反复短暂的缺氧会导致膈神经输出持续增加,持续时间远远超过急性间歇性缺氧(AIH)暴露(即,膈长期促进;pLTF)。用安帕肯预处理,变构调节AMPA受体的药物,使一次短暂的缺氧发作产生pLTF,缺氧后持续90分钟。这里,我们检验了安帕金预处理会增强反复缺氧诱发的pLTF程度的假设。在尿烷麻醉中记录膈神经输出,机械通风,和成年雄性Sprague-Dawley大鼠。最初的实验表明,2分钟后,安帕金CX717(15mg/kgiv)引起膈神经吸气爆发幅度的急性增加,达到基线(BL)的70±48%(P=0.01)。这种增加的爆裂没有持续(60分钟时2±32%BL,P=0.9)。当CX717在单次等二氧化碳缺氧发作前2分钟递送时(5分钟,[公式:见正文]=44±9mmHg),发生膈神经爆发幅度的促进(60分钟时96±62%BL,P<0.001)。然而,当CX717在3之前2分钟给予时,5分钟缺氧发作([公式:见正文]=45±6mmHg)pLTF减弱,未达到统计学意义(24±29%BL,P=0.08)。在没有CX717预处理的情况下,3分钟后观察到pLTF(60分钟时74±33%BL,P<0.001),但没有一次缺氧发作(60分钟时1±8%BL,P=0.9)。我们得出的结论是,当安帕肯预处理后反复缺氧时,pLTF不会增强。相反,安帕金和单一缺氧事件的组合似乎是产生持续增加膈运动输出的理想选择。使用安帕金CX717进行NEW&NOTEWORTHY预处理创造了条件,使急性中度缺氧引起膈运动促进,但是当安帕克定预处理后间歇性缺氧时,没有观察到这种反应。因此,在麻醉和脊髓完整的大鼠中,安帕金和一次缺氧的组合似乎是触发呼吸神经可塑性的理想选择。
Repeated short episodes of hypoxia produce a sustained increase in phrenic nerve output lasting well beyond acute intermittent hypoxia (AIH) exposure (i.e., phrenic long-term facilitation; pLTF). Pretreatment with ampakines, drugs which allosterically modulate AMPA receptors, enables a single brief episode of hypoxia to produce pLTF, lasting up to 90 min after hypoxia. Here, we tested the hypothesis that ampakine pretreatment would enhance the magnitude of pLTF evoked by repeated bouts of hypoxia. Phrenic nerve output was recorded in urethane-anesthetized, mechanically ventilated, and vagotomized adult male Sprague-Dawley rats. Initial experiments demonstrated that ampakine CX717 (15 mg/kg iv) caused an acute increase in phrenic nerve inspiratory burst amplitude reaching 70 ± 48% baseline (BL) after 2 min (P = 0.01). This increased bursting was not sustained (2 ± 32% BL at 60 min, P = 0.9). When CX717 was delivered 2 min before a single episode of isocapnic hypoxia (5 min, [Formula: see text] = 44 ± 9 mmHg), facilitation of phrenic nerve burst amplitude occurred (96 ± 62% BL at 60 min, P < 0.001). However, when CX717 was given 2 min before three, 5-min hypoxic episodes ([Formula: see text] = 45 ± 6 mmHg) pLTF was attenuated and did not reach statistical significance (24 ± 29% BL, P = 0.08). In the absence of CX717 pretreatment, pLTF was observed after three (74 ± 33% BL at 60 min, P < 0.001) but not one episode of hypoxia (1 ± 8% BL at 60 min, P = 0.9). We conclude that pLTF is not enhanced when ampakine pretreatment is followed by repeated bouts of hypoxia. Rather, the combination of ampakine and a single hypoxic episode appears to be ideal for producing sustained increase in phrenic motor output.NEW & NOTEWORTHY Pretreatment with ampakine CX717 created conditions that enabled an acute bout of moderate hypoxia to evoke phrenic motor facilitation, but this response was not observed when ampakine pretreatment was followed by intermittent hypoxia. Thus, in anesthetized and spinal intact rats, the combination of ampakine and one bout of hypoxia appears ideal for triggering respiratory neuroplasticity.