Continuous infusion of prostaglandin E1 (PGE1) is used to maintain ductus arteriosus patency in infants with critical congenital heart disease, but it can also cause central apnea suggesting an effect on respiratory neural control. In this study, we investigated whether 1) PGE1 inhibits the various phases of the acute hypoxic ventilatory response (HVR; an index of respiratory control dysfunction) and increases apnea incidence in neonatal rats; and 2) whether these changes would be reversible with caffeine pretreatment. Whole body plethysmography was used to assess the HVR and apnea incidence in neonatal rats 2 h following a single bolus intraperitoneal injection of PGE1 with and without prior caffeine treatment. Untreated rats exhibited a biphasic HVR characterized by an initial increase in minute ventilation followed by a ventilatory decline of the late phase (~5th minute) of the HVR. PGE1 had a dose-dependent effect on the HVR. Contrary to our hypothesis, the lowest dose (1 µg/kg) of PGE1 prevented the ventilatory decline of the late phase of the HVR. However, PGE1 tended to increase postsigh apnea incidence and the coefficient of variability (CV) of breathing frequency, suggesting increased respiratory instability. PGE1 also decreased brainstem microglia mRNA and increased neuronal nitric oxide synthase (nNOS) and platelet-derived growth factor-β (PDGF-β) gene expression. Caffeine pretreatment prevented these effects of PGE1, and the adenosine A2A receptor inhibitor MSX-3 had similar preventative effects. Prostaglandin appears to have deleterious effects on brainstem respiratory control regions, possibly involving a microglial-dependent mechanism. The compensatory effects of caffeine or MSX-3 treatment raises the question of whether prostaglandin may also operate on an adenosine-dependent pathway.

中文翻译：

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咖啡因可防止新生大鼠中前列腺素 E1 诱导的呼吸控制障碍：对患有严重先天性心脏病的婴儿的影响。

连续输注前列腺素 E1 (PGE1) 用于维持患有严重先天性心脏病的婴儿的动脉导管通畅，但它也可能导致中枢性呼吸暂停，表明对呼吸神经控制有影响。在这项研究中，我们研究了 1) PGE1 是否抑制了急性缺氧通气反应 (HVR；呼吸控制功能障碍的指标) 的各个阶段并增加了新生大鼠的呼吸暂停发生率；2）这些变化是否可以通过咖啡因预处理逆转。使用全身体积描记术评估新生大鼠单次腹膜内注射 PGE1 后 2 小时的 HVR 和呼吸暂停发生率，有或没有咖啡因治疗。未治疗的大鼠表现出双相 HVR，其特征是每分钟通气量的初始增加，然后是 HVR 后期（~第 5 分钟）的通气量下降。PGE1 对 HVR 具有剂量依赖性影响。与我们的假设相反，PGE1 的最低剂量 (1 µg/kg) 阻止了 HVR 后期的通气下降。然而，PGE1 倾向于增加呼吸后呼吸暂停的发生率和呼吸频率的变异系数 (CV)，表明呼吸不稳定性增加。PGE1 还降低脑干小胶质细胞 mRNA 并增加神经元一氧化氮合酶 (nNOS) 和血小板衍生生长因子-β (PDGF-β) 基因表达。咖啡因预处理阻止了 PGE1 的这些作用，腺苷 A2A 受体抑制剂 MSX-3 具有类似的预防作用。前列腺素似乎对脑干呼吸控制区有有害影响，可能涉及小胶质细胞依赖性机制。咖啡因或 MSX-3 治疗的代偿作用提出了前列腺素是否也可能在腺苷依赖性途径上起作用的问题。