Changes in blood chemistries following prolonged enflurane anesthesia

In an effort to identify further the structural requirements for central dopamine receptor agonists, some monohydroxyl analogs of the known agonist 5,6-dihydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene were synthesized. They were examined for production of emesis in dogs and stereotyped behavior in rats. The most potent was 5-hydroxy-2-dipropylamino-1,2,3,4-tetrahydronaphthalene, which was more potent than apomorphine but less so than the dihydroxyl analog. The two enantiomers of the monohydroxyl analog were synthesized by conventional methods from an optically active intermediate, 2-benzylamino-5-methoxy-1,2,3,4-tetrahydronaphthalene. The resolution of this amine was performed with the aid of mandelic acid. Dopaminergic activity was found to be confined to the levo enantiomer. Requirements for both substitution and chirality in the tetralines were found to correspond closely to those known for the dopaminergic aporphines.     

Strategies for improving blood pressure control

OBJECTIVE: To investigate the sensitivity of echography vs magnetic resonance imaging (MRI) or computed tomography (CT) for detecting extraocular extension of choroidal malignant melanoma. DESIGN AND SETTING: Retrospective review at a university referral center. PARTICIPANTS: All patients with histopathologically proven extraocular extension of choroidal malignant melanoma evaluated at the Bascom Palmer Eye Institute, Miami, Fla, between January 1, 1988, and August 31, 1997. INTERVENTIONS: The histopathology records of all patients who underwent enucleation for choroidal malignant melanoma or biopsy of an extraocular nodule during the study period were reviewed. The records and imaging studies of patients who were found to have extraocular extension of choroidal malignant melanoma were then reviewed to determine the sensitivity of preoperative echography vs MRI or CT for detecting extraocular tumor extension. RESULTS: A review of 297 histopathology records identified 13 patients with extraocular extension of choroidal malignant melanoma. Three patients with only microscopic extraocular tumor extension were excluded from the study. Of the remaining 10 patients, all underwent ocular echography preoperatively, 5 underwent orbital MRI, and 2 underwent orbital CT scanning to evaluate for extraocular extension of tumor. Extraocular tumor extension was demonstrated in 10 patients (100%) with echography and in 2 (29%) of 7 patients with MRI (2 of 5 patients) or CT (0 of 2 patients). In no instance did MRI or CT demonstrate extraocular tumor extension that was not identified with echography. CONCLUSION: At this institute, ocular echography is more sensitive than MRI or CT for the detection of extraocular extension of choroidal malignant melanoma.     

Paclitaxel changes sympathetic control of blood pressure

Paclitaxel has become part of standard therapy in the treatment of ovarian and breast cancer. Concern has been raised about the effects of paclitaxel on cardiovascular function. Therefore, this study of the effects of paclitaxel on autonomic cardiovascular control was initiated. Eighteen women treated for ovarian or breast cancer were examined with autonomic cardiovascular function tests, once before the treatment and once after the second course of paclitaxel. Heart rate and blood pressure variability and changes in heart rate and blood pressure responses to the tests were measured. Baroreflex sensitivity was calculated from the Valsalva manoeuvre non-invasively. Paclitaxel did not change heart rate variability at rest compared with the pretreatment level. However, medium frequency variability of blood pressure was smaller after treatment with paclitaxel. Paclitaxel treatment did not impair the heart rate and blood pressure responses to the autonomic function tests. The results do imply that paclitaxel alters sympathetic control of blood pressure. Nevertheless, paclitaxel does not appear to precipitate autonomic cardiac neuropathy.     

The effect of epidural anesthesia on uterine activity and blood pressure

Because of the unresolved controversy regarding the effect of epidural anesthesia upon uterine contractility, it was decided to study its effect on a small number of patients. Intrauterine and intra-arterial continuous pressure, continuous fetal heart rate, and maternal heart rate recordings were obtained from at least 20 minutes before administration of the epidural anesthic until complete dilatation in these patients. Nineteen patients were in spontaneous labor, and 18 had labor stimulated with oxytocin. Plain lidocaine, 1 or 1.5%, was used in 12 patients (30 observations), and lidocaine with epinephrine, 1:200,000 was used in 26 patients (51 observations). Uterine contractions were calculated in Montevideo units for 60 minutes following the epidural anesthetic. The changes, if any, were compared in both groups. There was a significant decrease in uterine activity when epinephrine was added to the anesthetic solution, mainly a lessening of intensity. There were comparable decreases in systolic/diastolic blood pressure in both groups and compensatory tachycardia. In one case, severe hypertension was observed following administration of lidocaine epinephrine. It was concluded that the addition of epinephrine to the anesthetic solution predictably produces diminution of uterine activity, and it does not give "cardiovascular support" to the laboring patient.     

Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers

The effects of prolonged enflurane and halothane administration on urine-concentrating ability were determined in volunteers by examining their responses to vasopressin before anesthesia and on days 1 and 5 after anesthesia. A significant decrease in maximum urinary osmolality of 264 +/- 34 mOsm/kg (26 per cent of the preanesthetic value) was present on day 1 after enflurane anesthesia, whereas subjects anesthetized with halothane had a significant increase in maximum urinary osmolality of 120 +/- 44 mOsm/kg. Serum inorganic fluoride level peaked at 33.6 muM and remained above 20 muM for approximately 18 hours. Thus, the threshold level for inorganic fluoride nephrotoxicity is lower than previously suspected.     

The determinants of long-term blood pressure stability: control of trough blood pressure during sleep

Little is known regarding the prevalence and course of fatigue in cancer patients after treatment has ended and no recurrence found. The present study examines fatigue in disease-free cancer patients after being treated with radiotherapy (n = 154). The following questions are addressed. First, how do patients describe their fatigue 9 months after radiotherapy and is this different from fatigue in a nonselective sample from the general population (n = 139)? Secondly, to what degree is fatigue in patients associated with sociodemographic, medical, physical and psychological factors? Finally, is it possible to predict which patients will suffer from fatigue 9 months after radiotherapy? Results indicated that fatigue in disease-free cancer patients did not differ significantly from fatigue in the general population. However, for 34% of the patients, fatigue following treatment was worse than anticipated, 39% listed fatigue as one of the three symptoms causing them most distress, 26% of patients worried about their fatigue and patients' overall quality of life was negatively related to fatigue (r = -0.46). Fatigue in disease-free patients was significantly associated with: gender, physical distress, pain rating, sleep quality, functional disability, psychological distress and depression, but not with medical (diagnosis, prognosis, co-morbidity) or treatment-related (target area, total radiation dose, fractionation) variables. The degree of fatigue, functional disability and pain before radiotherapy were the best predictors of fatigue at 9-month follow-up, explaining 30%, 3% and 4% of the variance respectively. These findings are in line with the associations found with fatigue during treatment as reported in the preceding paper in this issue. The significant associations between fatigue and both psychological and physical variables demonstrate the complex aetiology of this symptom in patients and point out the necessity of a multidisciplinary approach for its treatment.     

Failure of enflurane and halothane anesthesia to inhibit lymphocyte transformation in volunteers

Changes in the peripheral blood leukocyte count and in the ability of lymphocytes to transform in response to phytohemagglutinin were studied in healthy volunteers undergoing prolonged enflurane or halothane anesthesia without coincident surgical operation. Anesthesia was associated with a modest leukocytosis that persisted into the first post-anesthesic day, primarily due to an influx of neutrophils into the circulation. There was no significant alteration, either during or following anesthesia, in the ability of the volunteers' lymphocytes to transform in response to phytohemagglutinin when compared with either preanesthetic values or unanesthetized controls. Depression of lymphocyte transformation does not appear to follow prolonged enflurane or halothane anesthesia in the absence of a surgical procedure.     

Role of renal interstitial pressure on chronic control of arterial blood pressure

We examined the modulatory effect of serotonergic activities on haloperidol-induced up-regulation of dopamine D2 receptors in rat striatum. Chronic treatment with haloperidol (0.1, 0.5 mg/kg, i.p., 3 weeks) increased the number of dopamine D2 receptors, while no increase was observed with atypical antipsychotic drugs clozapine (10 mg/kg) and ORG 5222 (0.25 mg/kg). Chronic treatment with MK 212, a serotonin (5-HT)2A/2C receptor agonist (2.5 mg/kg), or with citalopram, a 5-HT reuptake inhibitor (10 mg/kg), potentiated the haloperidol (0.1 mg/kg)-induced up-regulation of dopamine D2 receptor, while that with (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a 5-HT1A receptor agonist (0.1 mg/kg), had no influence on the dopamine D2 receptor up-regulation. Co-administration of ritanserin (1 mg/kg), a 5-HT2A/2C receptor antagonist, with a low dose of haloperidol (0.1 mg/kg), but not with a high dose of the agent (0.5 mg/kg), attenuated the dopamine D2 receptor up-regulation. Drug occupation of 5-HT2A and dopamine D2 receptors in vivo examined with use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was 69.8% and 45.1%, respectively, after the acute administration of haloperidol (0.1 mg/kg) plus ritanserin (1 mg/kg). This profile that 5-HT2A receptors were highly occupied compared with dopamine D2 receptors was similar to that of clozapine or ORG 5222. These results suggest that potent 5-HT2A receptor antagonism versus weak dopamine D2 receptor blockade may be involved in the absence of up-regulation of dopamine D2 receptors after chronic treatment with clozapine or ORG 5222.     

