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PubMed1992

[Pharmacologic studies of antimotion sickness actions of ginger].

The pharmacologic actions related to antimotion sickness effects of ginger (Zingiber officinale Roscoe.) were studied. There was no significant effect on parameters of rotatory movement-induced electronystagmogram of rabbit after intravenous (i.v.) infection of ginger juice. The low amplitude fast wave pattern of electrocorticogram of rabbit changed to high amplitude slow wave pattern after i.v. injection of ginger juice. Rabbit gastric contraction in situ was shortly suppressed after ginger juice i.v. administration. In the isolated rat fundus strip preparations, however, ginger juice reduced the spontaneous contractile frequency, and enhanced the spontaneous contractile amplitude, which was followed by inhibition. Ginger juice produced longitudinal contraction of the guinea-pig isolated ileum, which was followed by rapid tachyphylaxis. This contraction effect was not affected by hexamethonium and 5-HT, but could be inhibited by cold storage, hyoscine, morphine, diphenhydramine, promethazine and substance P desensitization. Naloxone could eliminate this inhibition produced by morphine. By using dose-response relationship plot, non-competitive antagonisms were observed between ginger juice and Ach and between ginger juice and histamine in isolated guinea-pig ileum. It is suggested that the pungent constituents of ginger release substance P from sensory fibres. The released substance P in turn either stimulates cholinergic and histaminic neurons to release Ach and histamine, respectively, or produces direct muscle contraction by activating M and H1 receptors correspondingly. It is proposed that after being excited by substance P, M and H1 receptors are inactive temporarily and unable to be excited by agonists, therefore, ginger juice exhibits anticholinergic and antihistaminic action. Ginger juice produces antimotion sickness action possibly by central and peripheral anticholinergic and antihistaminic effects.

Animals↗
PubMed1992

Emergency treatment of headache.

The first approach in the emergency treatment of headache is the use of abortive measures in an attempt to forestall progression of early signs and symptoms. Abortive measures include analgesics, antiemetics, and anxiolytics; nonsteroidal anti-inflammatory drugs; ergots, generally preceded by administration of an antiemetic; conservative use of corticosteroids; major tranquilizers; and even narcotics (in certain extreme and selective situations). If abortive measures fail, IM or IV administration of dihydroergotamine mesylate, preceded by promethazine (IM) or metoclopramide (IM or IV) and followed by dexamethasone (IM or IV), is an effective emergency procedure. Every patient seeking care for headache from an emergency department should be instructed on how and where to obtain definitive follow-up and long-term treatment.

Emergencies↗
PubMed1992

[Atropine in the premedication of patients at risk. Its effect on hemodynamics and salivation during intubation anesthesia using succinylcholine].

Should atropine be administered for premedication? This question continues to be controversial; in particular, the combined administration of atropine and succinylcholine has been investigated with conflicting results by numerous researchers. The present study was carried out to assess the effect of premedication with atropine on hemodynamic variables and salivation in patients assigned to ASA class II and III. METHODS. Eighty ASA class II or III patients received pethidine 1.0 mg/kg and promethazine 0.5 mg/kg i.m. 30 min prior to induction of anesthesia and atropine, either 0.01 mg/kg i.v. 10 min or 0.01 mg/kg i.m. 30 min prior to a standardized anesthetic induction with alcuronium (precurarizing dose), thiopental, and succinylcholine. In the control groups (20 patients each), no atropine was given. Systolic, diastolic, and mean arterial pressures (MAP) were measured. The ECG was monitored for arrhythmias. Salivation was assessed semiquantitatively using swabs positioned within the pharyngeal space. RESULTS. Ten minutes after the administration of atropine i.v., a significant increase in heart rate (HR) was observed; this did not occur within 30 min after administration of atropine i.m. At the time of tracheal intubation, HR was significantly increased in both i.v. atropine risk groups. After atropine i.m., an increase in heart rate during intubation was observed in ASA class II patients only. No increase in heart rate occurred in the control groups during tracheal intubation. Neither i.m. nor i.v. atropine had any significant effect on blood pressure. Arrhythmias occurred in a few cases with both routes of administration; several instances of marked tachycardia were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[The use of propofol during diskectomy in neurosurgery].

