Ventilatory response to drug-induced hypermetabolism

1975 ◽  
Vol 38 (5) ◽  
pp. 827-833 ◽  
Author(s):  
S. Levine ◽  
W. E. Huckabee

Previous workers have demonstrated that an increase in minute ventilation accompanies tissue hypermetabolism induced by uncouplers of oxidative phosphorylation. The mechanism of this increase in minute ventilation has not been established. Accordingly, 2.5 mg/kg of 2,4-dinitrophenol (DNP) or 8–15 mg/kg of ethyl methylene blue (EMB) were infused into chloralose-anesthetized mongrel dogs; Vo2 increased 105 plus or minus 3% and VE INCREASED 107 PLUS OR MINUS 14%. Heads of vagotomized dogs were then perfused entirely with normal unchanging blood. Spinal cord remained intact. (The carotid bodies lay within the region of the perfused head.) Ventilatory responses of these head-perfused animals to breathing low oxygen and to breathing high CO2 gas mixtures were greatly attenuated. However, when DNP or EMB was infused into the body, VO2 increased 114 plus or minus 23% and VE increased 123 plus or minus 22%. When similar doses of DNP or emb were selectively administered to the head, increases in VE were limited to 21 plus or minus 6%. It is concluded that a major portion of the stimulus to ventilation, which accompanies infusion of DNP or of EMB, arises in tissues other than arterial chemoreceptors and brain. Presumably, this ventilatory stimulus is transmitted to the respiratory center via afferent pathways of the cervical spinal cord.

2019 ◽  
Vol 126 (1) ◽  
pp. 111-123 ◽  
Author(s):  
Kun-Ze Lee

The present study was designed to investigate breathing patterns across the sleep-wake state following a high cervical spinal injury in rats. The breathing patterns (e.g., respiratory frequency, tidal volume, and minute ventilation), neck electromyogram, and electroencephalography of unanesthetized adult male rats were measured at the acute (i.e., 1 day), subchronic (i.e., 2 wk), and/or chronic (i.e., 6 wk) injured stages after unilateral contusion of the second cervical spinal cord. Cervical spinal cord injury caused a long-term reduction in the tidal volume but did not influence the sleep-wake cycle duration. The minute ventilation during sleep was usually lower than that during the wake period in uninjured animals due to a decrease in respiratory frequency. However, this sleep-induced reduction in respiratory frequency was not observed in contused animals at the acute injured stage. By contrast, the tidal volume was significantly lower during sleep in contused animals but not uninjured animals from the acute to the chronic injured stage. Moreover, the frequency of sigh and postsigh apnea was elevated in acutely contused animals. These results indicated that high cervical spinal contusion is associated with exacerbated sleep-induced attenuation of the tidal volume and higher occurrence of sleep apnea, which may be detrimental to respiratory functional recovery after cervical spinal cord injury. NEW & NOTEWORTHY Cervical spinal injury is usually associated with sleep-disordered breathing. The present study investigated breathing patterns across sleep-wake state following cervical spinal injury in the rat. Unilateral cervical spinal contusion significantly impacted sleep-induced alteration of breathing patterns, showing a blunted frequency response and exacerbated attenuated tidal volume and occurrence of sleep apnea. The result enables us to investigate effects of cervical spinal injury on the pathogenesis of sleep-disordered breathing and evaluate potential therapies to improve respiration.


2001 ◽  
Vol 91 (6) ◽  
pp. 2451-2458 ◽  
Author(s):  
Francis J. Golder ◽  
Paul J. Reier ◽  
Paul W. Davenport ◽  
Donald C. Bolser

The mechanisms by which chronic cervical spinal cord injury alters respiratory function and plasticity are not well understood. We speculated that spinal hemisection at C2 would alter the respiratory pattern controlled by vagal mechanisms. Expired volume (Ve) and respiratory rate (RR) were measured in anesthetized control and C2-hemisected rats at 1 and 2 mo postinjury. C2 hemisection altered the pattern of breathing at both postinjury time intervals. Injured rats utilized a higher RR and lower Ve to maintain the same minute ventilation as control rats. After bilateral vagotomy, the pattern of breathing in injured rats was not different from controls. The frequency of augmented breaths was higher in injured rats at 2 mo postinjury before vagotomy; however, the Ve of augmented breaths was not different between groups. In conclusion, C2 hemisection alters the pattern of breathing at 1 and 2 mo postinjury via vagal mechanisms.


