The impact of intermittent or sustained carbon dioxide on intermittent hypoxia initiated respiratory plasticity. What is the effect of these combined stimuli on apnea severity?

Mateika, Jason H.; Panza, Gino S.; Alex, Raichel M.; El‐Chami, Mohamad

doi:10.1016/j.resp.2017.10.008

Cited by 22 publications

(18 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been proposed that episodic stimulation of the central chemoreceptors occurring during apneas leads to exaggerated sympathetic responses (40) and that breathing disorders in patients with HF are a function of chemoreceptor-mediated hyperventilation and subsequent decreases in PCO 2 below the apneic threshold (22). Previous work shows that periodic stimulation of CC triggers ventilatory plasticity, characterized by changes in poststimulation normoxic minute ventilation (V E) (4,27). However, the relationship between this phenomenon and disordered breathing patterns is controversial (27), and the effects of episodic stimulation of CC on breathing disorders in HF has not been studied yet.…”

Section: Introductionmentioning

confidence: 99%

Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure

Andrade

Toledo

Pereyra

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Enhanced central chemoreflex (CC) gain is observed in volume overload heart failure (HF) and is correlated with autonomic dysfunction and breathing disorders. The aim of this study was to determine the role of the CC in the development of respiratory and autonomic dysfunction in HF. Volume overload was surgically created to induce HF in male Sprague-Dawley rats. Radiotelemetry transmitters were implanted for continuous monitoring of blood pressure and heart rate. After recovering from surgery, conscious unrestrained rats were exposed to episodic hypercapnic stimulation [EHS; 10 cycles/5 min, inspiratory fraction of carbon dioxide ([Formula: see text]) 7%] in a whole body plethysmograph for recording of cardiorespiratory function. To determine the contribution of CC to cardiorespiratory variables, selective ablation of chemoreceptor neurons within the retrotrapezoid nucleus (RTN) was performed via injection of saporin toxin conjugated to substance P (SSP-SAP). Vehicle-treated rats (HF+Veh and Sham+Veh) were used as controls for SSP-SAP experiments. Sixty minutes post-EHS, minute ventilation was depressed in sham animals relative to HF animals (ΔV̇e: −5.55 ± 2.10 vs. 1.24 ± 1.35 mL/min 100 g, P < 0.05; Sham+Veh vs. HF+Veh). Furthermore, EHS resulted in autonomic imbalance, cardiorespiratory entrainment, and ventilatory disturbances in HF+Veh but not Sham+Veh rats, and these effects were significantly attenuated by SSP-SAP treatment. Also, the apnea-hypopnea index (AHI) was significantly lower in HF+SSP-SAP rats compared with HF+Veh rats (AHI: 5.5 ± 0.8 vs. 14.4 ± 1.3 events/h, HF+SSP-SAP vs. HF+Veh, respectively, P < 0.05). Finally, EHS-induced respiratory-cardiovascular coupling in HF rats depends on RTN chemoreceptor neurons because it was reduced by SSP-SAP treatment. Overall, EHS triggers ventilatory plasticity and elicits cardiorespiratory abnormalities in HF that are largely dependent on RTN chemoreceptor neurons.

show abstract

Section: Introductionmentioning

confidence: 99%

Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure

Andrade

Toledo

Pereyra

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…While there are likely many possible explanations for a lack of compensatory plasticity in individuals with sleep apnoea (Mateika & Komnenov, ; Mateika et al . ), our findings suggest that in some individuals, concurrent induction of iMF and LTF may occlude compensatory respiratory behaviours via cross‐talk inhibition of their distinct signalling pathways. Consistent with this hypothesis, evidence suggests that

P_{aC O_{2}}

has to be increased by a small amount (3–4 mmHg) during intermittent hypoxic exposures in order to reliably elicit LTF in humans (Harris et al .…”

Section: Discussionmentioning

confidence: 57%

“…; Mahamed & Mitchell, ; Mateika et al . ); thus, we conclude that antagonistic signalling convergence from co‐induction of iMF and LTF by reduced respiratory neural activity and hypoxia, respectively, obstructs plasticity during hypoxic neural apnoeas, potentially explaining the absence of adaptive breathing behaviours in some individuals with sleep apnoea.…”