The intravenous anaesthetic agent propofol has become more and more popular not only for induction but also for the maintenance of anaesthesia in all fields of surgery. For this purpose, different infusion rates and also combinations of propofol with opioids, nitrous oxide and volatile anaesthetic agents have been described. The present study was designed to find the best dosage regimen for short operations and rapid changes. The necessity for the frequently recommended standardized combination of propofol with opioids should be checked with respect to the cardiovascular effects. METHODS. A series of 60 patients (ASA I and II, age range 22-79 years) selected for discectomy were prospectively randomized to three groups. Half an hour before operation all patient received 0.5 mg atropine, 50 mg promethazine and 50 mg pethidine as i.m. premedication. In all groups anaesthesia was induced with propofol in a bolus dose of 2.5 mg/kg body weight over a period of approximately 45 s. After 5 mg atracurium the patients were intubated under 100 mg succinylcholine and normoventilated with 70% nitrous oxide and 30% oxygen. For relaxation 25 mg of atracurium were given. In group I propofol was administered in a dosage of 15 mg/kg body weight per hour for 10 min after induction. After this time the propofol infusion was reduced to 6 mg/kg body weight per hour. Group II received 0.1 mg fentanyl before induction. The dosage of propofol was similar to group I. In group III 0.1 mg of fentanyl was administered before induction and propofol was given with an infusion rate of 6 mg/kg body weight from the beginning. The following parameters were controlled and documented: systolic and diastolic blood pressure (SAP and DAP), heart rate (HF), end-expiratory carbon dioxide (eeCO2), inspiratory oxygen concentration (FiO2) and peripheral oxygen saturation (sO2). Recovery time was determined as the time from the end of the propofol infusion until eye-opening on command. RESULTS. In all groups anaesthesia could be induced and maintained without complications. There was a slight increase in SAP in group I after intubation, while in the groups with fentanyl a pronounced decrease of SAP was found simultaneously with induction of anaesthesia (Fig. 1). In group I HF showed significantly higher values after intubation and for the next 15 min than in group II and group III. A rapid and pronounced increase of end-tidal carbon dioxide occurred in the fentanyl groups with the beginning of spontaneous ventilation at the end of anaesthesia. There was a significantly longer recovery time in group II with fentanyl and initial higher propofol infusion rate. A correlation between dosage of propofol and recovery time could not be found. DISCUSSION. The results of this study demonstrate that a routine combination of propofol with opioids is not necessary even for painful surgical procedures if the propofol dosage is initially increased. There are differences in cardiovascular reactions between group I without and groups II and III with fentanyl, but in our patients these changes were of no clinical importance. An additional administration of fentanyl can prevent hypertensive reactions or tachycardia with intubation, but on the other hand fentanyl can also increase the cardial depression of propofol with a dangerous decrease in blood pressure and heart rate. Therefore in combination with opioids lower doses of propofol should be used for induction and maintenance of anaesthesia. If opioids are administered, signs of a residual postoperative respiratory depression have to be taken seriously.

Adult↗
PubMedDate not supplied

The in vitro activity of phenothiazines against Mycobacterium avium: potential of thioridazine for therapy of the co-infected AIDS patient.

Patients presenting with Acquired Immune Deficiency Syndrome (AIDS) are predisposed to co-infection with Mycobacterium avium. The management of such patients is problematic due to underlying immuno-incompetence and the high resistance of M. avium to most non-toxic compounds. Therefore, the need for effective agents is obvious. Because phenothiazines, especially the relatively mild thioridazine, have significant activity against Mycobacterium tuberculosis, we investigated the in vitro activity of chlorpromazine, thioridazine, promazine, promethazine and desipramine against a reference and clinical strains of M. avium. The results obtained show that whereas all of the phenothiazines employed in this study had an minimum inhibitory concentration (MIC) against the strains studied that ranged from ca. 10 to > 50 mg/L, as was previously shown for M. tuberculosis, thioridazine was the most active of the group against M. avium.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Preliminary studies on phenothiazine-mediated reversal of multidrug resistance in mouse lymphoma and COLO 320 cells.

