Differences of ropivacaine and bupivacaine relevant to antiinflammatory activity, platelet aggregation and antioxidant activity in vitro.

Ropivacaine and bupivacaine affect the in vitro growth of rat fibroblasts and monkey kidney Vero cells with bupivacaine generally showing the stronger effect. Up to 3 mM concentration the two anesthetics affect the expression of genes differently for CD2, CD3 gamma, CD40L, IL-2, IL-2R alpha, IL-2R beta, IL-2R gamma, IL-4, and IL-4R during activation of human lymphocytes, with bupivacaine showing the higher effect. Human platelet aggregation is inhibited by the two anesthetics which also show an antioxidant effect on lipid peroxidation of rat liver microsomes. In both cases bupivacaine seems more active than ropivacaine.

Combined effect of propofol and GSNO on oxidative phosphorylation of isolated rat liver mitochondria.

Isolated rat liver mitochondria have been treated with the general anaesthetic propofol (2,6-diisopropylphenol, 200 microM) and the physiological NO donor nitrosoglutathione (GSNO, 200 or 250 microM). The efficiency of the oxidative phosphorylation has been evaluated by measuring the respiration and ATP synthesis rates and the behavior of transmembrane electrical potential. In mitochondria energized by succinate, the simultaneous presence of both propofol and GSNO gives rise to a synergic action in affecting the resting and the ADP-stimulated respiration, the respiratory control ratio, the ATP synthesis, and the formation and utilization of the electrochemical transmembrane potential.

[Thromboembolic prophylaxis and central blocks]. / Profilassi tromboembolica e blocchi centrali.

Epidural and spinal blocks are widely used in several surgical settings in order to obtain analgesic advantages and reduce blood loss and thromboembolic complications. However, many high risk patients receive perioperatively some anti-coagulant treatments for preventing venous thrombosis and pulmonary embolism. Although a number of large observations has demonstrated a very low rate of major neurological impairment due to spinal haematomas, in the last years an increasing number of case reports seems to cause an excessive anxiety to the anaesthesiologists. On the other hand, spinal haematomas occurred in same cases without anti-coagulant therapy. An other question concerns the onset time from an epidural/spinal puncture and the development of neurological symptoms of spinal compression, which may appear even after days or weeks. Female gender, aged patients, vascular surgery, uncontrolled positions on the table, number of spinal punctures, large gauge of needle and low degree of skill are the main factors involving in the haemorrhagic phenomena around spinal cord. Accurate anamnesis, no anti-coagulant medication before surgery, and a perfect technique of managing spinal/epidural block are essential elements for reducing probability of severe bleeding and consequent expansive haematomas. Also, informed consent of patients and careful judgement of advantages vs risks of a central block for every high risk case determine the final decision about the regional anaesthesia: to do or not to do.

[Comparison of manual infusion of propofol and target-controlled infusion: effectiveness, safety and acceptability]. / Confronto tra l'infusione manuale di propofol e l'infusione a target controllato: efficacia, sicurezza ed accettabilità.

BACKGROUND: Diprifusor TCI is a newly developed target-controlled system for the infusion of propofol. Purpose of this study is to evaluate the acceptability, efficacy and safety of Diprifusor TCI in comparison with the manually controlled technique. METHODS: This multicentre, randomised, parallel group study was carried out in 160 patients undergoing surgical procedures of 10 min to 4 h duration in 8 centres. In each centre 20 male or female patients, aged > or = 18 years, ASA I-III were randomised to treatment with either Diprifusor TCI (TCI group--80 patients) or manually controlled infusion (MI group--80 patients). Assessments included hemodynamics; adverse events, including accidents, actual or possible; recovery times; anesthetist ratings of quality of induction and maintenance, and of ease of control and use of technique. Ratings were summed up in a global quality score (study end-point). RESULTS: Induction doses were significantly lower (median values 1.4 vs 1.9 mg/kg) and maintenance infusion rate significantly higher (median values 10.2 vs 8.8 mg/kg/h) in the TCI group; anesthetists ratings obtained maximum scores in most patients of either group, but more frequently in the TCI group, with significant differences for ease of control (good 91.2% TCI vs 74.7% IM; adequate 8.8 vs 21.5%; poor 0 vs 3.8%), and of use of technique (good 91.2% TCI vs 60.8% IM; adequate 8.8 vs 39.2%); the global quality score showed a significant advantage for the TCI system (median value 12 vs 11). CONCLUSIONS: The TCI technique is effective and safe, and has a better acceptability than the manually controlled infusion technique.

