Inhibition of erythrocyte membrane ATPases with antisickling and anaesthetic substances and ionophoric antibiotics.

A study has been carried out into the effects of clinically important antisickling and anaesthetic substances and ionophoric antibiotics on the activities of (Na+, K+)- and (Ca+2, Mg2+)-ATPases of the human erythrocyte membrane. In general, these drugs, with the exception of nystatin, inhibit both types of enzymic activities but with varying degrees of efficacy. (Ca2+, Mg2+)-ATPases was more sensitive to the lipophilic anaesthetics and (Na+,K+)-ATPase to the ionophoric antibiotic, amphotericin B. These results are explained in the light of the partition coefficients of these drugs in erythrocyte membranes, their effects on the fluidity of the erythrocytes membranes, the changes they induce in the permeability properties of erythrocytes and the subsequent effect of procaine on sickling of erythrocytes, and their potential interaction with specific membrane components.

Effects of administration of oxytocin in association with gonadotropin-releasing hormone on luteinizing hormone levels in rats in vivo.

Gonadotropin-releasing hormone (GnRH) and oxytocin both stimulate the secretion of luteinizing hormone (LH), although with different characteristics. Therefore, interaction between oxytocin and GnRH in the control of LH may be postulated. We developed models for investigating whether oxytocin can modulate GnRH action on LH in vivo. Pentobarbitone is known to pharmacologically isolate the pituitary from hypothalamic GnRH. We found that after pentobarbitone anesthesia of female rats at proestrus, oxytocin caused a synergistically enhanced LH response to administered GnRH (p < 0.04). In a second series of experiments, female proestrous rats were anesthetized with althesin. This anesthetic allows transport of endogenous GnRH from the hypothalamus to the pituitary. In control animals, which received no exogenous hormone, there was a surge in the mean LH concentration on the evening of proestrus, indicating the presence of endogenous GnRH activity. Thus, the novel model enables detection of interactions of administered hormones with endogenous GnRH. Administration of GnRH plus oxytocin in the afternoon of proestrus caused a reduction (p < 0.01) in the mean level of LH observed in the evening. The reduction was larger than if GnRH alone was administered. Following althesin anesthesia, rats sometimes had low LH levels on the afternoon of proestrus. There was a statistically significant difference between the number of rats that received oxytocin plus GnRH and had low LH levels and the number with low LH levels in the control group (p < 0.02). Neither of the hormones administered alone had a significant effect. Thus, it appears that oxytocin accentuated the effect of GnRH in reducing LH concentrations in althesin-anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Course of murine leukemia retrovirus infection determined in vivo by magnetic resonance imaging.

Magnetic resonance imaging was applied to measure the volumes of spleens and lymph nodes of mice infected with three different leukemia retroviruses (LP-BM5 murine leukemia virus, Friend, and Rauscher) in vivo. Anesthesia by rapid intraperitoneal injection of Saffan was sufficient for magnetic resonance imaging and could be repeated at appropriate intervals. Eleven frontal magnetic resonance images through the abdomen with a center-to-center distance of 1.5 mm between adjacent slices were acquired simultaneously. To optimally demarcate spleens from the surrounding tissues, the magnetic resonance images were mildly T2-weighted for mice infected with LP-BM5 murine leukemia virus and mildly T1-weighted for those infected with Friend and Rauscher virus. Measurements requiring only 3 to 4 hours in groups of 24 to 28 mice were accomplished by using a standardized holder (i) accommodating two animals in the supine position and (ii) ensuring reproducible positioning in the magnetic resonance-instrument, and (iii) by reducing the number of phase-encoding steps of mildly T2-weighted magnetic resonance images from 256 to 128. Volumes of spleens and inguinal lymph nodes were calculated from the respective cross-sectional areas. The weights and magnetic resonance image-derived volumes of spleens and inguinal lymph nodes correlated well (r greater than 0.95). Despite large variations in the extent of splenomegaly and lymphadenopathy at any given time, the progression of the disease could easily be followed by repeating magnetic resonance imaging at intervals. Thus, statistically relevant results can be obtained in an infection model requiring the use of only a few animals.

