Decrease In Ventilatory Response Research Articles

Influence of Step Frequency on the Dynamic Characteristics of Ventilation and Gas Exchange During Sinusoidal Walking in humans

We tested the hypothesis that restricting either step frequency (SF) or stride length (SL) causes a decrease in ventilatory response with limited breath frequency during sinusoidal walking. In this study, 13 healthy male and female volunteers (mean ± SD; age: 21.5 ± 1.8 years, height: 168 ± 7 cm, weight: 61.5 ± 8.3 kg) participated. The walking speed was sinusoidally changed between 50 and 100 m⋅min–1 with periods from 10 to 1 min. Using a customized sound system, we fixed the SF at 120 steps⋅min–1 with SL variation (0.83–0.41 m) (SFfix) or fixed the SL at 0.7 m with SF variation (143–71 steps⋅min–1) (SLfix) during the subjects’ sinusoidal walking. Both the subjects’ preferred locomotion pattern without a sound system (Free) and the unprompted spontaneous locomotor pattern for each subject (Free) served as the control condition. We measured breath-by-breath ventilation [tidal volume (VT) and breathing frequency (Bf)] and gas exchange [CO2 output (CO2), O2 uptake (O2)]. The amplitude (Amp) and the phase shift (PS) of the fundamental component of the ventilatory and gas exchange variables were calculated. The results revealed that the SFfix condition decreased the Amp of the Bf response compared with SLfix and Free conditions. Notably, the Amp of the Bf response under SFfix was reduced by less than one breath at the periods of 5 and 10 min. In contrast, the SLfix condition resulted in larger Amps of Bf and E responses as well as Free. We thus speculate that the steeper slope of the E-CO2 relationship observed under the SLfix might be attributable to the central feed-forward command or upward information from afferent neural activity by sinusoidal locomotive cadence. The PSs of the E, O2, and CO2 responses were unaffected by any locomotion patterns. Such a sinusoidal wave manipulation of locomotion variables may offer new insights into the dynamics of exercise hyperpnea.

The influence of opioids and nonopioid central nervous system active medications on central sleep apnea: a case-control study.

Opioids are known to contribute to central sleep apnea (CSA), but the influence of nonopioid central nervous system active medications (CNSAMs) on CSA remains unclear. In light of the hypothesized impact of nonopioid CNSAMs on respiration, we examined the relationships between the use of opioids only, nonopioid CNSAMs alone, and their combination with CSA. Among all adults who underwent polysomnography testing at the University of Michigan's sleep laboratory between 2013 and 2018 (n = 10,606), we identified 212 CSA cases and randomly selected 300 controls. Participants were classified into four groups based on their medication use: opioids alone, nonopioid CNSAMs only, their combination, and a reference group, including those who did not use any of these medications. We defined CSA as a binary outcome and as a continuous variable using central apnea index data. Logistic and linear regression were used to examine associations between medication use, CSA diagnosis, and central apnea index. Study participants included 58% men, and mean age was 50 (± 14 standard deviation years. Nearly half of the study participants did not use opioids or nonopioid CNSAMs, 6% used opioids alone, 27% nonopioid CNSAMs alone, and 16% used a combination of these medications. In adjusted analyses, opioids-only users had a nearly twofold increase in CSA odds, whereas those who used a combination of opioids and nonopioid CNSAMs had fivefold higher odds of CSA relative to the reference group. In contrast, the use of nonopioid CNSAMs alone had protective associations with CSA. This report showed increased odds of CSA, particularly among patients with sleep complaints who were prescribed opioids in combination with nonopioid CNSAMs compared with those who did not use any of these medications.

Lack of correlation between the ventilatory response to CO2 and lung function impairment in myotonic dystrophy patients: Evidence for a dysregulation at central level

Myotonic dystrophy Type 1 (DM1) is the most common muscular dystrophy in adults. Respiratory failure is common but clinical findings support a dysregulation of the control of breathing at central level, furthermore contributing to alveolar hypoventilation independently of the severity of respiratory weakness. We therefore intended to study the relationship between the ventilatory response to CO2 and the impairment of lung function in DM1 patients. Sixty-nine DM1 patients were prospectively investigated (43.5 ± 12.7 years). Systematic pulmonary lung function evaluation including spirometry, plethysmography, measurements of respiratory muscle strength, arterial blood gas analysis and ventilatory response to CO2 were performed. Thirty-one DM1 patients (45%) presented a ventilatory restriction, 38 (55%) were hypoxaemic and 15 (22%) were hypercapnic. Total lung capacity decline was correlated to hypoxaemia (p = 0.0008) and hypercapnia (p = 0.0013), but not to a decrease in ventilatory response to CO2 (p = 0.194). Ventilatory response to CO2 was reduced to 0.85 ± 0.67 L/min/mmHg and not correlated to respiratory muscle weakness. Ventilatory response to CO2 was neither different among restricted/non-restricted patients (p = 0.2395) nor among normoxaemic/hypoxaemic subjects (p = 0.6380). The reduced ventilatory response to CO2 in DM1 patients appeared independent of lung function impairment and respiratory muscle weakness, suggesting a central cause of CO2 insensitivity.

