Hypoxia-induced hypotension elicits adenosine-dependent phrenic long-term facilitation after carotid denervation

Exp Neurol, 2020 · DOI: 10.1016/j.expneurol.2020.113429 · Published: November 1, 2020

Simple Explanation

This study investigates how the body adapts to low oxygen levels (hypoxia) and its impact on breathing, particularly focusing on a phenomenon called phrenic long-term facilitation (pLTF), which is a persistent increase in the activity of the phrenic nerve that controls breathing. The researchers explored how pLTF occurs in rats that have had their carotid bodies (oxygen sensors) removed (CBX). They found that after CBX, low oxygen conditions lead to exaggerated drops in blood pressure (hypotension), which reduces oxygen supply to the spinal cord. This spinal cord hypoxia triggers the release of a chemical called adenosine, which then activates specific receptors (A2A) in the spinal cord, resulting in pLTF. Preventing the drop in blood pressure normalized spinal tissue oxygen and abolished residual pLTF.

Study Duration

Not specified

Participants

50 adult (300–500 gram) male Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
Carotid denervation leads to more severe hypoxia-induced hypotension compared to sham rats.
2
Preventing hypotension mitigates spinal tissue hypoxia during moderate AIH and abolishes residual pLTF.
3
Spinal A2A receptor inhibition blunted/abolished residual pLTF in CBX rats.

Research Summary

The study aimed to understand mechanisms giving rise to residual pLTF following moderate AIH in rats with carotid denervation, hypothesizing that carotid denervation enables greater hypotension during AIH, impairing spinal oxygen delivery and eliciting pLTF via an A2A receptor-dependent mechanism. Experiments involved measuring spinal PtO2 and phrenic nerve activity in anesthetized, paralyzed, vagotomized, and ventilated rats during a moderate AIH protocol. The key finding was that exaggerated hypotension within hypoxic episodes following carotid denervation elicits residual moderate AIH-induced pLTF by an adenosine-dependent mechanism.

Practical Implications

Clinical Relevance for Spinal Cord Injury

Patients with systemic hypotension, common after spinal cord injury, may have compromised spinal tissue oxygenation during therapeutic AIH, suggesting milder hypoxic episodes may be more appropriate.

Optimizing AIH Protocols

Case-specific adjustments in AIH protocols should be considered for individuals with impaired blood pressure regulation or compromised oxygen delivery to minimize spinal tissue hypoxia.

Therapeutic Benefits of Mild AIH

Milder AIH protocols may optimize the serotonin-dependent therapeutic benefits of repetitive AIH by minimizing spinal tissue hypoxia and adenosinergic constraints.

Study Limitations

1
Mechanisms of reduced spinal PtO2 during moderate AIH in CBX rats were not directly investigated in this study.
2
Whether or not spinal adenosine accumulation is sufficient to cause a long-lasting increase in spinal PtO2 observed following the AIH protocol requires further investigation.
3
Sample sizes were small for antagonist experiments (n=2-4).

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