Use of an emulsion of ICI 35868 (propofol) for the induction and maintenance of anaesthesia.

2,6-Diisopropyl phenol in a fat emulsion formulation (propofol) has been used to supplement 67% nitrous oxide in oxygen anaesthesia in 20 patients premedicated with morphine 0.15 mg kg-1 and atropine 0.6 mg, and undergoing body surface surgery. Following an induction dose of propofol 2.5 mg kg-1, the mean maintenance dose was 73.4 micrograms kg-1 min-1. When compared with 10 patients receiving Althesin to supplement nitrous oxide in oxygen in a similar manner, recovery was considerably faster following propofol. The only major side-effect associated with the use of propofol was pain on injection in nine out of 20 patients. When the patients receiving propofol were compared with a second control group (n = 11) in whom anaesthesia was induced with thiopentone 4 mg kg-1 and maintained with 1% halothane and nitrous oxide in oxygen, the former group showed a significant (P less than 0.01) decrease in the plasma cortisol concentration 30 min after the induction of anaesthesia. However, by 3 h after induction, the cortisol concentration in both groups was not significantly different from the baseline (preinduction) value. The mechanism of this decrease is not known. Investigation of the influence of the fat emulsion on blood coagulation and fibrinolysis revealed no differences when compared with patients receiving Althesin.

Efeitos do alfatesin sobre a atividade convulsivante da estricnina e do pentetrazol em coelhos / Effects of alphatesin on the convulsive activity of the strichinin and pentetrazol in rabbits

O uso de Alfatesin é acompanhado com freqüência de fenômenos excitatórios de natureza ainda näo esclarecida apesar de ser empregado, eventualmente, em crises de epilepsias. Por esse motivo resolvemos estudar os efeitos desse agente, isoladamente (0,1 kg1) e em associaçäo com pentetrazol (10 mg. kg-1) ou 0,1 ml de estricnina (0,2 mg.kg-1) por via venosa, em dez coelhos. As drogas foram utilizadas isoladamente e em associaçäo nos mesmos animais, em intervalos de quatro dias. Foram observadas: presença de reflexo córneo palpebral e de endireitamento, nistagmo, miose, tono muscular, ataxia, analgesia e convulsäo. A cada atributo foi conferida uma nota de 0 a 3, de acordo com a sua intensidade. Foi observado que o alfatesin, isoladamente, determina sedaçäo, hipotonia muscular, ataxia e perda do reflexo de endireitamento, mas näo induz analgesia. Associado ao pentetrazol e a estricnina reduz ou abole as manifestaçöes de estimulaçäo do sistema nervoso central características dessas drogas. Ainda é capaz de impedir o óbito induzido pela estricnina isoladamente. A explicaçäo para esses efeitos é discutida, necessitando de estudos mais sofisticados para seu esclarecimento

The effect of althesin, ketamine or pentothal on renal function in saline loaded rats.

Rats were prepared with chronic cannulae in the carotid artery, jugular vein and urinary bladder; they were then kept 2 days to allow recovery from surgery. A steady-state continuous saline diuresis was established, then various anaesthetic agents were injected and changes in the urine flow, sodium and potassium excretion rates, GFR, ERPF, ERBF and blood pressure were measured. Five groups of rats were studied: (1) control animals given saline in place of any anaesthetic agent, all parameters measured remained constant; (2) althesin (1.2 mg/kg), all parameters remained constant except for the blood pressure which decreased slightly for 5 min; (3) althesin (12 mg/kg); (4) ketamine (50 mg/kg); (5) pentothal (50 mg/kg). The above anaesthetics altered all of the measured parameters except urine output. Various mechanisms for these anaesthetic agents are discussed. In althesin anaesthetized rats, all the retarded renal parameters recovered within 30 min. It is concluded that for the study of renal function, if a brief anaesthesia is needed, althesin is a more suitable anaesthetic agent.