The ability of phenothiazine derivatives to inhibit the transport activity of P-glycoprotein in resistant mouse lymphoma and MDR/COLO 320 cells was studied. A rhodamine 123 efflux from the above-mentioned neoplastic cells in the presence of tested compounds was examined by flow cytometry. Two of the phenothiazine derivatives, namely perphenazine and prochlorperazine dimaleate, proved to be effective inhibitors of the rhodamine efflux. Other tested phenothiazine derivatives (promethazine hydrochloride, oxomemazine, methotrimeprazine maleate, trifluoropromazine hydrochloride, trimeprazine) also modulated the intracellular drug accumulation in both resistant cell lines, however, they exerted additional cytotoxic effects. The differences observed between the effects of the test compounds on intracellular drug accumulation could be the outcome of differences in phenothiazine's chemical structure, which is crucial for drug-cell membrane interactions. The results of this study provide information about a new group of compounds that offer promise in multidrug resistance reversal in tumor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Intrathecal cefazolin-induced seizures following attempted discography.

This report describes a 39 year-old woman who underwent attempted discography and intradiscal electrothermal therapy (IDET) of the L5/S1 intervertebral disc. The procedure was abandoned after multiple unsuccessful attempts to cannulate the disc. The case was complicated by at least two lumbar dural punctures, confirmed by injection of nonionic contrast that contained 12.5 mg/mL of cefazolin, included for prophylaxis of discitis. About 45 minutes later the patient developed severe back pain. Shortly thereafter she became progressively agitated and confused, and developed intractable seizures and coma. Despite aggressive treatment the patient could not be resuscitated and expired several hours later. Convulsions were initially attributed to an adverse reaction to meperidine and promethazine, given for the back pain, however this explanation proved to be untenable. In addition, the accidental administration of an ionic contrast agent, such as Hypaque(R), was excluded. Based on a detailed review of the case and the literature, it was concluded that the patient succumbed from an unintentional dose of intrathecal cefazolin, which had been diluted in the nonionic contrast agent that was used to confirm needle placement. Available evidence indicates that cefazolin is a potent epileptogenic agent when given intrathecally. The facts of the case and the evidence supporting the conclusion are presented. It is recommended that cefazolin not be mixed with the contrast agent used to document initial needle placement during discography.

Journal Article↗
PubMedDate not supplied

Cosmeceutical properties of polysaccharides from the root bark of Ulmus davidiana var. japonica.

In Korea and China, Ulmus davidiana var. japonica has been used as a traditional oriental medicine for the treatment of difficulty in urination, skin inflammation, etc. In order to investigate the potential of a polysaccharide extract from Ulmus davidiana var. japonica as a cosmetic ingredient, we measured its moisturizing effect, photo-induced cytotoxicity, and anti-inflammatory effect. After hydrolysis, HPLC experiments showed that the composition of the polysaccharide extract was mainly rhamnose, galactose, and glucose. The molecular weight of the obtained Ulmus davidiana root extract was 20,000. The intrinsic viscosity was 90 dl/g. In a moisturizing test conducted through the measurement of water loss in a desiccator and of moisture content with a Corneometer CM820, Ulmus davidiana root extract showed almost the same moisturizing effect as hyaluronic acid. In an assay for inhibition of the H(2)O(2)-activated release of PGE2, IL-6, and IL-8 in normal human fibroblast cell lines, Ulmus davidiana root extract showed an inhibitory activity of PGE2 release in a dose-dependent manner (up to 85.9% at a concentration of 0.1%). The percent inhibition of the release of IL-6 was in the range of 45.6% to 64.5% (H(2)O(2) was used as the positive control). Moreover, the release of IL-8 was completely inhibited in the entire concentration range (>0.0025%). In a test of recovery from photo-induced damage after UVA irradiation (3 J/cm(2)), the cell recovery of human fibroblasts increased to levels two times higher than that of the positive control, which was UVA-damaged cells in the absence of Ulmus davidiana root extract (up to 60.2% at 3.0% of Ulmus davidiana root extract). In a photo-induced cytotoxicity assay in the presence of promethazine as a photosensitizer, Ulmus davidiana root extract showed approximately 48% of the increased cell viability of the control. Therefore, Ulmus davidiana root extract may be useful for the development of a cosmetic ingredient.

