocaine in conscious and anesthetized rabbits: lack of evidence for neuro-cardiac interactions and acute neurotoxicity.

The cardiovascular effects of tropacocaine, a structural analog of cocaine, were investigated in both conscious and anesthetized New Zealand white rabbits to determine if such effects were mediated through the CNS as had been demonstrated with cocaine, i.e., did a neuro-cardiac pathway exist? To facilitate the requisite cardiovascular measurements in both urethane- and pentobarbital-anesthetized animals, the right femoral artery and vein were cannulated for the measurement of arterial blood pressure and subsequent delivery of drugs, respectively. In addition, urethane-anesthetized animals had a branch of the left renal nerve isolated and multiunit renal nerve activity was monitored to obtain measures of sympathetic nerve activity originating from the CNS. Animals utilized in conscious experiments were surgically prepared 3 days prior to drug administration by placing canulae in the femoral artery and vein that were tunneled subcutaneously to the back between the scapulae. ECG and respiratory activity were also monitored in each animal. Doses of 0.3, 1, 3, and 10 mg/kg of tropacocaine were administered in both an ascending and descending fashion at 15 min intervals to 5 animals in each group, i.e., conscious, urethane-, and pentobarbital-anesthetized. In urethane-anesthetized animals a comparison was made between sympathetic renal nerve activity, systolic and diastolic blood pressure, respiratory rate, and heart rate. No pressor effects were observed and the changes in renal nerve activity could not be assigned as the cause of the observed depressor effects at the higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗

Involvement of monoamine uptake inhibition and local anesthesia in the cardiovascular response to cocaine in conscious rabbits.

The cardiovascular effect of cocaine in rabbits was examined for peripheral and central components and for the contribution of the primary actions of cocaine, i.e., inhibition of the high affinity uptake mechanisms for monoamines and local anesthesia. In pithed rabbits with electrically stimulated sympathetic outflow (2 Hz), cocaine (0.2-5 mg kg-1) lowered the clearance of [3H]norepinephrine from plasma and increased the plasma norepinephrine concentration. Cocaine (0.2 and 1 mg kg-1) increased blood pressure and heart rate, whereas after 5 mg kg-1 heart rate and blood pressure decreased briefly and then recovered. In conscious rabbits, cocaine (0.2 and 1 mg kg-1) reduced renal sympathetic nerve activity and tended to reduce blood pressure and heart rate. Cocaine (5 mg kg-1) increased sympathetic nerve activity, blood pressure and the plasma norepinephrine and epinephrine concentrations. The effects of the lower doses were abolished in animals pretreated with oxaprotiline, but were not changed in animals pretreated with fluvoxamine or SCH 23390 (R-(+)-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol) + sulpiride. The effects of cocaine (5 mg kg-1) were attenuated by SCH 23390 + sulpiride but were not changed after oxaprotiline or fluvoxamine. Procaine (15 mg kg-1) mimicked the effects of cocaine (5 mg kg-1) on blood pressure and renal sympathetic nerve activity. Blood pressure also was increased by lidocaine (6 mg kg-1). It is concluded that cocaine enhances peripheral sympathetic neuro-effector transmission. In conscious rabbits, however, low doses fail to raise blood pressure because they simultaneously depress central sympathetic tone by blockade of the uptake of norepinephrine in the central nervous system. High cocaine doses cause sympathoexcitation in conscious rabbits. The mechanism seems to be dual: blockade of dopamine uptake in the central nervous system and a (peripheral or central) local anesthetic action.

Anesthetics, Local↗

Effect of cumulative doses of NG-nitro-L-arginine methyl ester on coronary blood flow of anesthetized and conscious dogs.

