The effect of high helium pressure on the inherent tone of guinea pig tracheal smooth muscle

Abstract

All submariners undergo ascent training from a maximum of 100 feet of seawater (fsw). Since the training tank opened in 1954 there have been a number of serious incidents, including loss of consciousness, paralysis and death which have been attributed to pulmonary air embolism. Work on isolated tissues in the 1930's suggested that voluntary muscle underwent a spontaneous contracture as a result of compression. It was proposed that rapid compression and/or decompression could result in bronchoconstriction, leading to airway closure and air trapping. Recently, the limit to which man can dive safely has been extended by the use of saturation diving. Some divers have reported sensations of breathlessness during exercise while at depth under saturation conditions. Thus, bronchoconstriction may also occur under static, high pressure conditions. The guinea pig tracheal chain has been used as a model for human airway smooth muscle, since both have inherent tone in vitro. This preparation was studied at atmospheric pressure to establish its characteristic features with respect to nerve population, receptor population and the mechanism by which tone is initiated and maintained. Particular attention was paid to the response of the tissue to hypoxia. Some preliminary hyperbaric experiments revealed the importance of controlling other variables known to affect tracheal smooth muscle function such as P02, PC02 and p11. Helium gas was shown to be non-toxic at 1 bar and was used as compression gas in the majority of experiments. Tracheal smooth muscle responded to compression with a relaxation. Neither receptor blocking drugs, nor the neurotoxin Tetrodotoxin (TTX) had any effect on this response. A 3-fold increase in calcium concentration of the bath fluid reduced but did not abolish the response to compression. Quinidine and ouabain, two agents known to cause intracellular Ca2+ to rise, were also tested for their effect on the response to compression. Both quinidine and ouabain caused inherent tone to rise. However, neither drug significantly reduced the response to compression. The effect of pressure on the response to field stimulation was also investigated. When expressed as a percentage of the tone at the time of stimulation, the response was not significantly reduced, even at 67 bar. This can be contrasted with the effect of hypoxia on the response to field stimulation where, followinga similar decrease in tone, the response was significantly reduced. The effect of pressure is discussed with reference to the results of the experiments performed at atmospheric pressure. Tracheal smooth muscle does not contract in response to compression and the hypothesis is refuted. The possible implications of the results of this study for submarine escape training and saturation diving are discussed.

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