Abstract

A method was developed for studying the effect of drugs on unanesthetized dogs, in which samples of alveolar air were automatically collected at the same time that the rate, rhythm and minute-volume of respiration were recorded.

A special study was made of caffeine on a morphinized center. The course of events is schematically as follows:

1. A preliminary period of over-ventilation lasting two to ten minutes and at times longer during which the CO₂ tension of the alveolar air falls.

2. A secondary period which starts with a low CO₂ tension and in which the tension remains low for two hours or longer though it gradually increases. The over-ventilation has largely subsided by the beginning of this period and during the remainder of it the ventilation is nearly normal.

The course of caffeine stimulation cannot be followed by the ventilation. The CO₂ tensions indicate that the effect on the respiratory center is long lasting. Repeated injections are followed by over-ventilation unless the injections are so close together that the alveolar air indicates residual stimulation from the initial one.

Alpha-lobeline stimulations following intravenous injections are very short lived but the stimulation outlasts the period of over-ventilation. In series of injections at the proper interval the effect is reproduced in each one. On the morphinized center in the dog the drug is more active than caffeine in doses which do not produce emesis or convulsions. The threshold of respiratory stimulation is associated with a rise of blood pressure. It is too active for intravenous administration but long lasting effects can be obtained by subcutaneous injections.

Pentamethylenetetrazol (Cardiazol) effectively stimulates the morphinized center. The period of over-ventilation is relatively longer with respect to the period of stimulation due to the general excitation. However, the intravenous convulsive dose is so close to the respiratory stimulant dose that convulsions were easily produced. With subcutaneous injections stimulation of the respiration without convulsions was commoner.