Blood pressure control during eye surgery under local anesthesia using pulse oximetry

The purpose of this study was to compare the surface pH level of three different type sealers after mixing at various time intervals in vitro. The cements were mixed according to the manufacturer's instructions. They were incubated to set in 100% humidity at 37 degrees C for 1 h, 24 h, 5 days, 8 days, 2 wk, 3 wk, 4 wk, 5 wk, and 7 wk. pH was calculated by a Twin pH meter. The pH levels of the three sealers were different at various time intervals (p < 0.0001). The resin-based cement had a acid pH level (pH < 7.0). The calcium hydroxide-based cement showed a higher alkalinity pH level (pH > 7.0). The zinc oxide-eugenol-based cement showed a similar pH level to the calcium hydroxide cement at the end of the measurement. We postulated that, in endodontic therapy when those healing is needed, the alkaline-based sealer is the choice.     

Effect of remifentanil on clinical and electroencephalographic parameters of depth of anesthesia in balanced anesthesia with propofol, enflurane or isoflurane

Electrophysiological parameters are well-suited to detect changes in cerebral function. The present study investigates whether balanced anaesthesia with remifentanil during nociceptive stimulation is associated with changes in clinical and electrophysiological parameters indicating inadequate depth of anaesthesia. Following IRB approval and written informed consent, 23 patients (ASA: I; age: 36 +/- 11) scheduled for elective gynaecological laparoscopy were included in the study. Without any premedication, anaesthesia was induced with remifentanil (1.0 microgram/kg bolus injection), propofol (0.5 mg/kg added by repetitive (10 mg) bolus injections every 10 s until unconciousness) and vecuronium (0.1 mg/kg). Following endotracheal intubation (normoventilation: PetCO2: 36 bis 38 mmHg), remifentanil infusion was started with continuous doses of 0.5 microgram/kg/min over 5 minutes and maintained with 0.25 microgram/kg/min during surgery. Remifentanil was randomly combined with propofol (group 1: 100 micrograms/kg/min; n = 7), enflurane (group 2: 0.5 MAC; n = 8) or isoflurane (group 3: 0.5 MAC; n = 8). Monitoring included: heart rate (beats/min), mean arterial pressure (mmHg), oxygen saturation (%), endtidal CO2 (mmHg) and endtidal enflurane and isoflurane (%). EEG: 2-channel recordings of Fz versus mastoid and ECG (artefact control) during steady-state anaesthesia and surgery. Following fast-fourier-transformation (4 s; 256/s; 0.5 to 35.0 Hz), spectral power densities were calculated for the selected frequency bands. Auditory evoked potentials (AEP; middle latency) were registered simultaneously after binaural stimulation via head-phones click-stimulation (6 Hz; 75 dB above hearing threshold; 512 stimulations per average). Bandpass was 0.01 to 2.0 kHz. Analysis: Na, Pa, Nb (latencies; ms) and peak-to-peak amplitudes (NaPa, PaNb; microV). EEG and AEP recording technique [15]. The study protocol included baseline values from pre-intubation, pre-surgery, the respective post-stimulation values (1 min, 3 min, 5 min) and all data at five-minute intervals during surgery until emergence from anaesthesia. During steady-state study conditions with defined remifentanil applications, mean data indicate that in response to nociceptive stimuli no changes in clinical or electrophysiological parameters were observed. In contrast to other studies using different anaesthetic techniques, the present data from remifentanil indicate very stable haemodynamic and electrophysiological parameters (EEG, AEP) during noxious stimulations. Adjustable and with no plasma accumulation, remifentanil demonstrates potent antinociceptive effects resulting in signs of adequate anaesthesia.     

Social and economic factors as obstacles to blood pressure control

Further improvement in blood pressure control at the population level will result from dealing with hard-to-solve problems, such as access to care, long-term management of a chronic disease, and societal influences on lifestyle. Additional knowledge and experimental data are needed, reinforced by clear public health choices in this direction.     

Vasoactive substances and long-term control of blood pressure and hypertension]

The relationship between panic expectancy, social demand and agoraphobic avoidance was investigated in a group of 48 panic disorder subjects. Subjects were observed surreptitiously while completing a naturalistic behavioral avoidance task (BAT) involving either a high or low social challenge task. Subjects in the high social challenge task avoided more compared to subjects in the low social challenge task. Prediction of panic made before entering the situation and type of social challenge condition (high/low) were the only variables that accounted for significant amounts of unique variance in prediction of BAT score. The results confirm previous findings regarding the relationship between panic expectancy and avoidance and suggest that social interaction and scrutiny is a factor in avoidance.     