Cell Line↗
PubMed1991

[Mean equipotent blood pressure-lowering concentrations of halothane, isoflurane and enflurane during balanced anesthesia differ from conventional MAC-values].

Balanced anesthesia is a technique that allows control of blood pressure in patients with coronary artery disease. In order to evaluate the relative requirements of volatile anesthetics during basic opioid analgesia, 51 patients with unimpaired left ventricular function who were undergoing coronary artery bypass grafting during balanced anesthesia were investigated. They were randomly assigned to three groups, i.e. halothane (H), isoflurane (I), and enflurane (E). Permanent medications were maintained up to 12 h preoperatively. After premedication with flunitrazepam, promethazine and piritramide, anesthesia was induced with 7 micrograms/kg fentanyl, 0.3 mg/kg etomidate, and 0.1 mg/kg pancuronium and continued with fentanyl infusion (0.1 microgram/kg-1 min-1). Volatile anesthetics were applied in oxygen/air and adjusted to keep the mean arterial blood pressure within +/- 20% of the preoperative value. End-expiratory concentrations of volatile anesthetics were measured (Capnomac, DATEX) and averaged over time. The mean ages of the patients in the different groups were 60 +/- 7.6 years (H), 59 +/- 7.1 years (I), and 60 +/- 6.9 years (E). Four patients in the halothane group, six in the isoflurane group, and five in the enflurane group took beta-blockers preoperatively. The cumulative doses of fentanyl were: H = 0.80 +/- 0.17 mg, I = 0.85 +/- 0.16 mg, and E = 0.83 +/- 0.16 mg at the time of skin incision and H = 1.20 +/- 0.26 mg, I = 1.38 +/- 0.19 mg, and E = 1.24 +/- 0.25 mg at the beginning of extracorporeal circulation.2+ which are possibly the reason for the high O2-MAC value, which may be abolished during balanced anesthesia. However, both the negative inotropic and the vasodilatory effects of enflurane are more likely explanations for the results. It is concluded that 0.5 to 1.0 MAC of halothane, isoflurane, or enflurane used as equipotent components of balanced anesthesia for blood pressure control during aorto-coronary bypass grafting may differ considerably from the conventional MAC concept.

Aged↗
PubMed1991

[The effect of sufentanil on cerebral blood flow, cerebral metabolism and the CO2 reactivity of the cerebral vessels in man].

