Hypoventilation in ponies after carotid body denervation

Obstructive sleep apnea is a frequent medical condition consisting in repetitive sleep-related episodes of upper airways obstruction and concurrent events of arterial blood hypoxia. To this condition there is a frequent association of cardiovascular and other pathologies conforming the obstructive sleep apnea syndrome (OSAS). Laboratory models of OSAS consist in animals exposed repetitive episodes of Intermittent hypoxia (IH) which also develop cardiovascular pathology, mostly hypertension. The overall OSAS pathophysiology appears to be linked to the repetitive hypoxia, being proposed that it causes a sensitization of carotid body (CB) chemoreflex leading to a hyperreactivity of the sympathetic nervous system. However, this proposal is uncertain because normo or hypoventilation and normal plasma catecholamines are not infrequent findings in patients with OSAS and IH animals. Aiming to solve these issues we have studied in a rat model of IH the entire CB chemoreflex arch including activity of chemoreceptor cells and CB generated afferent activity to brainstem; efferent activity was measured as ventilation in normoxia, hypoxia and hypercapnia. Norepinephrine turnover in renal artery sympathetic endings was also assessed. Findings indicate a sensitization of the CB function to hypoxia evidenced by exaggerated chemoreceptor cell and CB afferent activity. At the same time IH rats exhibited marked hypoventilation in all studied conditions and increased turnover of norepinephrine in sympathetic endings. We conclude that IH causes a bias in the integration of the input arising from the CB with a diminished drive of ventilation and an exaggerated activation of brainstem sympathetic neurons. 2

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“…In the present work we have studied the effects of 8 and 15 days duration IH of moderate intensity as defined by nadir arterial PO 2 …”

Section: Discussionmentioning

confidence: 99%

“…Each obstruction produces a fall in arterial PO 2 Exposure to intermittent hypoxia. Four rats were housed in hermetically shielding transparent methacrylate chambers (16 l), along with food and water.…”

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confidence: 99%

Carotid body function and ventilatory responses in intermittent hypoxia. evidence for anomalous brainstem integration of arterial chemoreceptor input

González‐Martín

Vega-Agapito

Conde

et al. 2011

Journal Cellular Physiology

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“…In cats (88) and rats (11,60,82), there is considerable recovery in the chemoreflex a few weeks after CBD and near total recovery a year later. In dogs (80), ponies (8,9), and goats (31,75), there is no significant or only a small recovery a few weeks after CBD, and in ponies there is less than 25% recovery 4 yr after CBD (Fig. 1).…”

Section: Denervation Of Peripheral Chemoreceptorsmentioning

confidence: 99%

“…After CBD, breathing and/or hypoventilation is shown to be initially reduced during room air breathing at rest (8,9,25,26,57,75,80,83) (Fig. 1) and during exercise (74,75,77), but there is plasticity or recovery from the hypoventilation (Fig.…”

Section: Denervation Of Peripheral Chemoreceptorsmentioning

confidence: 99%

Invited Review: Plasticity in the control of breathing following sensory denervation

Forster

2003

Journal of Applied Physiology

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Forster, H. V. Invited Review: Plasticity in the control of breathing following sensory denervation. J Appl Physiol 94: 784-794, 2003; 10.1152/japplphysiol.00602.2002.-The purpose of this manuscript is to review the results of studies on the recovery or plasticity following a denervation-or lesion-induced change in breathing. Carotid body denervation (CBD), lung denervation (LD), cervical (CDR) and thoracic (TDR) dorsal rhizotomy, dorsal spinal column lesions, and lesions at pontine, medullary, and spinal sites all chronically alter breathing. The plasticity after these is highly variable, ranging from near complete recovery of the peripheral chemoreflex in rats after CBD to minimal recovery of the Hering-Breuer inflation reflex in ponies after LD. The degree of plasticity varies among the different functions of each pathway, and plasticity varies with the age of the animal when the lesion was made. In addition, plasticity after some lesions varies between species, and plasticity is greater in the awake than in the anesthetized state. Reinnervation is not a common mechanism of plasticity. There is evidence supporting two mechanisms of plasticity. One is through upregulation of an alternate sensory pathway, such as serotonin-mediated aortic chemoreception after CBD. The second is through upregulation on the efferent limb of a reflex, such as serotonin-mediated increased responsiveness of phrenic motoneurons after CDR, TDR, and spinal cord injury. Accordingly, numerous components of the ventilatory control system exhibit plasticity after denervation or lesion-induced changes in breathing; this plasticity is uniform neither in magnitude nor in underlying mechanisms. A major need in future research is to determine whether "reorganization" within the central nervous system contributes to plasticity following lesion-induced changes in breathing.receptors; recovery of function; redundancy; chemoreflexes; mechanoreflexes DENERVATION OR LESIONING OF a receptor or neural pathway that normally contributes to the regulation of a physiological function will result in loss of or altered function. Thereafter, a time-dependent recovery of function is a manifestation of plasticity within the regulatory system. The purpose of this review is to summarize research on this type of plasticity within the system regulating breathing. Lesions are one of several means of inducing plasticity; a review of these and a general discussion of plasticity are presented elsewhere (66). Nevertheless, it seems appropriate to emphasize here that recovery of function can be due to restoration of the same mechanism or substitution of another mechanism. Also, recovery refers specifically to the return of a function, whereas plasticity refers to the process or mechanism of the restoration (i.e., capability of building new tissue or formative). A related phenomenon, redundancy, refers to two or more mechAddress for reprint requests and other correspondence:

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“…Although no clear physiologic role for these carotid body monoamines has been established, recent studies have demonstrated that dopamine may act as an inhibitor of carotid bodies chemosensitivity (22)(23)(24). Exogenous catecholamines can change the sensitivity of chemoreceptors to hypoxia and hypercapnia (25), which might be due to an action on excitatory and inhibitory dopaminergic receptors (26). One might speculate that the absence of a terbutaline effect on the respiratory response to LCR stimulation in the younger lambs shortly after birth is related to the presence of already high catecholamine concentrations in their carotid bodies.…”

Section: O-l_l-----'lllj"--------'--_jmentioning

confidence: 99%

Effects of Carotid Body Maturation and Terbutaline on the Laryngeal Chemoreflex in Newborn Lambs

et al. 1986

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ABSTRACf. The response to laryngeal chemoreflex (LCR) water stimulation was compared in unanesthetized awake 4-to 10-day-old preterm and 2-to 4-wk-old term lambs before and after infusion of a ,B-adrenergic agonist, terbutaline, given pre-and postcarotid body denervation (CBD). Ventilation decreased more in response to LCR stimulation post-CBD in the older lambs. CBD did not change the respiratory response to LCR stimulation in the younger lambs. LCR stimulation resulted in less bradycardia post-CBD in both groups. Terbutaline significantly attenuated the LCR response in the older lambs pre-CBD but not post-CBD. LCR respiratory response was not changed in the younger lambs when terbutaline was infused, pre-or post-CBD. Compared to wakefulness, the LCR response in preterm lambs was greater in sleep not associated with arousal. If arousal occurred, LCR response during sleep did not differ from that during wakefulness. The incidence of arousal decreased markedly after CBD, suggesting that arousal is modified by the carotid bodies. It is concluded that the carotid bodies modify the reflex response to LCR stimulation in 2-to 4-wk-old lambs. During the 1st postnatal wk, preterm lambs have a reduced carotid body function during wakefulness and, therefore, a decreased hypoxic ventilatory response and increased respiratory response to LCR stimulation. The attenuating effect of terbutaline on LCR response is partially related to mature carotid body function. (Pediatr Res 20: 724-729, 1986) Abbreviations CBD, carotid body denervation LCR, laryngeal chemoreflex Reflex apnea from stimulation ofthe LCR has previously been described in several animal species (1-3) and in human infants (4). The reflex is thought to be a protective mechanism through which animals and humans can preserve vital functions while they are not breathing. Laryngeal water stimulation elicits apnea, swallowing, hypertension, bradycardia, and blood flow redistribution in the "diving seal" pattern (2, 5). The respiratory response is associated with a decrease in arterial oxygen tension which should stimulate arterial chemoreceptors. In a previous study (2), we demonstrated a decrease in the cardiovascular response to Received April 15, 1985; accepted March 17, 1986. Correspondence and reprint requests should be addressed to Dr. Jens Grogaard, Department of Pediatrics, Vanderbilt University, School of Medicine, Nashville, TN 37232.This research was supported by grants from the National Institute of Health (RR 5424-21 and HL 14214) and March of Dimes Birth Defects Foundation (1-739).LCR stimulation during hyperoxia and proposed that part of the cardiovascular response to laryngeal water administration in newborn lambs might be due to stimulation of arterial chemoreceptors. Postnatal age appears to be an important factor in the LCR response. The respiratory response to LCR stimulation is markedly diminished in the adult animal compared to the newborn of the same species (3). A postnatal maturation effect has been demonstrated on the carotid body mediated ...

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Hypoventilation in ponies after carotid body denervation

Cited by 58 publications

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Carotid body function and ventilatory responses in intermittent hypoxia. evidence for anomalous brainstem integration of arterial chemoreceptor input

Carotid body function and ventilatory responses in intermittent hypoxia. evidence for anomalous brainstem integration of arterial chemoreceptor input

Invited Review: Plasticity in the control of breathing following sensory denervation

Effects of Carotid Body Maturation and Terbutaline on the Laryngeal Chemoreflex in Newborn Lambs

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