1976 ◽  
Vol 41 (5) ◽  
pp. 639-645 ◽  
Author(s):  
S. Levine

To explore the possibility that salicylates can stimulate VE via an extracranial mechanism, heads of dogs were perfused entirely by a support dog with blood of unchanging gas composition; spinal cord remained intact. The carotid bodies lay within the region of the perfused head; the aortic bodieswere denervated. Intra-arterial infusion of sodium salicylate (150–225 mg/kg) into the body of these head-perfused animals elicited large increases inVE (188+/-11%), although significant amounts of salicylate did not reach the head or carotid body. In any case, when the same dose of salicylate was selectively administered to the head, increases in VE were limited to23+-8%. To determine the contribution of thoracic receptors to the increasein VEelicited by salicylates, a subsequent group of head-perfused animals underwent complete spinal transection at the first lumbar level. Nnetheless,intra-arterial infusion of sodium salicylate (150–225 mg/kg) into the body of these head-perfused animals still elicited large increases in VE (111+/-13%). It is concluded that thoracic receptors (other than the aorticbodies) mediate a significant portion of the increase in VE elicited by intra-arterial infusion of sodium salicylate.


1985 ◽  
Vol 59 (6) ◽  
pp. 1752-1756 ◽  
Author(s):  
J. S. Kelling ◽  
A. F. DiMarco ◽  
S. B. Gottfried ◽  
M. D. Altose

This study compared the respiratory responses to ventilatory loading in 8 normal subjects and 11 quadriplegic patients with low cervical spinal cord transection. Progressive hypercapnia was produced by rebreathing. Rebreathing trials were carried out with no added load and with inspiratory resistive loads of 5 and 16 cmH2O. l-1 X s. Measurements were made of ventilation and of diaphragmatic electromyographic activity. Base-line hypercapnic ventilatory responses were significantly lower than normal in the quadriplegic patients, but the effects of resistive loading on the ventilatory responses were comparable in the two groups. The change in peak moving-average diaphragmatic electrical activity (DI peak) for a given change in CO2 partial pressure (PCO2) and DI peak at PCO2 55 Torr increased significantly with resistive loading both in the normal subjects and the quadriplegic patients. In the normal subjects, but not in the quadriplegic patients, inspiratory duration increased progressively with increasing resistance. The increase in DI peak during ventilatory loading in the normal subjects was a consequence of inspiratory prolongation. In contrast, in the quadriplegic patients during breathing against the larger resistive load, there was a significant increase in the average rate of rise (DI peak divided by the time from onset to peak) of diaphragmatic activity. The change in DI rate of rise for a given change in PCO2 increased to 137 +/- 13% (SE), and the DI rate of rise at PCO2 55 Torr increased to 128 +/- 8% (SE) of control values. These results indicate that compensatory increases in diaphragmatic activation during ventilatory loading occur in quadriplegic patients in whom afferent feedback from rib cage receptors is disrupted.


2004 ◽  
Vol 97 (4) ◽  
pp. 1401-1407 ◽  
Author(s):  
Masahiko Izumizaki ◽  
Mieczyslaw Pokorski ◽  
Ikuo Homma

