title: The interactions between pressure and anaesthetics.
abstract: Compression of animals causes excitation, which has recently posed a barrier to deeper diving. The broad question addressed here is how far the inert gas breathed modifies the excitatory effects of hydrostatic pressure. By using aquatic animals we first show that helium postpones the onset of pressure-induced paralysis by some 35 atm. Next we show that in mammals compressed with helium, five anaesthetic gases (nitrogen, argon, nitrous oxide, carbon tetrafluoride, sulphur hexafluoride) all elevated dose-dependently the median pressure of four distinct phases of the high pressure neurological syndrome (h.p.n.s.) (complete spasms, clonic convulsions, tonic convulsions and non-tonic death). All the gases were equally efficacious relative to their anaesthetic potency. However, the sensitivity of each phase of the h.p.n.s. to anaesthetic gases differed. Most notably, the median pressure for tonic convulsions was elevated about three times more by a given partial pressure of anaesthetic gas than were the median pressures for complete spasms or non-tonic death. These observations can be fitted remarkably well by the hypothesis that a given phase of the h.p.n.s. is activated when some hydrophobic region is compressed beyond a certain critical amount by the application of pressure. Absorption of an inert gas in this region will cause it to expand, tending to elevate the median pressure for that phase of the h.p.n.s. Our data and analysis allow the following conclusions relevant to diving practice. All gases protect against the h.p.n.s. but some phases of this complex syndrome are more effectively controlled than others. Although addition of a second inert gas to helium allows substantial increases in the pressure at which h.p.n.s. occurs, the onset of anaesthesia (or inert gas narcosis) will limit the ultimate gain. The composition of therapeutic gas mixtures becomes more narrowly defined as the pressure increases. The optimum mixture may be different for each phase of the h.p.n.s., and the order of presentation of the h.p.n.s. symptoms may be changed by the second inert gas. We may also predict that physiological sites may exist where helium acts like an anaesthetic. If such sites resulted in physiological dysfunction, addition of a second gas would exacerbate the situation.
mesh_terms: D000777:Anesthetics / Q000627:therapeutic use*; D000818:Animals; D001001:Anura; D001274:Atmospheric Pressure; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology; D004242:Diving; D004305:Dose-Response Relationship, Drug; D006371:Helium / Q000494:pharmacology; D008297:Male; D008433:Mathematics; D051379:Mice; D008815:Mice, Inbred Strains; D013577:Syndrome
chemical_list: D000777:Anesthetics; D006371:Helium