[Anesthetic induction with Althesin or diazepam in patients undergoing an aortocoronary bypass]. / Induction anesthésique avec Alfatésine ou diazépam chez des patients opérés pour pontage aorto-coronarien.

The haemodynamic effects of induction of anaesthesia with diazepam (group D) and Althesin (group A) were studied in 25 coronary patients under betablockers with good myocardial function. Haemodynamic variables monitored were vascular pressures, cardiac output and systolic time intervals. The effects of both drugs were observed when used alone (time I) and in combination with fentanyl, pancuronium and nitrous oxide (time II). The results seemed to show that Althesin (12.51% fall in SI and 10.79% increase in PEP/LVET) depressed myocardial function more than diazepam (no significant difference), but the introduction of fentanyl, pancuronium and nitrous oxide removed the differences between the drugs as to their effect on myocardial performance. These drugs added a depressant effect to diazepam (13.83% fall in SI and 15.77% increase in PEP/LVET) without increasing Althesin's negative inotropic effect. However, in group A at time II, the pulmonary arterial pressure, the wedge pressure and the pulmonary vascular resistance were significantly reduced, while they remained stable in the diazepam group.

Nalbuphine and Althesin anaesthesia. A controlled double-blind comparison for cystoscopy.

In a double-blind, randomized study of 52 unpremedicated outpatients undergoing cytoscopy, either nalbuphine 20 mg or saline 2 ml was given intravenously immediately before induction of anaesthesia with Althesin 0.05 ml/kg. Increments of Althesin 0.5 ml were used to maintain anaesthesia. The patients received nalbuphine required less Althesin than those who received saline (p less than 0.001) for a similar duration of surgery, and there was less movement during anaesthesia (p less than 0.001). During surgery hyperventilation was observed in the patients who received saline; those who received nalbuphine had lower respiratory rates and higher peak expired CO2 levels (p less than 0.001), and also a smaller increase in pulse rate (p less than 0.05). Recovery after surgery was faster in the patients who received nalbuphine than those who did not (p less than 0.05) and both patients (p less and anaesthetists (p less than 0.001) graded Althesin anaesthesia as better after nalbuphine than after saline. Intravenous nalbuphine 20 mg improved Althesin anaesthesia for cystoscopy without apparent disadvantages.

Comparison of the effects of Althesin, chloralose-urethane, urethane, and pentobarbital on mammalian physiologic responses.

Physiological responses to anesthetic doses of four chemically dissimilar agents, namely, Althesin, urethane, chloralose-urethane, and pentobarbital sodium were compared in rats. The tail-flick test revealed Althesin had greater antinociceptive potency than urethane, chloralose-urethane, and pentobarbital, but its duration of action was shorter than that of chloralose-urethane. Althesin produced minimal or no suppression of core body temperature and mean arterial pressure, and only moderate reduction of mean pulse pressure. The heart rate and respiratory rate of Althesin-treated rats were slower than those of chloralose-urethane and urethane-treated counterparts, respectively, but were not significantly decreased from normal controls. It is concluded that Althesin is a suitable anesthetic for short-term surgery and for studies of body temperature, heart rate, and mean arterial pressure. Because release of gonadotropin-releasing hormone into hypophysial portal blood can be observed under Althesin but is suppressed or blocked by chloralose-urethane, urethane, and pentobarbital, Althesin is the anesthetic of choice in studies concerned with the neural control of ovulatory hormone release.

Intravenous anaesthesia for minor surgery. A comparison of etomidate or Althesin with fentanyl and alfentanil.

Eighty patients undergoing minor surgical procedures entered a randomized, double-blind, between-patient comparison of fentanyl or alfentanil, with etomidate or Althesin for induction and maintenance of anaesthesia. Patients were more likely to feel pain on injection when anaesthesia was induced using etomidate or fentanyl, than when Althesin or alfentanil were given. There was no difference between the four groups in respect of the ease of maintenance of anaesthesia. Recovery of consciousness was significantly faster in the patients who received alfentanil than in those who received fentanyl. Overall, alfentanil with Althesin was the best combination studied.