Sufentanil, a synthetic opioid that is 5-10 times as potent as fentanyl, has been suggested for use during neurosurgical procedures because it maintains cardiovascular stability and produces hypnosis without the use of additional anesthetic agents. Doses as low as 2.5 micrograms.kg-1 are reported to create deep levels of anesthesia as demonstrated by EEG changes to high-amplitude delta-waves. However, there are no reports concerning the effects of sufentanil on blood flow and metabolism in the human brain. The present study was designed to investigate the influence of high-dose sufentanil-O2 anesthesia on the cerebral circulation, metabolism, and the cerebrovascular response to CO2 in man. METHODS. Nine male and 2 female patients between 41 and 60 years of age who were scheduled for coronary artery bypass surgery were studied. Premedication consisted of flunitrazepam 2 mg orally and piritramide 15 mg and promethazine 50 mg i.m. 1 h before arrival in the induction room. Measurements were performed with the patients awake (I), after sufentanil 10 micrograms.kg-1 as an induction dose followed by 0.15 micrograms.kg-1.min-1 as an infusion with normocapnia (pa CO2 42.1 +/- 2 mmHg) (II), during hypercapnia (pa CO2 53.7 +/- 3.5 mmHg) (III), and during hypocapnia (pa CO2 31.7 +/- 2 mmHg) (IV). Cerebral blood flow (CBF) was measured using the argon wash-in technique. Cerebral venous blood was obtained from a catheter in the superior bulb of the right internal jugular vein. Cerebral metabolic rates of oxygen (CMRO2) glucose (Mgluc) lactate (CMlac) were calculated by multiplying the arterial-cerebral venous oxygen and substrate differences by CBF. The Anaerobic Index was calculated from the equation avD lactate x 100/2 x avD glucose = ANI (%) Cerebral electrical activity was recorded by aperiodic analysis of the EEG (Lifescan). RESULTS AND DISCUSSION. In the EEG sufentanil anesthesia was characterized by a decrease in the number of high-frequency waves and an increase in the number and amplitude of delta-waves, a pattern that did not change throughout the study period. Concomitantly, under normocapnic conditions high-dose sufentanil led to the significant decrease in CBF by 29% accompanied by an 18% increase in cerebral vascular resistance (CVR). CMRO2 decreased by 22% while CMRgluc and CMRlac changed only insignificantly such that the ANI, which represents the percentage of anaerobically metabolized glucose, essentially remained unchanged. Mean perfusion pressure declined by 18% but stayed within the range of autoregulation. Hypoventilation (III) was followed by an 82% increase in CBF as a result of a 55% reduction in CVR, whereas cerebral metabolic parameters did not show important changes when compared to measurement II. Hyperventilation (IV), on the other hand, produced a distinct fall in CBF by 56% to a value that was 21% below the one obtained under normocapnia. This was due to an increase in CVR of the same magnitude. There was a 31% rise in CMRO2, resulting in a decrease in cerebral venous oxygen tension, but in no case did it fall below the critical value of 20 mmHg at which tissue hypoxia becomes severe. Although CMRlac increased and CMRgluc did not significantly change, the ANI remained essentially unchanged, which suggests a predominantly aerobic metabolism. The increase in metabolic activity with sufentanil during hypocapnia might be caused by an alkalosis-induced stimulation of glycolysis. It might also be related to a reduction in the depth of anesthesia, although neither the EEG nor the hemodynamic parameters indicated this. This study shows that the coupling between CBF and metabolism is well maintained and that the cerebrovascular response to CO2 is unimpaired during high-dose sufentanil anesthesia.

Adult↗
PubMed1991

[Activity of plasma atrial natriuretic peptide level during acute rejection of kidney transplantation].

Plasma atrial natriuretic peptide (ANP) in 51 kidney transplant patients (KTP) during acute rejection (AR) was measured. All 51 KTP were divided in 3 groups. In the first group (16 subjects) patients were treated by azathioprine, predinisone and promethazine, in the second group (16 subjects) patients were treated by cyclosporine A and prednisone however in the third group (19 subjects) patients were treated by cyclosporine A, azathioprine and prednisone. Control group contained 15 subjects. ANP levels in KTP were measured four times: First time nearly 3 days before AR, second time immediately after recognition AR, third time after 3 days methylprednisone therapy and 4th time 3 days after stopping methylprednisone therapy. In all KTP before rejection ANP levels were slightly enhanced. During AR was observed statistically significant increase ANP levels in all KTP. After methylprednisone therapy plasma ANP level returned to basal (before rejection) level. Only before rejection a significant positive correlation was found between ANP and kidney function. All our result suggests participation of factors other than wicked kidney function in the pathogenesis enhanced ANP levels during AR. Kind of immunosuppressive therapy seems only a slightly influence on ANP levels in KTP before and after AR.

Adult↗
PubMed1991

Histaminergic mechanisms in experimental convulsions.

Effect of some histamine (HA) agonists and antagonists were assessed on electroshock (MES) convulsions in mice and rats. In mice, pretreatment with the HA precursor, l-histidine (100, 500 and 1000 mg/kg) precipitated seizures after a subthreshold (30 mA) stimulus. Both incidence (%) and tonic hind limb extensor phase (THE) were more than that in vehicle treated controls. The H1 blockers, pheniramine (25 mg/kg) and promethazine (25 mg/kg) both protected against (60 mA) MES and both incidence of convulsions and THE were reduced. A similar protective effect was not seen with either the H2 blocker, cimetidine (up to 200 mg/kg), or atropine (1 mg/kg). In rats, both the classical antihistamines blocked MES seizures, whereas, the H2-blocker, cimetidine, and atropine were, ineffective. Further, both H1 blockers were ineffective in antagonizing seizures induced by pentylenetetrazole, INH, caffeine or strychnine. These results are discussed in light of a possible HA-ergic regulation of experimental convulsions.