To examine the effect of cumulative doses of NG-nitro-L-arginine methyl ester (LNAME), an inhibitor of nitric oxide synthesis, on coronary blood flow, basal left circumflex artery blood flow and acetylcholine-induced flow increment were observed in anesthetized and conscious dogs. Four doses of LNAME (10(-5) M, 10(-4) M, 10(-3) M and 10(-2) M in the left circumflex artery blood were cumulatively infused into the left circumflex artery. All dogs were pretreated with 8-phenyltheophylline and acetylsalicylic acid to inhibit endogenous adenosine and vasodilator prostaglandin, respectively. In anesthetized dogs (n = 10), systolic blood pressure was increased with 10(-2) M of LNAME and heart rate was decreased with > or = 10(-3) M of LNAME. All doses of LNAME significantly decreased the left circumflex artery blood flow in a dose-dependent manner, without affecting the rate-pressure product. The acetylcholine-induced flow increment was significantly attenuated with all doses of LNAME. However, no further attenuation was induced by > or = 10(-3) M of LNAME and the maximal dose did not completely abolish the effect of acetylcholine. In conscious dogs (n = 7), LNAME showed similar effects to those seen in anesthetized dogs: the left circumflex artery blood flow decreased with > or = 10(-4) M of LNAME, without affecting the rate-pressure product; the acetylcholine-induced flow increment was attenuated with > or = 10(-4) M of LNAME, but not completely abolished. Thus, there is a basal nitric oxide release from the endothelium in the coronary resistance vessels of anesthetized and conscious dogs. However, (an)other mechanism(s) than the L-arginine-nitric oxide pathway seem(s) to be involved in the acetylcholine-induced vasodilatation.

Acetylcholine↗

Critical appraisal of pressure-frequency relation for estimation of diaphragm function in conscious calves.

A method yielding functional diaphragmatic variables in conscious animals is crucially needed to determine whether concepts and conclusions drawn from deeply anesthetized, highly instrumented clinically normal animals can be extrapolated to patients. Transdiaphragmatic pressure (Pdi) was, therefore, measured in 20 conscious calves during supramaximal transvenous bilateral stimulations of the phrenic nerves (pulse duration, 0.2 milliseconds; pulse frequency, 1, 10, 20, 30, 40, 70, and 100 Hz). Constancy of phrenic activation and precontraction length and geometry was ensured by respectively monitoring the amplitudes of right and left mass action potentials and triggering each activation train at end-expiratory lung volume against an occluded airway. Repeated phrenic activation and pressure recording procedures were well tolerated, safe, specific, and able to achieve constant and symmetric diaphragmatic tetanic contractions for prolonged periods. The Pdi increased with frequency of stimulation, so that, at 10, 20, 40, and 70 Hz, the mean +/- SD generated Pdi was 33 +/- 5, 65 +/- 8, 82 +/- 6, and 94 +/- 6% of Pdi at 100 Hz, respectively. The general shape of the Pdi-frequency relation and the absolute values of the generated Pdi were reproducible at 10-hour intervals despite CO2- or resistor-induced substantial changes in breathing pattern. It is concluded that this experimental model provides a reliable assessment of diaphragm function in conscious animals and can be used to study diaphragmatic contractility.

Action Potentials↗

[Variation of plasma platelet activating factor during development and reversal of hypoxic pulmonary hypertension in conscious sheep].

A model of hypoxic pulmonary hypertension was made in conscious sheep, and plasma platelet activating factor (PAF) were measured by radioimmunoassay method during the beginning, progression and reversal of hypoxic pulmonary hypertension. The main results were as follows: (1) Under hypoxic condition for 4 days, the conscious sheep develops hypoxemia and marked hypoxic pulmonary vasoconstriction (HPV). These response were reversible. (2) At the beginning of hypoxia, plasma PAF increased, but did not continually increase with hypoxic prolongation and development of HPV. (3) Upon cessation of hypoxia with reversal of pulmonary hypertension, plasma PAF did not show any parallel decrease. These results indicate that plasma PAF is in no way involves in the development of HPV in conscious sheep.

Animals↗

Clues to patient dissatisfaction with conscious sedation for colonoscopy.

