Increment In Ventilation Research Articles

Respiratory control during air-breathing exercise in humans following an 8h exposure to hypoxia

Hypoxic exposure lasting a few hours results in an elevation of ventilation and a lowering of end-tidal that persists on return to breathing air. We sought to determine whether this increment in ventilation is fixed (hypothesis 1), or whether it increases in proportion to the rise in metabolic rate associated with exercise (hypothesis 2). Ten subjects were studied on two separate days. On 1 day, subjects were exposed to 8 h of isocapnic hypoxia (end-tidal 55 Torr) and on the other day to 8 h of euoxia as a control. Before and 30 min after each exposure, subjects undertook an incremental exercise test. The best fit of a model for the variation in with metabolic rate gave a residual squared error that was ∼20-fold less for hypothesis 2 than for hypothesis 1 (p < 0.005, F-ratio test). We conclude that the alterations in respiratory control induced during early ventilatory acclimatization to hypoxia better reflect those associated with hypothesis 2 rather than hypothesis 1.

Simple exponential regression model to describe the relation between minute ventilation and oxygen uptake during incremental exercise.

The physiological significance of an exponential regression model between minute ventilation (VE) and oxygen uptake (VO2) during incremental exercise was examined. Thirty-eight subjects, including 12 patients with chronic heart failure, participated in cardiopulmonary exercise testing on a bicycle ergometer. The equation VE = a e(bVO2), where a and b are parameters, was used to describe the relation between VE and VO2 during incremental exercise. Arterialized blood gas analysis was measured before and during exercise. The correlation coefficient of the regression model was high (r = 0.97 +/- 0.02). Parameter a negatively correlated with the arterial partial pressure of carbon dioxide during exercise (r = -0.44, p < 0.01), and positively correlated with peak VO2 (r = 0.47, p < 0.01). Parameter b negatively correlated with peak VO2 (r = -0.86, p < 0.01) and positively correlated with the dead space to tidal volume ratio (r = 0.68, p < 0.01). The regression model, as well as parameters a and b, is physiologically useful in expressing metabolic response to exercise. This model, a specific solution to the differential equation dVE/dVO2 = bVE, implies that the more a subject breathes, the greater is the increment in ventilation needed to meet a further increment of metabolic demand.

Ventilatory and circulatory responses at the onset of rapid changes in posture.

The transition from rest to light or moderate intensity exercise is typically accompanied by an abrupt step-like increment in ventilation at the first exercise breath. This phase I response is observed during not only voluntary exercise and passive movement, but also during electrically induced muscle contraction. Many investigators have pursued the mechanisms of this phase I response; however, it is still a matter of dispute as to its nature. Since changes in ventilation are so rapid, a number of neural mechanisms, such as reflexogenic influences from the cerebral cortex and hypothalamic motor regions, afferent stimulus through the group III and IV fibers, and central and/or peripheral circulatory influences, are postulated to explain the phase I response.1 Regarding the last factor, Huszczuk et al.2 suggested that ventilation is controlled by a mechanism which acts rapidly, and which relies on the integrity of baroreception and/or vasoregulation; baroreception appears to be more important. Although it has been reported that hemodynamic responses are considerably affected by a sudden change in posture, it is likely that respiratory response is also modified by postural changes in man. To our knowledge, however, the initial ventilatory responses to rapid change in posture have not been studied in detail. The purpose of this study was to clarify the ventilatory and circulatory responses at the onset of sudden tilts from supine to upright, and vice versa.KeywordsVentilatory ResponseMuscle Sympathetic Nerve ActivityMean Blood PressureCirculatory ResponseVoluntary ExerciseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

運動開始時における換気応答

When exercise starts, various cardiorespiratory adjustments take place for accommodating the greatly increased metabolic requirements. It is well known that the transition from rest to light or moderate intensity exercise is typically accompanied by an abrupt step-1ike increment in ventilation at the first exercise breath. This rapid increment of ventilation at the onset of exercise (phase I) is observed during not only voluntary and passive exercise, but also during electrically induced muscle contraction. A rapid response in ventilation (phase I) may be at least useful for preventing oxygen deficiency and for increasing alveolar ventilation, oxygen tension, and oxygen uptake even if it is a small quantity. Although mechanisms of phase I have extensively been explored by many investigators, they have still remained obscure until now. At present, the causal factors of phase I are classified as central (descending) and peripheral (ascending) neurogenic stimulus, or as both. In the awake condition, abrupt ventilatory increment immediately after voluntary and passive exercise in man could be attributed to the drives from the central command including cortical and hypothalamic activities as well as some peripheral afferent information mainly through group III and IV fibers. However, further investigation to clarify many unsolved problems regarding neurogenic mechanisms of phase I should be advanced in future.