Animals↗
PubMed1975

[Modification of the adjuvans arthritis by carrageenin, compound 48/80, histamine- and serotonin antagonists, non-steroid antiphlogistics as well as protease inhibitors and their possible relations to inflammation mediators].

1. Injections of carrageenin (1,25 mg/kg i.v.) from the 1st to the 3rd day and then each 2nd or 3rd day inhibited paw swelling in adjuvant arthritis of the rat during the time of treatment. Injections from the 11th to the 15th day were ineffective. The level of plasma kininogen was slightly decreased but the total complement serum level was significantly lowered. 2,5 and 3 mg carrageenin/kg respectively were toxic after repeated injections. After a single administration the levels of plasma kininogen and of total serum complement were decreased by 50% although paw swelling was not affected. 2. Pentosane polysulfoester (25 mg/kg i.v.) did not influence paw swelling despite daily administration from the 1st to the 17th day. Heparin (10 000 IE/kg i.v.) was likewise ineffective. 3. Single or repeated injections of compound 48/80 (0,125-0,5 mg/kg i.v.; 1-5 mg/kg i.p.; 3-6 mg/kg s.c.), reserpine (0,2 mg/kg i.p.), cyproheptadine (5 mg/kg i.v.), bromolysergic acid diethylamide (2 x 2 mg/kg i.v.) or metiamide (10 mg/kg i.v.) were without effect on paw swelling. Neither did compound 48/80 effect the complement serum level. 4. Daily administration of chloropromazine (4-10 mg/kg p.o.) or of promethazine (10-15 mg/kg s.c. or p.o.) inhibited paw swelling in the first phase of adjuvant arthritis but not in the second one. 5. The soybean trypsin inhibitor (15 mg/kg i.v.) inhibited paw swelling significantly up to the 4th day, the Kunitz inhibitor (25 000 E/kg i.v.) was ineffective. 6. The content of prostaglandin E of the inflamed paws was increased threefold in both phases of arthritis. The results are discussed with regard to the putative role of mediators of inflammation (histamine, serotonin, kinins, prostaglandins, lysosomal enzymes, lymphokines, complement).

Animals↗
PubMed1990

[Chromatographic purity tests of various phenothiazine derivatives. I. Thin-layer chromatography].

Chromatographic purity tests of four phenothiazine derivatives chlorpromazine, levomepromazine, promethazine and trifluoperazine have been developed. The adsorptive and partition methods are suitable to the separation of the above substances and intermediates as well as side products of their productions. The most common impurities of final products were detected by qualitative purity tests. Densitometric quantitative determinations were carried out on silicagel layer using the solvent system cyclohexanebenzene-diethylamine. Quantity of intermediate impurities were 0.15-0.96%.

Antipsychotic Agents↗
PubMed1990

[Chromatographic purity tests of various phenothiazine derivatives. II. Gas chromatography].

Gas chromatographic purity tests of four phenothiazine derivatives chloropromazine, levomepromazine, promethazine and trifluoperazine have been described. Chromatographic system has been optimized that is suitable to the separation of the above substances and their intermediates as well as their side products. Thermostabilities of phenothiazine derivatives were determined, their thermal decompositions were investigated under gas chromatographic circumstances and the data obtained were completed with data of their thermoanalytical tests. Optimal conditions have been worked out and by applying them thermal decomposition of compounds could be minimized. Authors have drawn attention to formation of artificial products which could not be avoided therefore taking into account requirements of purity tests the application of the method is problematical.

Antipsychotic Agents↗
PubMed1991

Synergistic effects of INTERCEED(TC7) and heparin in reducing adhesion formation in the rabbit uterine horn model.