OBJECTIVES: Most colonoscopy is performed using conscious sedation to facilitate the procedure. However, little is known about which patients are dissatisfied with sedation and why. The goal of this study was to examine whether certain patient- and procedure-specific variables are associated with patient dissatisfaction. METHODS: A total of 403 consecutive outpatients underwent colonoscopy during a 4-month study period. Of 342 patients who met entrance criteria, 328 completed the initial questionnaire and were enrolled. Subjects received standard conscious sedation; after colonoscopy, the primary endoscopist and nurse recorded the level of sedation as adequate or inadequate. Twenty-four to 72 hr after the procedure, an independent observer contacted the subjects by telephone and asked whether they were satisfied with the level of sedation achieved during the colonoscopy. A number of patient- (age, gender, anxiety level, and educational background) and procedure-specific variables (waiting time and procedure type, difficulty, and duration) were analyzed to determine their association with patient dissatisfaction. RESULTS: Forty-eight patients (15%) were dissatisfied with sedation. Univariable analysis showed that females, anxiety, higher education (at least 1 yr of college), procedure duration > or = 60 min, and procedure difficulty were all associated with the dissatisfaction with sedation (p < 0.05). Multivariable analysis revealed that only higher education (p = 0.009) and longer procedure duration (p = 0.018) were associated with patient dissatisfaction. CONCLUSIONS: Highly educated patients and those who underwent longer procedures were more likely to be dissatisfied with conscious sedation used for colonoscopy. A thorough discussion of expectations and/or patient-controlled sedation might improve satisfaction with colonoscopy in educated patients. Regular supplementation of sedation, termination of a lengthy procedure with the offer of a further attempt at a later date, and referral to a more experienced endoscopist when appropriate might all improve patient satisfaction with colonoscopy.

Anxiety↗

A study on withdrawal related haemodynamic response in chronic propranolol treated conscious rats.

Single dose of propranolol hydrochloride (5 mg/kg, i.p.) caused significant fall in heart rate (HR) but not in systolic blood pressure (SBP) in normotensive conscious rats. Multiple doses of propranolol (5 mg/kg, i.p., twice-a-day for 5 wk) caused significant fall in both HR and SBP at 2 wk and 4 wk in normotensive conscious rats. Sudden withdrawal of propranolol at 5 wk caused a significant blood pressure upswing and tachycardia between 12-24 h followed by normalization of both blood pressure and heart rate. The study documents a possible model of rebound hypertension in normotensive conscious rats.

Animals↗

A biting commentary on monitored anesthesia care with conscious sedation.

In summary, a continued emphasis needs to be placed on better operationalization of the concept of MAC and its components, not merely for reimbursement, but for practice sake. Quality risk evaluation and patient assessment guidelines unique to MAC and conscious sedation need to be established and closely adhered to. In 1988, the AANA Board of Directors adopted suggested guidelines for registered professional nurses engaged in the administration of intravenous conscious sedation. These guidelines were an addendum to Position Statement 2.2 entitled "Qualified Providers of Conscious Sedation" and are found in the Professional Practice Manual for the Certified Registered Nurse Anesthetist. It is incumbent upon all CRNAs who provide such services to not only be familiar with but also practice in accordance with these guidelines. Finally, as HCFA directs each Medicare carrier to determine when MAC is the appropriate standard of care, we as providers must recognize the same. Within each case scheduled under MAC lies the challenge to provide and maintain a high degree of vigilance in perhaps the more minor surgical procedure, while always anticipating and recognizing the potential for the unexpected that can make it hard for any professional to swallow.

Aged↗

[Alloesthesia without impairment of consciousness after right putaminal small hemorrhage].