Effect of 2,6-diisopropylphenol and halogenated anesthetics on tetraphenylphosphonium uptake by rat brain synaptosomes: determination of membrane potential.

The effect of 2,6-diisopropylphenol (propofol) in comparison to that of the halogenated anesthetics enflurane, isoflurane, and halothane on tetrapenylphosphonium uptake by rat brain synaptosomes was studied. A direct method to separately measure the synaptosomal and the mitochondrial transmembrane potential by using the tetraphenylphosphonium cation (TPP+) was utilized. The latter is a lipophylic charged molecule which distributes between two compartments according to the transmembrane electrical potential in the presence or absence of 60 mM KCl as a synaptosomal membrane depolarizing agent. After previously reporting the damages induced by general anesthetics on isolated mitochondria, the aim of this paper was to study their possible action on the synaptosomal membrane potential and whether or not drugs concentrations damaging isolated mitochondria are also effective on synaptosomal mitochondria. The results indicated that, in the presence of glucose, mitochondria included in synaptosomes were able to maintain a transmembrane potential of 202+/-8 mV (mean +/- SD) while the synaptosomal membrane showed a potential of 78+/-8 mV (mean +/- SD). When anesthetic concentrations (0.6-1 mM propofol, 10-40 microM enflurane, 30-50 microM isoflurane, 8-15 microM halothane) that impair mitochondrial energy metabolism were used, the synaptosomal transmembrane potential was maintained and, in addition, a slight increase of the TPP+ taken up was observed as the anesthetic concentration was increased.

Mitochondrial effects of L-ropivacaine, a new local anesthetic.

The effects of the local anesthetics ropivacaine and bupivacaine were investigated on isolated rat liver mitochondria. The efficiency of oxidative phosphorylation was evaluated by measuring the rates of respiration and ATP synthesis and the magnitude of the transmembrane electrical potential (deltapsi). Bupivacaine did not alter the ADP-stimulated respiration but strongly affected the resting respiration, which was more than doubled at 0.6 mM. In addition, it decreased the transmembrane electrical potential, and the ATP synthesis rate (deltapsi was less than 100 mV at 0.6 mM). Ropivacaine did not alter the ADP-stimulated respiration, and the resting respiration seemed to be substantially unaffected up to 1.2 mM; a slight increase was observed at 1.8 and 2.4 mM. The transmembrane potential was decreased by anesthetic concentrations higher than 1.2 mM and ATP synthesis was consequently affected. The findings suggest that ropivacaine is less toxic than bupivacaine, in rat liver mitochondria.

Effect of the intravenous anesthetic 2,6-diisopropylphenol on respiration and energy production by rat brain synaptosomes.

The sensitivity of the mitochondrial energy production system to propofol (DPP) has been investigated in rat brain synaptosomes. DPP at 0.8 mM concentration produced a partial inhibition of coupled respiration, an apparent decrease of the oxygen uptake stimulation induced by CCCP and a full inhibition of the mitochondrial ATP production by synaptosomes. Higher concentrations of DPP (1 mM) fully abolish uncoupler-dependent stimulation and at 1.3 mM DPP also coupled respiration is completely blocked. Similar results were obtained when dinitrophenol replaced CCCP and phenol or propylbenzene replaced DPP. The presence of the alkyl residues seems critical for the DPP effect. In the presence of 30 mM glutamate both respiration and ATP production are enhanced but DPP effects are similar to those obtained in the absence of glutamate.

Multiple and various anaesthetics, ketamine included, in a young patient with familial dysautonomia, Case report.

