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Long-term facilitation of the phrenic nerve activity in rats following intermittent hypoxia

There is abundant information of neuromodulary effects of serotonin and GABA that have been released and accumulated within respiratory regions under physiological and pathological conditions. The functional significance of ongoing neuromodulation is seen in continuous adjustments of neuronal excitability such as respiratory plasticity known as long term facilitation, LTF. Repeated exposure to acute intermittent hypoxia serves as a suitable model for investigation of long term respiratory plasticity. Urethane anesthesia is a popular choice in animal studies of respiratory plasticity, although the role of other anesthetics such as propofol and remifentanil on manifestation of LTF has been highlighted in recent studies. LTF might be a beneficial factor for maintaining upper airway muscles activity, thus stabilizing upper airway patency in OSA patients with repeated exposures to apopnea/hypopnea during sleep. Aim was to investigate the effects of urethane and propofol anesthesia on induction of pLTF, as well as to test the possible role of opioid and serotonin 5-HT1A receptors in induction and preservation of pLTF.

 Adult, male, anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague– Dawley rats were exposed to an acute intermittent hypoxia (AIH) protocol. There were three experimental and three control groups: I anesthetized with propofol infusion ; II anesthetized with remifentanil infusion and urethane ; III urethane anesthetized and WAY treated. Peak phrenic nerve activity, burst frequency, and respiratory rhythm parameters were analyzed during hypoxia, as well as at 15, 30, and 60 min after the end of the last hypoxic episode. In urethane anesthetized rats there was a significant increase of the peak phrenic nerve activity following AIH at 60 min indicating pLTF. Propofol, as well as remifentanil and WAY-100635 prevented induction of the pLTF. Additionally, administration of WAY-100635 after pLTF developed impaired preservation of pLTF.

 pLTF was induced in urethane anesthetized rats following the specific acute intermittent hypoxia protocol, but not during the propofol anesthesia. Also, there was an important role for opioid and serotonin 5-HT1A receptors in pLTF. The results suggest very sensitive mechanism of respiratory neuroplasticity following the acute intermittent hypoxia stimulus.

long-term facilitation; respiratory plasticity; serotonin; anesthesia; remifentanil; propofo

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