Alloesthesia is a condition in which a sensory stimulus, given on one side of the body, is perceived to be at the corresponding area on the opposite side. In our previous study (Kawamura, Hirayama et al., 1987), we suggested that it may be useful for localization because this phenomenon was observed most frequently in patients with a right putaminal hemorrhage of medium or large size, an average of 42 ml on CT scans, presenting a slight disturbance of consciousness and, in about half of the patients, anosognosia. We also suggested that since alloesthesia is produced not only in cerebral but also in spinal cord lesions, it seems to represent an elementary sensory disturbance of sensory pathways, not a higher cortical dysfunction. We recently observed alloesthesia in two other patients with smaller right putaminal hemorrhages, 7 ml and 6 ml, respectively, who exhibited no disturbance of consciousness, but had impairment not only of superficial but also of proprioceptive sensations. In Patient 1, superficial sensations were intact on admission, except those on the left side of the face. Cortical somatosensory evoked potentials (SEPs) after stimulating the median nerve were measured on Patient 1 on the 11th hospital day when a left hemihypalgesia had developed due to enlargement of the hematoma from 7 to 14 ml. Stimulation of the clinically affected side (left) evoked no N20 from the contralateral scalp. Right-sided stimulation was normal. The fact that both patients showed alloesthesia with no accompanying disturbance of consciousness supported our view of its mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Systemic hemodynamics, renal function and hormonal levels during inhibition of neutral endopeptidase 3.4.24.11 and angiotensin-converting enzyme in conscious dogs with pacing-induced heart failure.

The systemic hemodynamic, renal and hormonal responses to SQ 28,603 (N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-beta-alanine) the selective inhibitor of neutral endopeptidase 3.4.24.11, the angiotensin-converting enzyme inhibitor captopril and their combination were determined in conscious dogs after 1 or 3 weeks of rapid ventricular pacing. Coadministration of captopril (100 or 10 mumol/kg i.v.) and SQ 28,603 (10 mumol/kg i.v.) significantly reduced mean arterial pressure, systemic vascular resistance and renal vascular resistance and increased cardiac output, stroke volume and renal blood flow in the conscious dogs paced for 1 week. This pattern of hemodynamic improvement was not predicted by the activity of the individual inhibitors. The combination of inhibitors did not significantly increase sodium excretion because of the variability introduced by the depressor activity; however, the pressure-natriuresis curve was steeper and shifted leftward, indicating that sodium excretion was maintained at lower renal perfusion pressures. The increases in urinary and plasma levels of cyclic GMP and atrial natriuretic peptide stimulated by SQ 28,603 were not affected by captopril. The data indicated that the hemodynamic and renal responses produced by SQ 28,603, presumably by elevating atrial natriuretic peptide levels, were enhanced by suppression of angiotensin II or that the combination of inhibitors protected other vasodilator/natriuretic peptides from degradation. Qualitatively similar responses to SQ 28,603, captopril and the combination of inhibitors were obtained in dogs paced for 3 weeks. In summary, the combined angiotensin-converting enzyme and neutral endopeptidase 3.4.24.11 inhibitors improved systemic hemodynamics and maintained renal function in conscious dogs with pacing-induced heart failure.

Alanine↗

Conscious midazolam sedation in third molar surgery--aspects of post-operative patient evaluation.

This study was conducted on 426 patients undergoing third molar surgery to evaluate their opinion on surgery and the follow-up period concerning postoperative behaviour, pain, and complaints. Two groups were formed as patients had to choose between local anaesthesia only or additional conscious sedation by means of intravenous midazolam (0.1 mg/kg). Women and younger patients preferred conscious sedation. Surgery was described as significantly less distressing by the sedated group. No difference in the evaluation of the follow-up period between both groups existed. Patients of the midazolam group took more analgesics, tended to stay longer in bed and reported on protracted cooling. Non-sedated persons older than 30 years complained about a slower decrease in postoperative pain. According to these findings, sensitive, cautious patients tend to prefer conscious sedation which is reflected in their behaviour. No relationship between the evaluation of surgery itself and the follow-up period could be found.

Adolescent↗