Repeated Exposure to Rapidly Developing Hypoxemia Influences the Interaction between Oxygen and Carbon Dioxide in Initiating Arousal from Sleep in Lambs

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Abstract
Experiments were done on 12 lambs to determine if repeated exposure to hypoxemia influences the interaction between oxygen and carbon dioxide in causing arousal response from sleep. Each lamb was anesthetized and instrumented for sleep staging and measurements of arterial Hb oxygen saturation. No sooner than 3 days after surgery, measurements were made in quiet and active sleep during control periods when the lambs were breathing 21% oxygen and during experimental periods when the lambs were breathing either 5% O2-0% CO2, 5% O2-5% CO2 or 5% O2-10% CO2. Each experimental period was terminated during each epoch by changing the inspired gas mixture back to 21% oxygen once the animal aroused from sleep. The lambs were divided into two groups. One group (n = 7) was studied without prior exposure to hypoxemia and the other group (n = 5) was studied after exposure to 5% oxygen during ∼100 epochs of sleep until they aroused. In lambs not previously exposed to hypoxemia, there was evidence for a slight interaction between oxygen and carbon dioxide in initiating arousal but only from quiet sleep. Repeated exposure to hypoxemia resulted in an arousal response decrement to hypoxemia. In lambs previously exposed to hypoxemia, there was evidence for an interaction between oxygen and carbon dioxide in initiating arousal from both quiet and active sleep (i.e. the time to arousal decreased and the saturation at arousal increased as increasing amounts of carbon dioxide were added to the hypoxic gas mixture). Thus, our data provide evidence that a greater interaction exists between oxygen and carbon dioxide in initiating arousal—particularly in active sleep—once an arousal response decrement has developed to hypoxemia alone.