1. The effect of breathing an anaesthetic aerosol of 5% bupivacaine hydrochloride has been assessed in dog and man. 2. In the dog, the cough reflex was abolished and the Hering-Breuer inflation reflex severely impaired or abolished; breathing became slower and deeper; no pathological changes were found in the lungs of these dogs. 3. In man, no untoward effects resulted from a 10 min period of aerosol inhalation; there were no systematic effects on airway resistance or lung volumes and the cough reflex in response to either tactile or chemical (citric acid aerosol) stimulation was invariably abolished. The Hering-Breuer inflation reflex was impaired, but this was not associated with any change in resting ventilation. The Ve/CO2 response was enhanced after aerosol anaesthesia; subjects felt an exaggerated dyspnoea. The aerosol anaesthesia abolished the afferent pathway of a reflexly elicited bronchoconstriction in one subject. There was no effect on the ability to hold the breath, or on the quality of the associated sensation. 4. Control aerosols of sodium chloride solution or phosphate buffer produced no effects. Control experiments with intravenous infusions of bupivacaine proved that none of the effects could have been produced by systemic effects of the absorbed anaesthetic. 5. Plasma concentrations of bupivacaine in man did not exceed a recognized toxic level. The experiments demonstrate a safe reversible anaesthesia of the airways in man lasting for a period of 10-20 min.

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SUMMARY1. The ventilatory response to electrically induced 'exercise' was studied in six chloralose-anaesthetized dogs. The on-transient and steady-state responses to ' exercise' were compared in the same dogs before and after spinal cord transaction at T8/9 (dermatome level T6/7) on fifteen occasions.2. Phasic hind limb 'exercise' was induced for periods of 4 min by passing current (2 Hz modulated 50 Hz sine wave) between two needles inserted through the hamstring muscles. The maximum current used was 30 mA. This was below the level previously found to produce an artifactual stimulation of breathing with the cord intact.3. Cord transaction produced no significant change in either the resting values of ventilation (PI) and CO2 production (fco2) or the ventilatory equivalent for CO2 during 'exercise' (A Vj/A TCo2) 4. During the steady state ofexercise Pa Co2 was on average significantly lower than at rest with the cord intact (mean AIa, co2, -2-1 mmHg; range-57 to +1), and higher, though not significantly, with the cord cut (mean Pa Co,, + 1-2 mmHg; range -1-5 to + 4-3). However, even in the absence of spinal cord transmission, the ventilatory response to exercise could not be accounted for on the basis ofCO2 sensitivity; the A P/API,CO2 obtained with exercise (apparent sensitivity) was significantly greater than that obtained with CO2 inhalation (true sensitivity) both before and after cord section.5. V, and PcoC increased more slowly with the cord cut than with the cord intact.This was thought to be due to a slower increase in venous return in the absence of sympathetic innervation of the lower half of the body following cord transaction.6. Similar experiments were performed during muscle paralysis (following gallamine triethiodide). Ventilation was maintained with a respirator controlled by phrenic nerve activity. These experiments showed an increase in ventilation, independent of muscle contraction, which was only present when the cord was intact and which was confined to the on-transient. Only in the absence of spinal cord transmission could

SUMMA31RY1. The inhalation of CO2 produces a tachypnoea only in the presence of intact vagus nerves; the present study was designed to examine the mechanism of this phenomenon in the dog.2. Closed-chest cardiopulmonary bypass was established in dogs weighing [16][17][18][19][20][21][22][23][24] kg, anaesthetized with chloralose. When the 'bypass' was established pulmonary blood flow ceased, PA Col was reduced and the respiratory rate slowed. 3-10 % CO2 in 02 could then be inhaled without change in the level of P ,co, set at the oxygenator.3. The addition of CO2 in these concentrations to the inspired oxygen resulted in an increase in respiratory frequency, maximal at the first breath and sustained for the 1 min period of exposure. The increase in respiratory frequency was due to a shortening of expiratory duration. Inspiratory duration did not change. The response was absent after vagotomy.4. Inert gases in 02, given as a control, had no effect on breathing.5. The effect of raising Pa cC2 (by increasing the concentration of CO2 in the gas equilibrating the blood in the oxygenator), was primarily to increase tidal volume.6. The ventilatory effect of inspiring C02/02 mixtures was shown to be additive to the effect of raising Pa, co,.7. These experiments show that an afferent vagal reflex originating from the lungs causes tachypnoea, when a dog, on 'bypass', inhales low concentrations of CO2 in 02.

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