Surgical adjuvants are commonly employed to reduce the frequency of postoperative adhesion development after reproductive pelvic surgery. The ability of indomethacin, promethazine dexamethasone, Intralipid, progesterone, and heparin to reduce adhesion formation in combination with INTERCEED(TC7) (Johnson and Johnson Medical, Inc., New Brunswick, NJ), an absorbable barrier that alone reduces adhesion formation, was examined in a rabbit uterine horn model. A significant reduction in adhesion formation was only observed with the combination of INTERCEED(TC7) plus heparin. In addition studies, heparin delivery by intraperitoneal (IP) lavage, intravenous injection, or intra-abdominal instillation failed to demonstrate efficacy. Similarly, heparin delivery with other barriers or IP instillates (carboxymethylcellulose or 32% Dextran 70) failed to reduce adhesion formation. We conclude that INTERCEED(TC7) can be efficaciously utilized as a carrier to deliver heparin to traumatized surfaces, thereby reducing adhesion formation.

Animals↗
PubMed1991

Effects of chlorpromazine on PMN-mediated activities in vivo and in vitro.

Polymorphonuclear neutrophils (PMN) play a central role in the acute inflammatory response and functions associated with phagocytosis and bacterial killing, including lysosomal enzyme release and superoxide anion (O2-) generation, are also implicated in tissue injury. We have studied the modulation by chlorpromazine (CPZ) on the effects of lipopolisaccharide (LPS) in vivo in mice. Pretreatment with CPZ (4 mg/kg) and, to lesser extent, promethazine, inhibited LPS-induced hypoferraemia and lethality in mice. We have also observed that CPZ (1-15 microns) inhibited lactoferrin release by PMN in vitro, suggesting that this effect could be responsible for the inhibition of hypoferraemia. We have also evaluated the effect of CPZ on other PMN functions implicated in tissue damage and inflammation, chemotaxis and O2- production. CPZ inhibited both activities, although it had chemokinetic activity per se. These data indicate that CPZ is a modular of PMN functions in vivo and in vitro and this effect could be directly implicated in the protective action of CPZ against endotoxic shock.

Animals↗
PubMed1991

[The effect of halothane, enflurane and isoflurane on resistance and compliance in patients with asthma or chronic obstructive lung diseases].

In order to test the hypothesis that halothane is more effective and safer than enflurane and isoflurane in patients with reactive airway disease, a clinical trial was performed to compare these three agents in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS. After obtaining institutional approval and informed consent, 31 patients with bronchial asthma or COPD were studied (FEV1 less than 65% of FVC); all patients underwent extensive surgery of the paranasal sinuses. Premedication consisted of i.m. atropine and promethazine; anesthesia was induced with diazepam, fentanyl, etomidate, and succinylcholine and maintained with pancuronium and 50% N2O in O2 together with one of the volatile agents, halothane, enflurane, or isoflurane, selected at random. Patients were mechanically ventilated. On the basis of respiratory pressures, volumes, and flows, inspiratory (Rin) and expiratory (Rex) resistance and compliance (C) were calculated after induction (control), 15 min after the addition of the volatile agent (1.25 MAC), every 15 min during the surgical procedure, and at the end of the operation. RESULTS. In 1 case, airway resistance increased markedly a few minutes after administration of isoflurane. The results obtained in this patient were not included in the evaluation of the data. There were no statistically significant differences in the preoperative data or control values of Rin, Rex, and C among the three groups (n = 10 each). With the respective inhalational agents, Rin increased maximally between 3% (halothane) or 8% (enflurane) and 21% (isoflurane), Rex between 16% (halothane, enflurane) and 29% (isoflurane). For the most part, however, these changes were not statistically significant as compared with controls. Intergroup comparisons failed to reveal any statistically significant differences either. In all groups C decreased continuously to about 90% of control. DISCUSSION. The results show that in patients with asthma or COPD, airway resistance remains virtually unchanged during surgery and anesthesia under halothane or enflurane anesthesia. With isoflurane, however, the resistance may rise by a slight but not statistically significant extent. Furthermore, marked bronchospastic reactions occurred in 2 patients in the isoflurane group. Thus, the three volatile anesthetics studied were not found to be unequivocally safe and effective in preventing increases in bronchomotor tone. However, pharmacodynamic effects other than those on respiration (e.g., cardiovascular actions, arrhythmogenic threshold, metabolism, toxicity) must additionally be taken into consideration.

Adult↗