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By J. F. Nunn

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In the control of breathing. F. of elevated P c o 2 and reduced pH. Leusen's work touched off a long series of studies aimed at localizing central chemoreceptors. F. could influence the respiratory neurones within the substance of the medulla in the short time required for development of the ventilatory response to inhaled carbon dioxide. These studies were carried out mainly in the University of Göttingen (Loeschcke and Keopchen) and the University of California, San Francisco (Mitchell and Severinghaus), although various combinations of many authors appeared in numerous publications which included joint work between members of the two universities.

However, in breath holding, movement is prevented by closure of the glottis and there is an 'inappropriateness' between the muscle activity and the (lack of) movement which results. This accords with the idea of ' inappropriateness' advanced as a general hypothesis to explain the sensation of dyspnoea (Campbell and Howell, 1963). The discomfort of breath holding would then be regarded as an extreme form of inappropriateness, differing only quantitatively from that of mechanically hindered breathing.

Determination of the effect of a drug on the response curve is far more informative than simple measurements of ventilation or P c o 2, without regard to the interaction of these two variables. For example, decrease in ventilation may simply reflect a decrease in metabolic rate without any true depression of breathing. Although there are minor differences with individual drugs, those which are stimulant to ventilation cause a displacement to the left with a steepening of slope. The effect is thus broadly similar to that of hypoxia (Figure 7) and it is therefore important that: measurements of the effect of a drug be made when hypoxic drive is minimal as, for example, when the arterial P o 2 is in excess of say 150 mm Hg.

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