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Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106
Long-term
facilitation (LTF) of breathing elicited by episodic hypoxia (EH) is an
extensively studied example of plasticity of respiratory motor
behavior. Previous studies employed the paradigm of EH wherein each
episode of hypoxia was 5 min. This paradigm is rarely encountered in
nature. Brief episodes of hypoxia are encountered frequently with
recurrent apneas, wherein hypoxic episodes last a few seconds only.
Recent studies suggest that chronic intermittent hypoxia (CIH)
represents a form of oxidative stress involving reactive O2
species. The objectives of the present study were to determine
1) whether acute, repeated, brief EH (15 s) elicit LTF in
breathing and 2) whether prior conditioning with CIH
modulates acute EH-induced LTF of breathing, and if so whether reactive
O2 species are involved. Experiments were performed on anesthetized, vagotomized, paralyzed, and mechanically ventilated rats,
and efferent phrenic nerve activity was monitored as an index of
respiratory motor output. In control animals, acute EH (15-s hypoxia;
10 episodes; n = 9) increased minute neural
respiration, which persisted during 60 min of the posthypoxic period,
suggesting LTF of breathing. EH-induced LTF of respiration was markedly
augmented in CIH-conditioned animals (15-s hypoxia, 9 episodes/h, 8 h/day for 10 days; n = 9). By contrast, conditioning
with a comparable, cumulative duration of sustained hypoxia (4-h
hypoxia; n = 8) did not augment LTF elicited by acute
EH. Systemic administration of manganese (III) tetrakis
(1-methyl-4-pyridyl) porphyrin pentachloride (5 mg · kg
1 · day1
for 10 days), a potent scavenger of O
episodic hypoxia; recurrent apnea; superoxide anions; long-term facilitation; respiratory motor output
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