A potential early physiological marker for CNS oxygen toxicity: hyperoxic hyperpnea precedes seizure in unanesthetized rats breathing hyperbaric oxygen
Abstract:Hyperbaric oxygen (HBO(2)) stimulates presumptive central CO2-chemoreceptor neurons, increases minute ventilation (V(min)), decreases heart rate (HR) and, if breathed sufficiently long, produces central nervous system oxygen toxicity (CNS-OT; i.e., seizures). The risk of seizures when breathing HBO(2) is variable between individuals and its onset is difficult to predict. We have tested the hypothesis that a predictable pattern of cardiorespiration precedes an impending seizure when breathing HBO2. To test this… Show more
“…Moreover, there is no physiological hyperoxic ventilatory response that compensates for arterial hyperoxemia. In fact, protracted breathing of an extreme hyperoxic gas mixture at P I O 2 >1 ATA O 2 (i.e., hyperbaric oxygen, HBO 2 ) activates a variety of anomalous cardiorespiratory responses that include transient bradycardia followed by tachycardia, hypertension, paradoxical hyperventilation, and other respiratory abnormalities such as coughing, dyspnea, and spasms of the diaphragm and upper airway that precede onset of tonic-clonic seizures [69,87,152]. Collectively, these non-convulsive signs and symptoms (S/Sx) that terminate in tonic-clonic seizures comprise the malady known as CNS oxygen toxicity (CNS-OT).…”
Section: Atmospheric and Brain Po2: Defining Normoxia And Hypoxia Vermentioning
confidence: 99%
“…Initially, cerebral blood flow (CBF) is decreased by vasoconstriction and delays a significant increase in brain tissue PO 2 [8,71,72,75,76,79]. Likewise, minute ventilation decreases initially due to hyperoxic inactivation of peripheral chemoreceptors [69,152]. With extended exposure to HBO 2 , this cardiopulmonary response is overtaken by increased sympathetic outflow resulting in hyperventilation and hypertension [98,100,152].…”
Hyperbaric oxygen (HBO2) is breathed during hyperbaric oxygen therapy and during certain undersea pursuits in diving and submarine operations. What limits exposure to HBO2 in these situations is the acute onset of central nervous system oxygen toxicity (CNS-OT) following a latent period of safe oxygen breathing. CNS-OT presents as various non-convulsive signs and symptoms, many of which appear to be of brainstem origin involving cranial nerve nuclei and autonomic and cardiorespiratory centers, which ultimately spread to higher cortical centers and terminate as generalized tonic-clonic seizures. The initial safe latent period makes the use of HBO2 practical in hyperbaric and undersea medicine; however, the latent period is highly variable between individuals and within the same individual on different days, making it difficult to predict onset of toxic indications. Consequently, currently accepted guidelines for safe HBO2 exposure are highly conservative. This review examines the disorder of CNS-OT and summarizes current ideas on its underlying pathophysiology, including specific areas of the CNS and fundamental neural and redox signaling mechanisms that are thought to be involved in seizure genesis and propagation. In addition, conditions that accelerate the onset of seizures are discussed, as are current mitigation strategies under investigation for neuroprotection against redox stress while breathing HBO2 that extend the latent period, thus enabling safer and longer exposures for diving and medical therapies.
