Enhanced Phrenic Long‐Term Facilitation (pLTF) Following Repetitive Acute Intermittent Hypoxia

Abstract

Two well‐studied models of respiratory plasticity are phrenic and XII long‐term facilitation (LTF) following acute intermittent hypoxia (AIH). Since pretreatment with chronic intermittent hypoxia (72, 5 min episodes/day, 7 days) enhances LTF, we tested the hypothesis that pre‐treatment with a less severe protocol similarly enhances LTF, potentially with fewer adverse side effects. Lewis rats were exposed to repetitive AIH (3xwAIH: 10.5% O2; 10, 5min episodes/day, 3 days per week for 4 weeks) and then anaesthetized and ventilated to enable phrenic and XII nerve recordings. After baseline measurements, rats were exposed to AIH (3, 5 min episodes) to elicit LTF. 3xwAIH enhanced pLTF versus sham, normoxia treated rats (176±42% vs 55±8% baseline 60 min post‐AIH, respectively; p<0.01; n=10 per group). However, XII LTF was unaffected by 3xwAIH (99±27% vs 135±30% baseline, respectively; p>0.05; n=10 per group). Enhanced pLTF is associated with increased expression of proteins necessary for pLTF within phrenic motor neurons (Satriotomo et al., ibid) and is modulated by glycolytic flux (MacFarlane et al., ibid). Repetitive AIH may be a useful therapeutic tool to increase respiratory motor output without adverse side effects in conditions of limited ventilatory capacity, such as cervical spinal injury or neurodegenerative disease. (NIH HL69064, NS057778, HL080209 and Craig H. Neilsen Foundation).