THE METABOLIC EFFECTS OF ANAESTHESIA anaesthesia. Their importance lies in the fact that they may impair the ability of tissue to metabolize normally and so function normally. The effect of anaesthetics on insulin activity has not been fully evaluated, the only agent studied being ether. Ether does not appear to affect the action of insulin3' 1. References 1. 2. 3. 4. 5. 6. 7. 8. 9. BRUNNER, E. A. (1969) Anesthesiology 30, 24. COHEN, P. J., and MARSHALL, B. E. (1968) Toxicity of Anesthetics, edit. Fink, B.R. Baltimore, Williams and Wilkins Co., p. 24. GREENE, N. M. (1963) Inhalation Anesthetics and Carbohydrate Metabolism. Baltimore, Williams and Wilkins, pp. 51-54. GREENE, N. M. (1965) Anesthesiology, 26, 731. GREENE, N. M., and CERVENKO, F. W. (1967) Acta anaesth. scand. Suppl. 28. GREENE, N. M., and WEBB, S. R. (1969) Anesthesiology, 31, 548. PARADISE, R. R., and Ko, K. C. (1970) Anesthesiology, 32, 124. SCHWEIZER, O., et al. (1967) Anesthesiology, 28, 814. WILLIAMS, T. F., et al. (1968) Amer. J. Physiol. 215, 1200. THE EFFECT OF TEMPERATURE CHANGES ON THE CELL MEMBRANE Dr. P. J. Goodford THIE PROPERTIES OF cell membranes depend upon their structure; their environment; their metabolism and their permeability, and it is necessary to consider the effects of temperature changes upon each of these factors. The general effect of cooling is to slow down all the molecular processes because molecules have less energy at low temperatures, and warming has the opposite effect which may be measured as a Qlo. For example, when a gas is warmed from 270 C. to 370 C. at constant volume, its pressure increases proportionately to the absolute temperature 3100A change: - 1.033; and the Qlo is 1.033. This is a typical value 3000A for a simple physical change, although diffusion mechanisms are more temperature-sensitive: the diffusion coefficient for NaCl in water rises from 1.39 x 10-5 cm.2/sec. at 20° C. to 1.84 x 10-5 cm.2/sec. at 300 C. (International Critical Tables) giving a Qlo of 1.32. Chemical reactions, enzyme-catalysed processes and metabolic pathways are more sensitive to warming, and in some cases there may be a ten-fold increase of reaction rate when the temperature rises 10° C. (Qio= 10). The normal bodily functions are accurately balanced at 370 C. They will not in general be balanced at any other temperature because each function has its own Qlo value. Some effects of the imbalance occur more rapidly and to a greater extent than others, and these processes are most significant during hypothermia. It is thought that changes of membrane structure are relatively slow to occur. Cell membranes separate regions of different chemical composition, and there are concentration gradients across the membranes. The environment is inherently unstable with relatively dilute intracellular 70 THE METABOLIC EFFECTS OF ANAESTHESIA sodium and calcium, and concentrated intracellular potassium. The ' sodium pump' maintains these gradients, and the ions tend to diffuse across the cell membrane when this metabolic pump is slowed by cooling. However, the actual change in cytoplasmic concentrations will depend upon the size of the cells, small cells being most affected because they have a large ratio of surface area to volume. A temporary metabolic blockade may not change the concentrations appreciably, and the body is partially protected in this way from some effects of brief cooling. Hypothermia rapidly changes the permeability of cell membranes. The effect is greater than one might expect for a physical process, because permeability is analogous to diffusion which has a relatively high Qlo. Excitability is immediately affected since it depends on ionic permeabilities, and a new pseudo-steady state should be established quickly with properties depending on the new temperature. However, these properties will in fact change as the metabolic blockade slowly alters the environment. One may conclude that temperature changes disturb the equilibrium of the cell membrane in different ways which interact and compete with each other. At some temperatures these interactions may nearly cancel out for a time, and these are the conditions which should be optimal for hypothermia. USE OF TRACER TECHNIQUES IN THE STUDY OF ANAESTHETIC DISTRIBUTION AND METABOLISM Professor E. N. Cohen THE IMPORTANCE OF radioisotopes in biological research is well established, and a number of methods are used to incorporate radioactivity into biologically active compounds. These include chemical synthesis, biological synthesis, and activation analysis. Selection of the proper isotope is critical and is dependent upon the energy characteristics of the radiation, the half-life of the isotope, and the specific activity that can be incorporated into the molecule. Detection of the radiation present may be accomplished through use of the ionization chamber, Geiger counter, scintillation counter, or by means of radioautography. The latter approach offers special benefit for the study of anaesthetic drugs. Ullberg's whole body autoradiographic technique provides an added advantage by permitting the use of water-soluble compounds and a simultaneous scan of the entire organism. Whole-body autoradiographic studies with the muscle relaxants have been made possible through incorporation of a tritium label. The muscle relaxants distribute rapidly throughout the body water compartments, but their relative lipid insolubility prevents entrance into the stomach and affords both a blood brain and a placental barrier. High 71