A case report is presented of a 16-year-old patient who had undergone 16 general anaesthetics by different anaesthesists and under various anaesthetic techniques for dental, endoscopic, orthopaedic and ophthalmic surgical procedures over a period of 14 years. Use of ketamine, especially in an ambulatory setting, was found more suitable in terms of cardiovascular stability, safety and patient preference.

Influence of the anesthetic 2,6-diisopropylphenol (propofol) on isolated rat heart mitochondria.

The influence of the anesthetic 2,6-diisopropylphenol on isolated rat heart mitochondria has been investigated at a range of concentrations encompassing high and low clinical values. Low clinical concentrations of the anesthetic appeared unable to affect both oxidative phosphorylation and calcium homeostasis. 2,6-diisopropylphenol at high clinical levels decreased both the transmembrane electrical potential and the synthesis of ATP, while leaving mitochondrial calcium homeostasis unaffected. The results obtained suggest that isolated heart mitochondria are substantially insensitive to low clinical concentrations of 2,6-diisopropylphenol, thus largely excluding the possibility that mitochondrial alterations might be involved in the cardiac depression induced by this anesthetic.

Alteration of mitochondrial bioenergetics due to intravenous injection of a perfluorocarbon emulsion.

Wistar albino rats were intravenously injected with 1 ml of an oxyphoretic emulsion of perfluorobutyl-furane and killed 3, 7 or 30 days later. Mitochondria isolated from the liver and kidneys of treated rats showed a small decrease in the transmembrane electrical potential and a substantial depression of the rates of both ATP synthesis and ADP-stimulated respiration. These alterations in mitochondrial oxidative phosphorylation appear to be induced by perfluorocarbon and/or tensioactive molecules interacting with hydrophobic cell structures.

Long-term nasal intermittent positive pressure ventilation in advanced Duchenne's muscular dystrophy.

The aim of our study was to evaluate the long-term effect of nasal ventilation in patients with advanced Duchenne's muscular dystrophy (DMD). To this end, we compared the clinical and pulmonary function course of five subjects affected with chronic ventilatory failure due to DMD and treated with nasal intermittent positive pressure ventilation (NIPPV) with that of an unventilated comparison group; the latter consisted of another five patients with DMD, with a similar degree of clinical and respiratory functional impairment, who refused long-term mechanical ventilation. The duration of the follow-up was 24 months. At the conclusion of the trial, all patients treated with NIPPV were still alive; in contrast, four of five patients who underwent simple conservative treatment had already died (mean survival, 9.7 +/- 5.8 months). After 6 months of follow-up, mean loss of FVC and maximal voluntary ventilation was considerably higher in nonventilated subjects (respectively: -0.23 L vs +0.03 L and -5 L/min vs -1.5 L/min). These are the first comparative results confirming that long-term NIPPV helps to stabilize pulmonary function and to prolong the expectancy of life of patients with DMD.

Effects of diltiazem on liver mitochondria of rats: a reconsideration.

1. The effects of the Ca-channel blocker diltiazem (a drug of the benzothiazepine family) on bioenergetic metabolism have been assessed on isolated rat liver mitochondria. 2. Millimolar concentrations of diltiazem induced a decrease of both the ADP- and the uncoupler-stimulated respiration and a concomitant slight increase of the resting respiration. 3. Under the same experimental conditions diltiazem decreased the transmembrane electrical potential while leaving calcium uptake unaffected. 4. Micromolar concentrations of diltiazem, which are close to therapeutic haematic levels, were without effect.

Biochemical and morphological observations on rat liver and kidneys six months after intravenous injection of a perfluorocompound emulsion.

The histological appearance of liver and kidneys and the energy metabolism of isolated liver and kidney mitochondria were evaluated in rats 6 months after intravenous administration of 1 ml of a perfluorocompound emulsion. Both liver and kidney specimens showed neither significant histological alteration nor the presence of intracytoplasmic perfluorocompound particles. A substantial depression of the rate of ATP synthesis was observed both in liver and kidney isolated mitochondria (with respect to control mitochondria) although the magnitude of the transmembrane electrical potential was unaltered. The depression of ATP synthesis in mitochondria isolated from perfluorocompound-treated rats appeared then unrelated to the presence of perfluorocompound micelles within the cells, and might result from the interaction of either the perfluorocompound or the emulsifying agent with the mitochondrial ATP synthetase.

