Montandon Gaspard, Bairam Aida, Kinkead Richard
Départment de Pédiatrie, Université Laval, Centre de recherche Hôpital St-François d' Assise, Québec, Canada.
Pediatr Res. 2006 Apr;59(4 Pt 1):519-24. doi: 10.1203/01.pdr.0000203105.63246.8a.
Caffeine is an adenosine receptor antagonist commonly used as a respiratory stimulant to treat neonatal apneas of premature newborn. Neonatal caffeine treatment (NCT) has long-term effects on adenosine receptor expression and distribution; however, the potential effects of NCT on respiratory control development are unknown. To address this issue, rat pups received orally each day from postnatal d 3-12, 15 mg/kg of caffeine (NCT), water (vehicle), or were undisturbed during early life (control). Measurements of resting ventilation, apnea index, and ventilatory response to moderate hypercapnia (FiCO2 = 0.05) were made using whole-body plethysmography at postnatal d 20 (juvenile) and adulthood. At d 20, resting respiratory variables were not affected by the treatments. Juvenile NCT male rats showed a 22% higher minute ventilation response to hypercapnia than vehicle rats. However, oral gavage alone increased the frequency component of the response by 11%. In adult males, caffeine increased the resting respiratory frequency by 15%. In these animals, the tidal volume response to hypercapnia was increased by 15%, whereas the frequency response was decreased by 20%. In juvenile and adult females, no differences were observed between treatments. In juvenile rats of both sexes, gavage increased the apnea index by at least 200%. These results show that NCT and gavage influence respiratory control during early life and that these effects persist until adulthood. The underlying mechanisms are unclear, but may be related to persistent changes in adenosinergic neurotransmission because neonatal caffeine administration increases A1 adenosine receptor density in adult rats.
咖啡因是一种腺苷受体拮抗剂，常用作呼吸兴奋剂来治疗早产新生儿的呼吸暂停。新生儿咖啡因治疗（NCT）对腺苷受体的表达和分布具有长期影响；然而，NCT对呼吸控制发育的潜在影响尚不清楚。为了解决这个问题，从出生后第3天至12天，给幼鼠每日口服15mg/kg咖啡因（NCT）、水（载体对照），或者在幼年期不进行处理（对照）。在出生后第20天（幼年）和成年期，使用全身体积描记法测量静息通气、呼吸暂停指数以及对中度高碳酸血症（FiCO2 = 0.05）的通气反应。在第20天，静息呼吸变量不受处理的影响。幼年NCT雄性大鼠对高碳酸血症的分钟通气反应比载体对照大鼠高22%。然而，单独经口灌胃使反应的频率成分增加了11%。在成年雄性大鼠中，咖啡因使静息呼吸频率增加了15%。在这些动物中，对高碳酸血症的潮气量反应增加了15%，而频率反应降低了20%。在幼年和成年雌性大鼠中，各处理组之间未观察到差异。在两性幼年大鼠中，灌胃使呼吸暂停指数至少增加了200%。这些结果表明，NCT和灌胃在幼年期影响呼吸控制，且这些影响持续至成年期。其潜在机制尚不清楚，但可能与腺苷能神经传递的持续变化有关，因为新生期给予咖啡因会增加成年大鼠A1腺苷受体的密度。
