Shorter hypoxic and inter-hypoxic intervals enhance acute intermittent hypoxia-induced phrenic long-term facilitation

• Published in: Physiology (Bethesda, Md.) Md.), 2023-05, Vol.38 (S1)
• Main Authors: Burrowes, Kayla, Marciante, Alexandria, Mitchell, Gordon
• Format: Article
• Language: English
• ISSN: 1548-9213; 1548-9221
• DOI: 10.1152/physiol.2023.38.S1.5732415

Abstract only Phrenic long-term facilitation (pLTF) is a form of respiratory motor plasticity evoked by repeated exposure to low oxygen (acute intermittent hypoxia; AIH). AIH has emerged as a promising therapeutic approach to restore lost respiratory and non-respiratory function in people with spinal cord injury and other clinical disorders that compromise movement. Optimal AIH protocols ( e.g. episode severity/duration and number of hypoxic episodes) to elicit plasticity (and therapeutic benefit) have not yet been established. Three, 5-minute moderate hypoxic episodes with 5-minute intervals have been used most often to study pLTF. New data suggest that the same cumulative duration of hypoxia ( i.e. 15 min), when presented in shorter episodes, enhances pLTF by minimizing hypoxia-evoked adenosine release. Although the “standard” AIH protocol can be improved by reducing the duration of hypoxic episodes, little attention has yet been given to the duration of inter-hypoxic intervals. Thus, we began investigations concerning the impact of interval duration and episode number in moderate AIH protocols (mAIH; arterial P O2 = 40-55mmHg). pLTF was assessed in anesthetized, paralyzed, vagotomized and ventilated male Sprague-Dawley rats exposed to mAIH consisting of: 1) 3, 1 minute hypoxic episodes (3x1) with either 5-, 2- or 1-minute inter-hypoxic intervals; or 2) 2, 5-minute hypoxic episodes with a single 15-minute interval, compared with the conventional protocol (3, 5 minute hypoxic episodes, 5 minute intervals). mAIH consisting of 3x1, 5-min intervals elicit similar pLTF versus 3, 5 min episodes with 5-min intervals (64 ± 7% and 64% ± 1%, respectively; both n=3) at 60 minutes post-hypoxia. Thus, shorter intervals in an otherwise similar mAIH protocol consisting of 3x1 minute hypoxic episodes significantly enhance pLTF (1-minute: 146 ± 15%, n=5; 2 minute: 92 ± 17%, n = 3). Two, 5-minute hypoxic episodes with a single 15-minute inter-hypoxic interval still elicited pLTF of 51 ± 26% (n=4). These preliminary findings suggest both the hypoxic episode and interval duration are important determinants of mAIH-induced pLTF. Optimizing AIH-induced motor plasticity is necessary as we harness its therapeutic potential to treat severe neuromuscular disorders that compromise breathing. Supported by: NIH HL147554, HL148030, T32HL134621 (ABM) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no ad