General anesthesia can be caused by various, chemically very different molecules, while several other molecules, many of which are structurally rather similar to them, do not exhibit anesthetic effects at all. To understand the origin of this difference and shed some light on the molecular mechanism of general anesthesia, we report here molecular dynamics simulations of the neat dipalmitoylphosphatidylcholine (DPPC) membrane as well as DPPC membranes containing the anesthetics diethyl ether and chloroform and the structurally similar non-anesthetics n-pentane and carbon tetrachloride, respectively. To also account for the pressure reversal of anesthesia, these simulations are performed both at 1 bar and at 600 bar. Our results indicate that all solutes considered prefer to stay both in the middle of the membrane and close to the boundary of the hydrocarbon domain, at the vicinity of the crowded region of the polar headgroups. However, this latter preference is considerably stronger for the (weakly polar) anesthetics than for the (apolar) non-anesthetics. Anesthetics staying in this outer preferred position increase the lateral separation between the lipid molecules, giving rise to a decrease of the lateral density. The lower lateral density leads to an increased mobility of the DPPC molecules, a decreased order of their tails, an increase of the free volume around this outer preferred position, and a decrease of the lateral pressure at the hydrocarbon side of the apolar/polar interface, a change that might well be in a causal relation with the occurrence of the anesthetic effect. All these changes are clearly reverted by the increase of pressure. Furthermore, non-anesthetics occur in this outer preferred position in a considerably smaller concentration and hence either induce such changes in a much weaker form or do not induce them at all.

• MeSH
• 1,2-dipalmitoylfosfatidylcholin chemie   MeSH
• anestetika celková * farmakologie   MeSH
• anestezie * MeSH
• chloroform chemie   MeSH
• lipidové dvojvrstvy chemie   MeSH
• membrány MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,2-dipalmitoylfosfatidylcholin MeSH
• anestetika celková * MeSH
• chloroform MeSH
• lipidové dvojvrstvy MeSH

BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).

• MeSH
• anestetika celková farmakologie   MeSH
• anestetika intravenózní MeSH
• aplikace inhalační MeSH
• celková anestezie MeSH
• elektivní chirurgické výkony MeSH
• intravenózní anestezie * MeSH
• jednoduchá slepá metoda MeSH
• Kaplanův-Meierův odhad MeSH
• koronární bypass * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita MeSH
• nemoci koronárních tepen mortalita   patofyziologie   chirurgie   MeSH
• senioři MeSH
• tepový objem MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• pragmatická klinická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• anestetika celková MeSH
• anestetika intravenózní MeSH

The aim of study was to review the status of arterial pH, pO(2) and pCO(2) under general anesthesias in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using three- to four-month-old pentobarbital(P)-, ketamine/xylazine(K/X)- and zoletil(Z)-anesthetized female Wistar rats after a four-week adaptation to an LD cycle (12 h light:12 h dark). The animals were divided into three experimental groups according to the anesthetic agent used: P (light n=11; dark n=8); K/X (light n=13; dark n=11); and Z (light n=18; dark n=26). pH and blood gases from arterial blood were analyzed. In P anesthesia, LD differences in pH, pO(2), and pCO(2) were eliminated. In K/X anesthesia, parameters showed significant LD differences. In Z anesthesia, LD differences were detected for pH and pO(2) only. Acidosis, hypoxia, and hypercapnia have been reported for all types of anesthesia during the light period. In the dark period, except for P anesthesia, the environment was more stable and values fluctuated within normal ranges. From a chronobiological perspective, P anesthesia was not the most appropriate type of anesthesia in these rat experiments. It eliminated LD differences, and also produced a more acidic environment and more pronounced hypercapnia than K/X and Z anesthesias.

• MeSH
• analýza krevních plynů metody   MeSH
• anestetika celková škodlivé účinky   krev   farmakologie   MeSH
• celková anestezie * škodlivé účinky   trendy   MeSH
• chronobiologické jevy účinky léků   fyziologie   MeSH
• fixní kombinace léků MeSH
• hyperkapnie krev   chemicky indukované   MeSH
• hypoxie krev   chemicky indukované   MeSH
• ketamin škodlivé účinky   farmakologie   MeSH
• krysa rodu Rattus MeSH
• pentobarbital škodlivé účinky   farmakologie   MeSH
• potkani Wistar MeSH
• tiletamin škodlivé účinky   farmakologie   MeSH
• zolazepam škodlivé účinky   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• anestetika celková MeSH
• fixní kombinace léků MeSH
• ketamin MeSH
• pentobarbital MeSH
• tiletamin MeSH
• tiletamine, zolazepam drug combination MeSH Prohlížeč
• zolazepam MeSH

BACKGROUND: Surface electrogastrography (EGG) is a non-invasive method for clinical assessment of gastric myoelectrical activity. Different forms of general anaesthesia might have various effects on porcine EGG. The aim of this study was to evaluate the impact of different anaesthetic agents on EGG in experimental pigs. METHODS: Four 15-minute EGG intervals were recorded and analysed. A baseline EGG recording was started 20 minutes after intramuscular injection of ketamine and azaperone (periods A and B). Four different regimens of general anaesthesia followed immediately after the baseline EGG (5 pigs in each experimental group): thiopental, isoflurane, nitrous oxide and isoflurane plus nitrous oxide. EGG recordings followed for the next 30 minutes under general anaesthesia (periods C and D). The dominant frequencies of slow waves were compared between the baseline intervals A and B and periods C and D under general anaesthesia. RESULTS: The mean dominant frequency was within the normal range (2.3 - 3.5 cycles per minute) in all animals in all regimens. Thiopental general anaesthesia did not influence any change of the dominant frequency of slow waves. Nitrous oxide general anaesthesia increased the dominant frequency of slow waves in a statistically significant manner (baseline: 2.93 ± 0.53 and 3.01 ± 0.53; under general anaesthesia: 3.25 ± 0.34 and 3.29 ± 0.38 cycles per minute; p < 0.001, p = 0.003, p < 0.001, p < 0.001). Nitrous oxide together with isoflurane induced a statistically significant decrease of dominant frequency in the last 15-minute interval (2.66 ± 0.55 cycles per minute) compared to the baseline recording (2.81 ± 0.49; p = 0.030). CONCLUSIONS: All changes of porcine gastric myoelectric activity assessed by the dominant frequency of slow waves during EGG remained within the normal range although some of them achieved statistical significance. Thus all tested agents used for general anaesthesia can be recommended in preclinical studies with porcine models focused on gastric myoelectric activity without any risk of compromising the results. Thiopental seems to be the most suitable as it did not cause any changes at all.

• MeSH
• anestetika celková farmakologie   MeSH
• isofluran farmakologie   MeSH
• migrující myoelektrický komplex účinky léků   fyziologie   MeSH
• modely u zvířat MeSH
• oxid dusný farmakologie   MeSH
• prasata MeSH
• thiopental farmakologie   MeSH
• žaludek účinky léků   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anestetika celková MeSH
• isofluran MeSH
• oxid dusný MeSH
• thiopental MeSH