The control of microvascular permeability and blood pressure by neutral endopeptidase

Plasma extravasation from postcapillary venules is one of the earliest steps of inflammation. Substance P (SP) and bradykinin (BK) mediate extravasation and cause hypotension. The cell-surface enzyme neutral endopeptidase (NEP) inactivates both peptides. Thus, absence of NEP may predispose development of inflammation and hypotension. We examined these possibilities in mice in which the NEP gene was deleted by homologous recombination. There was widespread basal plasma extravasation in postcapillary venular endothelia in NEP-/- mice, which was reversed by recombinant NEP and antagonists of SP (NK1) and BK (B2) receptors. Mean arterial blood pressure was 20% lower in NEP-/- animals, but this was unaffected by reintroduction of recombinant NEP and the kinin receptor antagonists. The hypotension was also independent of nitric oxide (NO), because NEP-/- mice treated with a NO synthase inhibitor remained hypotensive relative to the wild type. Thus, NEP has important roles in regulating basal microvascular permeability by degrading SP and BK, and may regulate blood pressure set point through a mechanism that is independent of SP, BK and NO. The use of NEP antagonists as candidate drugs in cardiovascular disease is suggested by the blood pressure data reported herein.     

Effect of indomethacin on blood pressure control during treatment with nitrendipine

This study tested the hypothesis that treatment with a nonsteroidal anti-inflammatory drug will not alter the hypotensive effect of a dihydropyridine calcium channel antagonist. Fifteen essential hypertensives (ages 58-80 years) had a supine diastolic blood pressure (DBP) < 100 mmHg after 4 weeks monotherapy with nitrendipine 5-20 mg twice daily. They entered a double-blind randomised crossover study in which the addition of indomethacin 25 mg three times daily was compared with placebo in treatment phases each of 4 weeks duration. Subjects were seen weekly and measurements in the last 2 weeks of each phase were compared. Supine blood pressure (mean +/- SE) was higher in the indomethacin phase (158 +/- 4/80 +/- 2) than in the placebo phase (154 +/- 4/76 +/- 3) (p < 0.01 for DBP). In 6/15 (40%) of subjects the increase in supine diastolic blood pressure with indomethacin was > 5 mmHg. Plasma urea was also increased in the indomethacin phase: 7.6 +/- 0.6 mmol/l compared with placebo: 6.3 +/- 0.5 mmol/l (p < 0.001). The study has demonstrated that concurrent treatment with the NSAID indomethacin impairs the blood pressure lowering effect of the dihydropyridine calcium channel antagonist nitrendipine. This increase in blood pressure with indomethacin in subjects treated with nitrendipine may represent either an independent pressor effect of indomethacin or a reduced vasodilator prostanoid contribution to the hypotensive effect of nitrendipine. This blood pressure increase may be sufficient to interfere significantly with clinical blood pressure control in some subjects.     

Effects of sulpiride isomers in the control of blood pressure in man

The effects of d-Sulpiride (25 mg i.v.) and 1-Sulpiride (25 mg i.v.) administration in the control of arterial blood pressure (ABP) and PRL-GH secretion have been analyzed in five normal male volunteers. It was observed a quite different action on ABP, 1-Sulpiride causing a long lasting hypotension and d-Sulpiride a short-lived hypertension. The correlation between ABP, heart rate and PRL-GH levels suggests a probable central cation for 1-Sulpiride and a possible peripheral action for d-Sulpiride effects on ABP.     

Topical laryngo-tracheal anesthesia and intraocular pressure in anesthesia for ophthalmic surgery

OBJECTIVE: The reflex response to orotracheal intubation provokes an increase of arterial pressure accompanied by an increase of chorioides volume and a consequent ocular hypertone. There are several methods to reduce the reflex response due to intubation. One of the most effective is topical anaesthesia of larynx and trachea. Experiments were directed to evaluate the efficacy of topical anaesthesia to reduce the intraocular hypertone due to orotracheal intubation. DESIGN: A prospective randomized mask study was conduct on patients undergoing ophthalmologic (anterior segment) surgery at the Eye Clinic of Florence University. METHODS: Intraocular pressure was measured by a Goldman tonometer at four times: T0 = basal, T1 = 2' minutes after induction of general anaesthesia, T2 = 2' minutes after laryngoscopy, T3 = 2' minutes after orotracheal intubation. At the same moments, systolic blood pressure, heart rate, rate pressure pro duct were measured. Patients were randomly divided in two groups: Group L (n = 10) in which was evaluated the efficacy of laryngotracheal topical spray of lidocaine 4% (2 ml) and Group F (n = 10) in which saline was used instead of anesthetic. The filling of the LTA kit (Abbott) was made by a person not involved in the experiments. DATA ANALYSIS: Student's t test for unpaired data. RESULTS: Topical anaesthesia reduces the increase of intraocular pressure, hypertension and rate pressure product due to intubation. The intraocular pressure reduces to 13% less than basal value in Group L and increase to 50% more than basal value in Group F. CONCLUSION: The topical anaesthesia of larynx and trachea is effective to reduce the intraocular hypertension due to the reflex response evoked by orotracheal intubation.