We examined the effects of carotid body denervation on ventilatory responses to normoxia (21% O2 in N2 for 240 s), hypoxic hypoxia (10 and 15% O2 in N2 for 90 and 120 s, respectively), and hyperoxic hypercapnia (5% CO2 in O2 for 240 s) in the spontaneously breathing urethane-anesthetized mouse. Respiratory measurements were made with a whole body, single-chamber plethysmograph before and after cutting both carotid sinus nerves. Baseline measurements in air showed that carotid body denervation was accompanied by lower minute ventilation with a reduction in respiratory frequency. On the basis of measurements with an open-circuit system, no significant differences in O2 consumption or CO2 production before and after chemodenervation were found. During both levels of hypoxia, animals with intact sinus nerves had increased respiratory frequency, tidal volume, and minute ventilation; however, after chemodenervation, animals experienced a drop in respiratory frequency and ventilatory depression. Tidal volume responses during 15% hypoxia were similar before and after carotid body denervation; during 10% hypoxia in chemodenervated animals, there was a sudden increase in tidal volume with an increase in the rate of inspiration, suggesting that gasping occurred. During hyperoxic hypercapnia, ventilatory responses were lower with a smaller tidal volume after chemodenervation than before. We conclude that the carotid bodies are essential for maintaining ventilation during eupnea, hypoxia, and hypercapnia in the anesthetized mouse.


2021 ◽  
Vol 11 ◽  
Author(s):  
Mattia Pozzato ◽  
Emanuele Micaglio ◽  
Chiara Starvaggi Cucuzza ◽  
Alessandro Cagol ◽  
Daniela Galimberti ◽  
...  

Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disease characterized by recurrent episodes of fever and serositis caused by mutations in the MEFV gene, while Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the CNS with genetic and environmental etiology. The two diseases rarely occur in association with relevant implications for clinical management and drug choice. In this paper, we present the case of a 53-year-old male with an autosomal dominant FMF since childhood who presented acute paresthesia at the right part of the body. He performed a brain and spinal cord MRI, which showed multiple brain lesions and a gd-enhancing lesion in the cervical spinal cord, and then received a diagnosis of MS. He then started Interferonβ-1a which was effective but not tolerated and caused hepatotoxicity, and then shifted to Rituximab with 3-month clinical and neuroradiological efficacy.


1976 ◽  
Vol 39 (3) ◽  
pp. 564-581 ◽  
Author(s):  
B. W. Peterson ◽  
J. I. Franck ◽  
N. G. Daunton

1. In cats anesthetized with chloralose, responses of medial pontomedullary reticular neurons to stimulation of the body surface, vestibular nerves, superior colliculi, pericruciate cortices, cerebral peduncles, and spinal cord were studied at different stimulus rates. Raising the rate from 1/10 s to between 1/4 s and 2/s caused a significant decrement or increment in the response of most neurons tested. Response decrement typically began near the beginning of the higher frequency stimulus sequence and increased throughout the sequence. Response increment usually began somewhat later, rose to a peak, and then declined. Recovery from response decrement or increment usually occurred within 30-60 s at a 1/10 s stimulus rate.2. Measurements of response latency and of changes occurring in the initial and longer latency portions of responses indicated that all components of a response typically decreased or increased in parallel. Background spontaneous activity did not change during response decrements, but sometimes increased during response increment.3. Where changes could be detected, response decrement usually developed more rapidly when a sequence of repetitive stimulation was repeated.4. Response decrement was most pronounced at the highest stimulation rates and lowest stimulus intensities. Response increment was usually maximal at a stimulus rate of 1/s: at lower rates less increment occurred; at higher rates responses began to exhibit decrement.5. Response changes varied with the type of stimulus applied. Response decrements predominated when the body surface, vestibular nerves, or ipsilateral superior colliculus were stimulated. Approximately equal amounts of response increment and decrement were produced by repetitive stimulation of the cerebral peduncles and contralateral superior colliculus. Stimulation of the surface of the pericruciate cortex or of the spinal cord usually produced a long-lasting response increment.6. Generalization of response decrement and increment was observed in cases where trains of stimuli at a rate of 2/s applied to one point produced changes in the response to stimulation of another point which was tested once per 10 s and where single-shock stimulation of the first point was without effect on the test response. Generalization of response decrement occurred most often when two nearby points were stimulated. Generalization of response increment appeared to spread widely between distant cutaneous points and stimuli of different kinds.7. The response decrement and increment observed in medial pontomedullary reticular neurons displayed most of the parametric features of behavioral habituation and sensitization (8, 33) and therefore appear to represent neural analogs of these latter phenomena. The properties of response decrement suggest that it may occur to a large extent within afferent pathways leading to medial reticular neurons...


