Molecular dynamics simulation study of the effect of halothane on mixed DPPC/DPPE phospholipid membranes.

We report results of a molecular dynamics simulation study of the effect of one general anesthetic, halothane, on some properties of mixed DPPC/DPPE phospholipid membranes. This is a suitable model for the study of simple, two-phospholipid membrane systems. From the simulation runs, we determined several membrane properties for five different molecular proportions of DPPC/DPPE. The effect of halothane on the studied membrane properties (area per lipid molecule, density of membrane, order parameter, etc.) was rather small. The distribution of halothane is not uniform through the bilayer thickness. Instead, there is a maximum of anesthetic concentration around 1.2 nm from the center of the membrane. The anesthetic molecule is located close to the phospholipid headgroups. The position of the halothane density maximum depends slightly on the DPPC/DPPE molar proportion. Snapshots taken over the plane of the membrane, as well as calculated two-dimensional radial distribution functions show that the anesthetic has no preference for either phospholipid (DPPC or DPPE). Our results indicate that this anesthetic molecule has only small effects on DPPC/DPPE mixed membranes. In addition, halothane displays no preferential location around DPPC or DPPE. This is probably due to the hydrophobic nature of halothane and to the fact that the chosen phospholipids have the same hydrophobic tails.

Kinetics of dissolution of gaseous halothane in Krebs-Ringer's solution.

The responses of biological tissues to volatile anaesthetics are commonly studied by incubating specimens in a bath containing dissolved anaesthetic. One accepted technique is to bubble an anaesthetic gas into several incubation chambers simultaneously. To assess the validity of this technique in producing dissolved anaesthetic (the biologically active form) at equal rates among the several chambers, we determined the kinetics of dissolution of halothane gas in three tissue incubation chambers containing Krebs-Ringer's solution. We found that (1) the dissolution kinetics were first-order in all three chambers; (2) the rate of halothane dissolution depended on the gas bubbling rate; (3) even with the same bubbling rates, chamber shapes and chamber volumes, the dissolution rates for the three chambers were not equal, suggesting that dissolution rate depended on small differences in chamber geometry; (4) the dissolution rates could be made equal by adjusting chamber bubbling rates according to calculations involving the first-order rate equation; and (5) the maximum coefficient of variation of dissolved halothane concentration was 9% at 63% approach to equilibrium and 3% at equilibrium.