Section: Discussionmentioning

confidence: 79%

“…), presumably to prevent arterial CO 2 from falling below the apnoeic threshold (and hence, reducing respiratory neural activity; Mateika et al . ). In our studies, we chose to use a ‘ventilator apnoea’ (i.e.…”

Section: Discussionmentioning

confidence: 97%

“…The reasons for this are not well understood; however, it is possible that mild hypercapnia prevents hypoxia‐induced hyperventilation from lowering

P_{aC O_{2}}

below/near the apnoeic threshold, thereby creating a central apnoea/hypopnoea (Mateika et al . ) and thus occluding plasticity by the concurrent exposure to both LTF and iMF‐inducing stimuli.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Competing mechanisms of plasticity impair compensatory responses to repetitive apnoea

Fields

Braegelmann

Meza

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

Key pointsr Intermittent reductions in respiratory neural activity, a characteristic of many ventilatory disorders, leads to inadequate ventilation and arterial hypoxia. Both intermittent reductions in respiratory neural activity and intermittent hypoxia trigger compensatory enhancements in inspiratory output when experienced separately, forms of plasticity called inactivity-induced inspiratory motor facilitation (iMF) and long-term facilitation (LTF), respectively.r Reductions in respiratory neural activity that lead to moderate, but not mild, arterial hypoxia occludes plasticity expression, indicating that concurrent induction of iMF and LTF impairs plasticity through cross-talk inhibition of their respective signalling pathways.r Moderate hypoxia undermines iMF by enhancing NR2B-containing NMDA receptor signalling, which can be rescued by exogenous retinoic acid, a molecule necessary for iMF.r These data suggest that in ventilatory disorders characterized by reduced inspiratory motor output, such as sleep apnoea, endogenous mechanisms of compensatory plasticity may be impaired, and that exogenously activating respiratory plasticity may be a novel strategy to improve breathing.Abstract Many forms of sleep apnoea are characterized by recurrent reductions in respiratory neural activity, which leads to inadequate ventilation and arterial hypoxia. Both recurrent reductions in respiratory neural activity and hypoxia activate mechanisms of compensatory plasticity that augment inspiratory output and lower the threshold for apnoea, inactivity-induced inspiratory motor facilitation (iMF) and long-term facilitation (LTF), respectively. However, despite frequent concurrence of reduced respiratory neural activity and hypoxia, mechanisms that induce and regulate iMF and LTF have only been studied separately. Here, we demonstrate that recurrent reductions in respiratory neural activity ('neural apnoea') accompanied by cessations in ventilation that result in moderate (but not mild) hypoxaemia do not elicit increased inspiratory output, suggesting that concurrent induction of iMF and LTF occludes plasticity. A key role for NMDA receptor activation in impairing plasticity following concurrent neural apnoea and hypoxia is indicated since recurrent hypoxic neural apnoeas triggered increased phrenic inspiratory Daryl Fields is currently a neurosurgery resident at the University of Pittsburgh. He completed his medical degree and research doctorate at the University of Wisconsin Madison under the mentorship of Dr Tracy Baker, PhD. Daryl's research is focused on creating readily translatable therapies for movement control disorders: (1) development of animal models to better understand deficits in movement control and (2) development of pharmacological therapies for improved motor rehabilitation. He has contributed to the development of several novel research directions that continue to progress the field of motor control/rehabilitation. 3952 D. P. Fields and others J Physiol 597.15 output in rats in which spinal NR2B-containing ...

show abstract

Functional role of carbon dioxide on intermittent hypoxia induced respiratory response following mid-cervical contusion in the rat

Lin

Vinit

Lee

2021

Experimental Neurology

View full text Add to dashboard Cite

The impact of intermittent or sustained carbon dioxide on intermittent hypoxia initiated respiratory plasticity. What is the effect of these combined stimuli on apnea severity?

Cited by 22 publications

References 92 publications

Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure

Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure

Competing mechanisms of plasticity impair compensatory responses to repetitive apnoea

Functional role of carbon dioxide on intermittent hypoxia induced respiratory response following mid-cervical contusion in the rat

Contact Info

Product

Resources

About