1. We have determined the ventilatory response to CO2 at two levels of end-tidal O2 tension in eight normal subjects before and after (1) 4 days of 0.242 mmol (80 mg) oral frusemide daily and (2) 4 days of 0.024 mmol (10 mg) bendrofluazide daily.

2. Frusemide produced no significant alkalosis, change in end-tidal CO2 tension or alteration in the CO2 response line. However, we did demonstrate a linear relationship between the change in plasma total CO2 content and the change in intercept of the CO2 response line in hyperoxia after frusemide.

3. Bendrofluazide produced a metabolic alkalosis with no significant change in end-tidal CO2 tension. The CO2 response line after the drug showed a decrease in slope in hyperoxia and a shift to the right of the intercept in hypoxia. There was no relationship between change in plasma total CO2 content and change in the intercept of the CO2 response line in hyperoxia.

4. If these results obtained on normal subjects are applicable to patients with chronic bronchitis and emphysema, frusemide might be the diuretic of choice for use with controlled oxygen therapy in the management of acute exacerbations of this disease when it is complicated by ventilatory failure.

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