Prenatal Nicotine Exposure Alters Central Cardiorespiratory Responses to Hypoxia in Rats: Implications for Sudden Infant Death Syndrome

Abstract

Maternal cigarette smoking and prenatal nicotine exposure are the highest risk factors for sudden infant death syndrome (SIDS). During hypoxia, respiratory frequency and heart rate transiently increase and subsequently decrease. These biphasic cardiorespiratory responses normally serve to prolong survival during hypoxia by reducing the metabolic demands of cardiac and respiratory muscles. However, exaggerated responses to hypoxia may be life threatening and have been implicated in SIDS. Heart rate is primarily determined by the activity of brainstem preganglionic cardioinhibitory vagal neurons (CVNs) in the nucleus ambiguus. We developed an in vitro rat brainstem slice preparation that maintains rhythmic inspiratory-related activity and contains fluorescently labeled CVNs. Synaptic inputs to CVNs were examined using patch-clamp electrophysiological techniques. Hypoxia evoked a biphasic change in the frequency of both GABAergic and glycinergic IPSCs in CVNs, comprised of an initial increase followed by a decrease in IPSC frequency. Prenatal exposure to nicotine changed the GABAergic response to hypoxia from a biphasic response to a precipitous decrease in spontaneous GABAergic IPSC frequency. This study establishes a likely neurochemical mechanism for the heart rate response to hypoxia and a link between prenatal nicotine exposure and an exaggerated bradycardia during hypoxia that may contribute to SIDS.

Purinergic P2X receptors facilitate inhibitory GABAergic and glycinergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

“…Heart rate responses to hypoxia include a biphasic increase followed by a decrease in heart rate. Previous work has shown hypoxia evokes a biphasic augmentation followed by a reduction in GABAergic and glycinergic activity to CVNs, and this is likely is responsible for the initial tachycardia followed by a bradycardia in response to hypoxia (Neff et al, 2004). It is likely that the purinergic facilitation of GABAergic and glycinergic activity to CVNs examined in this study mediates the initial increase in inhibitory inputs to CVNs during hypoxia.…”

Ani Bebek Ölümü Sendromu

“…Baz› ABÖS olgular›n›n ailelerinde mast hücre sal›n›m› fazlal›¤› ve degranülasyonu göste-rilmifl, baz› olgularda da degranülasyon bulunmufltur. Bu bulgular, anaflaktoid reaksiyon riskinin de artt›¤›n› düflündürmektedir (56)(57)(58). Emery ve ark.…”

“…Beyin sap›n›n, ABÖS içindeki rolünü çözümlemek için arkuat nükleus belirli bir dikkat toplam›flt›r. Kan›tlar, bebe¤in kolay zarar görebilir olmas›n›n bu yap›dan kaynakland›¤›n› gös-termektedir, arkuat nükleusta geliflimsel defektler göste-rilmifltir (52,53,57). Solunum anormallikleri; uzam›fl apne, s›k-k›sa süreli apne ve periyodik solunumu kapsar.…”

“…Üst solunum yolu t›kanmas› ve/veya yüzüko-yun uyku pozisyonundan do¤an asfiktik bir durumda normal bir bebe¤in sinir sistemi, ilerleyen hiperkapni ile hipoksiyi saptar ve bir seri koruyucu refleks ve uyar›m ile cevap verir. Arkuat nükleustaki geliflimsel defekten dolay›, ABÖS olgusu uyar›lamaz, a¤lamaz, ventilasyonu artt›ramaz, hiperkapni ile hipoksiye cevap olarak bafl›n› oynatamaz ve ölüm gerçekleflebilir (18,51,57). Uyan›kl›k yan›t›n›n eksikli¤i ABÖS aç›s›ndan risk tafl›makla birlikte di¤er biyolojik ve çevresel risk etkenlerinin yoklu¤un-da yeterli de¤ildir.…”

“…Hipotezlerde öne sürülen kalp ileti bozukluklar› ve UQTS'nun saptanmas› için yap›lan elektrokardiyografi taramalar›, ABÖS s›kl›¤›n›n düflük olmas›, etkin bir tedavi stratejisinin olmamas›, testin özgünlük ve duyarl›l›¤›-n›n düflük olmas› nedeniyle etkin bulunmam›flt›r (57,60).…”