Effect of sustained hypoxia on ventilatory response to CO2 in normal adults

In adult humans the ventilatory response to sustained hypoxia is biphasic, characterized by an early increase followed by a decline to an intermediate plateau. Recently, we have shown that this decrease in hypoxic sensitivity is long lasting, because up to 1 h of room air breathing is required for complete recovery of the initial hypoxic response (J. Appl. Physiol. 64: 521-528, 1988). It is not known whether this posthypoxia decrease in ventilatory response is general or specific only to hypoxic stimuli. We therefore examined responses to CO2 before and after hypoxia. The ventilatory response to 5 min of normoxic CO2 breathing was evaluated in eight normal adults on 2 days: 5 min before and after 25 min of normocapnic hypoxia (arterial O2 saturation +/- 80%) and 5 min before and after 25 min of room air breathing (control day). During hypoxia, ventilation (VI), after an initial increase, declined significantly. At the end of hypoxia, abrupt exposure to room air transiently dropped VI to values that were significantly below base line. On each experimental day, the first and second exposure to CO2 increased ventilation by a similar amount, averaging, respectively, 8.46 +/- 0.9 and 8.84 +/- 0.92 (SE) l/min on the hypoxic day and 8.24 +/- 0.96 and 7.65 +/- 0.94 l/min on the control day. All the hypercapnic increases of VI were accomplished through similar changes of breathing pattern with similar time courses. We conclude that sustained hypoxia does not affect the ventilatory response to CO2, but it selectively depresses hypoxic sensitivity.

Ventillatory response of the conscious or anesthetized cat to oxygen breathing

In conscious intact cats, oxygen breathing for up to 1 h does not modify ventilation, and the ventilatory response to CO 2 in hyperoxia is not consistently decreased. However, oxygen breathing induces sustained hyperventilation in conscious cats after carotid body denervation. In anesthetized ctas, oxygen breathing provokes a hypoventillation which is transient under light anesthesis but more sustained under deeper levels of anesthesia. At all levels of anesthesia, the ventilatory response to CO 2 is decreased in hyperoxia as compared with normaxia. These results suggest that: (1) the effects of hyperoxia include a central stimulating component, seen only in conscious animals, which offsets the decreased ventilatory drive from peripheral chemoreceptors; (2) this central component is sensitive to anesthesia, thus allowing an explanation for the permanent decrease in ventilation and decrease in ventilatory response to CO 2 observed when oxygen is given during deep anesthesia; and (3) anesthesia may help to purposefully unmask factors involved in the control of breathing, but it markedly alters the normal functioning of the respiratory network.

Ventilatory responses to inspiratory flow-resistive loads in awake and sleeping dogs.

We studied ventilatory responses to inspiratory flow-resistive loads in six trained dogs, during quiet wakefulness and non-rapid-eye-movement (NREM) sleep. During studies dogs lay quietly in a lateral position and breathed through an endotracheal tube inserted via a chronic tracheostomy. Linear resistances of 6, 10, 19, and 31 cmH2O X l-1 X s were applied during inspiration for only a single breath to assess the immediate ventilatory response. The highest resistance was also applied for five successive breaths to assess the progressive ventilatory response. Ventilatory responses to hyperoxic progressive hypercapnia were also examined, with and without flow-resistive loading. During loading the maintenance of constant states of quiet wakefulness and NREM sleep was confirmed by electroencephalographic monitoring. Ventilation decreased on the first loaded breath and returned to control in a stepwise manner by the fifth loaded breath. No state-related differences were observed in either the immediate or progressive ventilatory responses. During CO2 rebreathing, the slope of the ventilatory response to CO2 was reduced by loading, with the reduction in slope (as percent of control) greater in the NREM state. We therefore conclude that in the dog immediate and progressive ventilatory responses to resistive loads are unaffected by NREM sleep, whereas the decrease in ventilatory response to CO2 resulting from loading tends to be greater in NREM sleep than in quiet wakefulness.

Effect of mechanical factors on respiratory work and ventilatory responses to carbon dioxide.

The end-tidal pCo2, mechanical work of breathing, and ventilation were determined in normal subjects breathing air, 2.2, 4.2 and 5.8 per cent Co2, with no added resistance and with three grades of added airway resistance. With increasing resistance, pCo2 and work rose in parallel whereas ventilation remained constant or even decreased. In the presence of a constant Co2 stimulus, increasing airway resistance caused a progressive decrease in ventilatory response to Co2. The maximum breathing capacity was not in itself the limiting factor in the ventilatory response to Co2. It is concluded that mechanical abnormalities of the respiratory apparatus are an important factor in reducing the ventilatory response to Co2, and that work of breathing is a more satisfactory index of respiratory stimulation than ventilation. Since patients with obstructive emphysema have nonelastic resistance values in the same range as those used in this study, it is concluded that the low ventilatory response to Co2 in these patients can, in large part, be explained by the mechanical abnormalities. Submitted on April 28, 1959