Interaction between thiopentone and subhypnotic doses of ketamine.

The hypnotic effects of thiopentone and ketamine were studied in ASA Grade I female patients aged 20-30 without premedication. The dose-response curves of ketamine 0.4 mg kg-1 and thiopentone following ketamine 0.4 mg kg-1 were determined by probit analysis. The interaction between ketamine and thiopentone was found to be an antagonistic one. This effect can be interpreted as a consequence of the different neurophysiological spectra of action of the two drugs.

Differential lung ventilation with a double-lumen tracheostomy tube in unilateral refractory atelectasis.

Two patients with refractory hypoxemia due to unilateral lung atelectasis were treated with differential lung ventilation (DLV) through a Robertshaw-type, double-lumen tracheostomy tube. DLV was applied using two non-synchronized ventilators and maintained for 6 and 3 days, respectively. Ventilator settings were chosen in accord to the clinical, laboratory and chest X-rays results. Particularly, tidal volume and PEEP were set to avoid excessively high alveolar pressure and to obtain the highest possible value of compliance. We investigated the mechanical properties of the two lungs separately by measuring airway pressure and compliance of each lung before the beginning of DLV and at 0, 5, 24, and 48 h after. Initially we observed in both patients very low values of compliance (7-9 cm H2O/l) and a significant level of PEEPi (12-8 cm H2O) of the diseased lung, whereas PEEPi in the healthy lung was negligible. The clinical improvement was assessed by sequential chest X-rays and by significant improvement of arterial blood gas and PaO2/FiO2 ratios and was associated with a progressive increase of compliance (24-22 cm H2O/l) and by a fall of PEEPi levels (5-4 cm H2O) of the diseased lung. We also observed an improvement of SvO2, O2AVI, PVRI and Qva/Qt values (Case 1). The tracheostomy tube used to apply DLV was very reliable, allowing easy nursing care and selective bronchial aspirations. We conclude that DLV is a very useful technique in unilateral lung pathology, and it can be a life saving procedure in selected patients, by supplying volume and PEEP more efficiently to the affected lung.

Uncoupling effect of the general anesthetic 2,6-diisopropylphenol in isolated rat liver mitochondria.

2,6-Diisopropylphenol, a general anesthetic, was previously reported to reduce the transmembrane electrical potential in isolated rat liver mitochondria without affecting the rate of ATP production. This effect appeared to contrast with the generally accepted chemiosmotic mechanism for oxidative phosphorylation. In this study we further examined the influence of 2,6-diisopropylphenol on the production of ATP by isolated mitochondria and we studied its effect on the permeability of the inner mitochondrial membrane to protons. In order to clarify the effects of 2,6-diisopropylphenol on mitochondrial ATP production the activities of the adenine nucleotide translocator and the ATP synthetase were evaluated. The results obtained indicate that the depression of the transmembrane electrical potential elicited by 2,6-diisopropylphenol decreased the activity of the ATP synthetase (as expected in the chemiosmotic model for energy coupling), but not that of the adenine nucleotide translocator. The decrease of the ATP synthetase activity, however, did not result in an apparent inhibition of the overall rate of ATP production in isolated mitochondria due to the rate-limiting effect of the adenine nucleotide translocator in this process. Moreover 2,6-diisopropylphenol was found to increase the permeability to protons of the inner mitochondrial membrane; this effect became more marked as the pH of the incubation medium was increased, demonstrating that it involved the dissociated form of 2,6-diisopropylphenol. These observations suggested that 2,6-diisopropylphenol affected oxidative phosphorylation by acting as a mild protonophore and that its effectiveness was limited by the low fraction of phenol dissociated at near-physiological pH.