“…Moreover, there is no physiological hyperoxic ventilatory response that compensates for arterial hyperoxemia. In fact, protracted breathing of an extreme hyperoxic gas mixture at P I O 2 >1 ATA O 2 (i.e., hyperbaric oxygen, HBO 2 ) activates a variety of anomalous cardiorespiratory responses that include transient bradycardia followed by tachycardia, hypertension, paradoxical hyperventilation, and other respiratory abnormalities such as coughing, dyspnea, and spasms of the diaphragm and upper airway that precede onset of tonic-clonic seizures [69,87,152]. Collectively, these non-convulsive signs and symptoms (S/Sx) that terminate in tonic-clonic seizures comprise the malady known as CNS oxygen toxicity (CNS-OT).…”
Section: Atmospheric and Brain Po2: Defining Normoxia And Hypoxia Vermentioning
confidence: 99%
“…Initially, cerebral blood flow (CBF) is decreased by vasoconstriction and delays a significant increase in brain tissue PO 2 [8,71,72,75,76,79]. Likewise, minute ventilation decreases initially due to hyperoxic inactivation of peripheral chemoreceptors [69,152]. With extended exposure to HBO 2 , this cardiopulmonary response is overtaken by increased sympathetic outflow resulting in hyperventilation and hypertension [98,100,152].…”
Hyperbaric oxygen (HBO2) is breathed during hyperbaric oxygen therapy and during certain undersea pursuits in diving and submarine operations. What limits exposure to HBO2 in these situations is the acute onset of central nervous system oxygen toxicity (CNS-OT) following a latent period of safe oxygen breathing. CNS-OT presents as various non-convulsive signs and symptoms, many of which appear to be of brainstem origin involving cranial nerve nuclei and autonomic and cardiorespiratory centers, which ultimately spread to higher cortical centers and terminate as generalized tonic-clonic seizures. The initial safe latent period makes the use of HBO2 practical in hyperbaric and undersea medicine; however, the latent period is highly variable between individuals and within the same individual on different days, making it difficult to predict onset of toxic indications. Consequently, currently accepted guidelines for safe HBO2 exposure are highly conservative. This review examines the disorder of CNS-OT and summarizes current ideas on its underlying pathophysiology, including specific areas of the CNS and fundamental neural and redox signaling mechanisms that are thought to be involved in seizure genesis and propagation. In addition, conditions that accelerate the onset of seizures are discussed, as are current mitigation strategies under investigation for neuroprotection against redox stress while breathing HBO2 that extend the latent period, thus enabling safer and longer exposures for diving and medical therapies.
“…Note: Although it is an accepted practice to secure EMG leads with cyanoacrylate 17,18 , an alternative method is to secure the lead cap in place by tying a silk suture knot around it.…”
Accessory respiratory muscles help maintain ventilation when diaphragm function is impaired. The following protocol describes a method for repeated measurements over weeks or months of accessory respiratory muscle activity while simultaneously measuring ventilation in a non-anesthetized freely behaving mouse. The technique includes surgical implantation of a radio transmitter and insertion of electrode leads into the scalene and trapezius muscles to measure electromyogram activity of these inspiratory muscles. Ventilation is measured by whole body plethysmography and animal movement is assessed by video and synchronized with electomyogram activity. Measurements of muscle activity and ventilation in a mouse model of amyotrophic lateral sclerosis are presented to show how this tool can be used to investigate how respiratory muscle activity changes over time and to assess the impact of muscle activity on ventilation. The described methods can easily be adapted to measure activity of other muscles or to assess accessory respiratory muscle activity in additional mouse models of disease or injury.
“…In some experimental models of global cerebral ischemia, hyperoxemia has been shown to be detrimental to the brain, probably also because of its vasoconstrictor effects [ 21 , 22 ]. Hyperoxemia may also provoke or exacerbate seizures, which could aggravate brain injury [ 23 , 24 ]. Figure 1 Summary of cellular and systemic effects of high oxygen (O 2 ) concentrations.…”
Section: Post-cardiac Arrest Syndrome: the Role Of Oxygenmentioning
Although experimental studies have suggested that a high arterial oxygen pressure (PaO2) might aggravate post-anoxic brain injury, clinical studies in patients resuscitated from cardiac arrest (CA) have given conflicting results. Some studies found that a PaO2 of more than 300 mm Hg (hyperoxemia) was an independent predictor of poor outcome, but others reported no association between blood oxygenation and neurological recovery in this setting. In this article, we review the potential mechanisms of oxygen toxicity after CA, animal data available in this field, and key human studies dealing with the impact of oxygen management in CA patients, highlighting some potential confounders and limitations and indicating future areas of research in this field. From the currently available literature, high oxygen concentrations during cardiopulmonary resuscitation seem preferable, whereas hyperoxemia should be avoided in the post-CA care. A specific threshold for oxygen toxicity has not yet been identified. The mechanisms of oxygen toxicity after CA, such as seizure development, reactive oxygen species production, and the development of organ dysfunction, need to be further evaluated in prospective studies.
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