Phrenic Long-term Facilitation Following Severe Acute Intermittent Hypoxia Is Preserved in Geriatric Male Rats

Abstract

Acute intermittent hypoxia (AIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Both moderate and severe AIH elicit phenotypically similar pLTF but do so via completely distinct cellular mechanisms. With moderate AIH (mAIH), pLTF arises from a serotonin-dominant, adenosine-constrained mechanism. In aged rats, mAIH-induced pLTF is impaired due to increased basal spinal adenosine levels, which constrain serotonin-dependent pLTF. With severe AIH (sAIH), pLTF arises from an adenosine-dominant, serotonin-constrained mechanism. Since spinal adenosine levels are elevated in aged male rats, we hypothesized that age would actually enhance sAIH-induced- pLTF. Young (~3.5 month) and aged (~20 month) male Sprague Dawley rats were urethane anesthetized, artificially ventilated, vagotomized, paralyzed, and exposed to sAIH (3, 5-minute episodes; arterial Po2 = 25-30 mmHg). Integrated phrenic nerve burst activity was measured before (baseline), during hypoxic episodes and 60 minutes after sAIH. Neither baseline phrenic burst amplitude, the short-term hypoxic phrenic response nor pLTF magnitude (assessed as % change in phrenic burst amplitude from baseline to 60 minutes post-sAIH) were different in aged versus young rats (120 ± 22% vs. 98 ± 17%, respectively). Thus, aged male rats preserve the capacity for adenosine driven phrenic motor plasticity. Although we cannot conclude that sAIH-induced pLTF is actually increased, age effects on adenosine versus serotonin-driven plasticity are clearly different. NIH HL148030. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.