1994 ◽  
Vol 77 (5) ◽  
pp. 2231-2236 ◽  
Author(s):  
D. Gozal ◽  
R. Arens ◽  
K. J. Omlin ◽  
S. L. Ward ◽  
T. G. Keens

Abnormalities in ventilatory control during wakefulness and sleep have been observed in patients with Prader-Willi syndrome (PWS). The role of peripheral chemoreceptors in the pathophysiology of abnormal ventilatory responses in PWS is unknown. We studied peripheral chemoreceptor function during wakefulness in 17 genetically confirmed PWS patients [age 27.0 +/- 2.5 (SE) yr; 7 males, 10 females; body mass index 31.1 +/- 1.4 kg/m2] and compared their responses with 17 control subjects matched for age, sex, and body mass index. All PWS and control subjects had normal resting end-tidal PCO2 and arterial O2 saturation while awake. Peripheral chemoreceptor function was assessed by the ventilatory responses to 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 15% CO2 in O2. Control subjects decreased minute ventilation (VE) by 15.5 +/- 3.6% during hyperoxia. However, PWS patients increased VE by 17.6 +/- 3.3%, indicating a paradoxical response to hyperoxia (P < 0.00001). After CO2 vital capacity breaths, PWS patients showed no significant change and control subjects showed a marked increase (P < 0.0001) in VE. During N2 breathing, again PWS patients showed no change and control subjects exhibited a marked increase (P < 0.00005) in VE. We conclude that PWS patients have absent peripheral chemoreceptor ventilatory responses. We speculate that the lack of ventilatory responses is due to primary peripheral chemoreceptor dysfunction and/or defective afferent pathways to central controllers.


1989 ◽  
Vol 67 (5) ◽  
pp. 2006-2013 ◽  
Author(s):  
T. Morikawa ◽  
Y. Ono ◽  
K. Sasaki ◽  
Y. Sakakibara ◽  
Y. Tanaka ◽  
...  

The ventilatory and cardiac responses to voluntary and passive exercise were studied in 20 healthy subjects. These responses to passive leg exercise were also studied in 23 patients with spinal cord transection at the level of T5-T12. In the normal subjects, minute ventilation (VE) increased abruptly from the first breath after the onset of the two types of exercise. In contrast, cardiac output (Q) increased gradually in voluntary exercise, exhibiting significant augmentation from the fifth breath. Q changed insignificantly in passive exercise. In the patients with spinal cord transection, neither VE nor Q changed with passive exercise. These results suggest that ventilatory responses at the onset of mild exercise are related to drives from the moving limbs. We could not detect any evidence to support cardiodynamic hyperpnea at the onset of exercise.


2008 ◽  
Vol 62 (suppl_1) ◽  
pp. ONS226-ONS234 ◽  
Author(s):  
Ahmed M. Raslan

Abstract Objective: The author presents data to support the continued need for ablative procedures, particularly cordotomy, in the management of cancer-related pain. Methods: Fifty-one patients with cancer-related body or face pain were treated with computed tomography-guided radiofrequency ablation of the spinothalamic tract or trigeminal tract nucleus in the upper cervical region of the spinal cord. Forty-one patients underwent a unilateral cervical cordotomy, and 10 patients underwent a trigeminal tractotomy–nucleotomy. Three methods to assess patient pain were used: degree of pain relief, Visual Analog Scale, and total sleeping hours. The Karnofsky scale was used to measure the patient's level of function pre- and postprocedure. Results: After surgical intervention, patients reported initial and 6-months follow-up pain relief as 98 and 80%, respectively. Conclusion: Computed tomography-guided ablation of the upper cervical spinal cord is a safe and effective procedure to treat cancer pain involving the body or face. There remains a need for ablative procedures, in particular cordotomy, in the management of cancer-related pain.


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