The modulation of oxygen toxicity by intermittent exposure.

Intermittent delivery of hyperbaric O2 protects animals from pulmonary and central nervous system toxicity: more total O2 time can be tolerated if interrupted by short periods of low O2. Little is known about the mechanisms or optimization of systematically varied intermittency. Survival time was recorded in groups of 16 awake guinea pigs (239 +/- 23(SD) g) exposed to continuous O2 at 2.8 ATA or to one of six different schedules of O2 delivered with periodic air (PO2 = 0.588 ATA) interruptions. The survival curves had a lag time (11-14 hr of O2 time depending on the intermittency schedule) with a rapid loss of animals thereafter. Data were analyzed with risk models linking the probability of death to the accumulation of a putative toxic substance, X1. A model in which X1 accumulated in proportion to the PO2 and disappeared by first-order decay during periods of low O2 exposure was modified to include an effective rate constant for changes in X1: dX1/dt = a.PO2 + K1.(PO2 - Os).X1. First-order kinetics operated when PO2 was below the oxygen set point (Os), but the rate constant reversed sign to become a self-amplifying system when PO2 was above Os. This model achieved an excellent fit as judged by goodness-of-fit statistics while a simpler one did not. Our analysis suggests that the accumulation of toxicity does not correspond to a stable linear toxic process, but requires one in which a toxic process grows autocatalytically.