A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

Goldwater, Paul N.

doi:10.1186/1741-7015-9-64

Cited by 36 publications

(26 citation statements)

References 130 publications

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“…In our current study, dead pups were rapidly eaten by the dam, so the quality of tissue available for autopsy was poor. It will be important to analyse the cause of death by ECG telemetry and immediate autopsy, to compare with human pathological findings in SIDS (Goldwater, 2011). …”

Section: Discussionmentioning

confidence: 99%

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A mouse model to study the link between hypoxia, long QT interval and sudden infant death syndrome

Neary¹,

Mohun²,

Breckenridge³

2012

Disease Models &Amp; Mechanisms

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SUMMARYThe pathology of sudden infant death syndrome (SIDS) is poorly understood. Many risk factors, including hypoxia, have been identified. Prolongation of the ECG QTc interval is associated with elevated risk of SIDS but its aetiology in most cases remains unknown. We have characterised ECG changes in the newborn mouse in the hours and days following birth. There was a steady increase in heart rate alongside significant decreases in QTc interval, QRS duration and QTc dispersion over the first 10 postnatal days. Birth into hypoxia (10% FiO2) prevented electrocardiac maturation, downregulated cardiac ion-channel expression and led to neonatal death. We found that risk of death decreased with increasing age of exposure to hypoxia. Genetic elevation of cardiac hypoxia-signalling after birth in αMHC-Cre::VHLfl/fl mice also prevented electrocardiographic maturation, leading to arrhythmia and death before weaning. Immunohistochemistry and western blotting revealed internalisation and dephosphorylation of Connexin43. We conclude that increased ambient oxygen concentration after birth drives maturation of the cardiac electrical conduction system, failure of which leads to aberrant ion channel and Connexin43 expression and predisposes to arrhythmia and sudden death. This is consistent with known risk factors of SIDS and provides a link between neonatal hypoxia, ECG abnormalities and sudden death.

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Section: Discussionmentioning

confidence: 99%

“…Since the ‘back to sleep’ campaign in 1994, there have been no further reductions in SIDS incidence. A number of causative mechanisms have been proposed to lead to SIDS, but without any unifying theory or correlation with pathological findings (Goldwater, 2011). …”

Section: Introductionmentioning

confidence: 99%

A mouse model to study the link between hypoxia, long QT interval and sudden infant death syndrome

Neary¹,

Mohun²,

Breckenridge³

2012

Disease Models &Amp; Mechanisms

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“…A wide range of factors from maternal behaviors such cigarette smoking and substance abuse (Iyasu et al, 2002; Blair et al, 2006; Horne, 2006; Moon et al, 2007; Moon, 2011) to sleeping conditions such as soft bedding and sleeping in the prone position (Willinger et al, 1994; Mitchell et al, 1999b; Mitchell et al, 1999a) have been identified with an increased risk for SIDS. Although, we have gained many new insights into the mechanistic basis of this syndrome, there are still many open questions (Morris, 1999; Kinney et al, 2009; Goldwater, 2011; Tfelt-Hansen et al, 2011). This complexity in the etiology of SIDS is readily exemplified by the shifts in SIDS demographic data.…”

Section: Cardiorespiratory Dysautonomiamentioning

confidence: 99%

Cardiorespiratory coupling in health and disease

Garcia¹,

Koschnitzky²,

Dashevskiy³

et al. 2013

Autonomic Neuroscience

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Cardiac and respiratory activities are intricately linked both functionally as well as anatomically through highly overlapping brainstem networks controlling these autonomic physiologies that are essential for survival. Cardiorespiratory coupling (CRC) has many potential benefits creating synergies that promote healthy physiology. However, when such coupling deteriorates autonomic dysautonomia may ensue. Unfortunately there is still an incomplete mechanistic understanding of both normal and pathophysiological interactions that respectively give rise to CRC and cardiorespiratory dysautonomia. Moreover, there is also a need for better quantitative methods to assess CRC. This review addresses the current understanding of CRC by discussing: (1) the neurobiological basis of respiratory sinus arrhythmia (RSA); (2) various disease states involving cardiorespiratory dysautonomia; and (3) methodologies measuring heart rate variability and RSA.

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“…It is defined as the unexpected sudden death of a child less than 1 year of age in which an autopsy does not show an explainable cause of death (Hauck and Tanabe, 2008). Although the underlying mechanism has remained elusive; several theories propose failure of respiratory and/or cardiac pathways (Guntheroth, 1995; Horne et al, 2005; Goldwater, 2011; Garcia et al, 2013). Petechiae on autopsy of SIDS cases as well as histological evidence of mild respiratory infection in a high percentage of SIDS victims favor a respiratory-related related mechanism (Guntheroth, 1995; Trachtenberg et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Inner ear insult ablates the arousal response to hypoxia and hypercarbia

Allen

Garcia²,

Tang³

et al. 2013

Neuroscience

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Introduction Sudden Infant Death Syndrome (SIDS) remains the leading cause of infant mortality in Western societies. A prior study identified an association between hearing suppression on the newborn hearing test and subsequent death from SIDS. This is the first finding of an abnormality in SIDS cases prior to death. A following study identified that inner ear dysfunction precipitates a marked suppression of the hypercapnic ventilatory response (HCVR). Failure of arousal has been proposed to be a key component in SIDS. The objective of the present study was to assess whether inner ear dysfunction not only weakens the hypercapnic response, but also plays a role in suppressing the arousal response to suffocating gas mixtures. Methods Wild-type mice (n = 28) received intra-tympanic gentamicin (IT-Gent) injections bilaterally or unilaterally to precipitate inner ear hair cell dysfunction. Three control groups (n = 22) received intra-tympanic saline (IT-Saline) bilaterally or unilaterally (right or left), or intra-peritoneal gentamicin (IP-Gent). The body movement arousal responses to severe hypoxia–hypercarbia combined (5% CO2 in nitrogen) were tested under light anesthesia 8 days following the administration of gentamicin or saline. Results After injections, the bilateral and unilateral IT-Gent-treated animals behaved similarly to controls, however the HCVR as well as the arousal movements in response to severe hypoxia–hypercarbia were suppressed in IT-Gent-treated animals compared to control animals (P < 0.05). Thus the HCVR was significantly decreased in the bilateral (n = 9) and unilateral IT-Gent-treated mice (n = 19) compared to bilateral (n = 7) and unilateral IT-Saline (n = 9) control groups (p < 0.05). Arousal movements were suppressed in the bilateral IT-Gent group (n = 9) compared to bilateral IT-Saline controls (n = 7, P < 0.0001) and in the unilateral IT-Gent group (n = 19) compared to unilateral IT-Saline controls (n = 10, P < 0.0001). Discussion The findings support the theory that inner ear dysfunction could be relevant in the pathophysiology of SIDS. The inner ear appears to play a key role in arousal from suffocating gas mixtures that has not been previously identified.

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A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

Cited by 36 publications

References 130 publications

A mouse model to study the link between hypoxia, long QT interval and sudden infant death syndrome

A mouse model to study the link between hypoxia, long QT interval and sudden infant death syndrome

Cardiorespiratory coupling in health and disease

Inner ear insult ablates the arousal response to hypoxia and hypercarbia

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