Ventilatory response to CO 2 and hypoxia during cold exposure in awake rats

Recently, we have described the effects of hypoxia and of hypercapnia on the metabolic (V̇ O 2 ) and ventilatory responses to cold in unanesthetized intact and carotid body-denervated (CBD) rats (Gautier et al., J. Appl. Physiol. 73: 847–854, 1992 and 75: 2570–2579, 1993). In the present paper, we have reanalyzed the above results for a more detailed study of the interactions of hypoxia (F i O 2 = 0.12), hypercapnia (F i CO 2 = 0.04) and changes in V̇ O 2 with the ventilatory control. The results show that: (1) Compared to normoxia, in hypoxia increments in V̇ and V t are proportional to V̇ O 2 whereas in hypercapnia increments in ventilation (V̇) and tidal volume (V t) are independent of V̇ O 2 . In both hypoxia and hypercapnia, increases in respiratory frequency (f r) are independent of V̇ O 2 ; and (2) Interactions of hypoxia, hypercapnia and V̇ O 2 with control of V̇ persist in CBD rats but, for a given V̇ O 2 , V̇, V t and f r are lower than in intact rats. These interactions are essentially similar to those observed during muscular exercise performed in normoxia, hypoxia or hypercapnia. It is suggested that during cold exposure or muscular exercise, resulting both in increased V̇ O 2 , there are common integrative structures probably located in the hypothalamus which are involved in the control of breathing.

Effects of haloperidol and domperidone on ventilatory roll off during sustained hypoxia in cats.

In a previous work, we showed that the adult cat demonstrates a ventilatory decline during sustained hypoxia (the "roll off" phenomenon) and that the mechanism responsible for this secondary decrease in ventilation lies within the central nervous system (J. Appl. Physiol. 63: 1658-1664, 1987). In this study, we sought to determine whether central dopaminergic mechanisms could have a role in the roll off. We studied the effects of haloperidol, a peripheral and centrally acting dopamine receptor antagonist, on the ventilatory response to sustained isocapnic hypoxia (end-tidal PO2 40-50 Torr, 20-25 min) in awake cats. In vehicle control cats (n = 5), sustained hypoxia elicited a biphasic respiratory response, during which an initial ventilatory stimulation is followed by a 24 +/- 6% (P less than 0.01) reduction. In contrast, in haloperidol- (0.1 mg/kg) treated cats (n = 5) the ventilatory roll off was virtually abolished (-1 +/- 1%; P = NS). We also measured ventilatory, carotid sinus nerve (CSN) and phrenic nerve (PhN) responses to sustained isocapnic hypoxia in anesthetized animals (n = 6) to explore the influence of haloperidol on peripheral and central response during the roll off. Control responses to hypoxia showed an initial increase in ventilation, PhN, and CSN activity, followed by a subsequent decline in ventilation and PhN activity of 17 +/- 3 and 17 +/- 5%, respectively (P less than 0.05). In contrast, CSN activity remained unchanged during the roll off. Administration of haloperidol (1 mg/kg) reduced the initial increment in ventilation, while the initial increase in CSN activity was augmented.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for phase-locking response to hypoxia in peripheral chemoreceptor activity in man.

A number of animal studies have demonstrated that the ventilatory response to stimulation of the peripheral chemoreceptors is well reproduced only when it is stimulated during inspiratory period. In humans, such a response has not been confirmed when using a mild hypoxic stimulus. We, therefore, hypothesized that this response may be detected when a more intense hypoxia is applied. To confirm this hypothesis, six healthy subjects inhaled N2 gas mixture with 5% CO2 in an amount of vital capacity. This procedure started from steady state mild hypoxia (PET02; 60-70 mmHg). Inspiratory and expiratory minute ventilation (VI and VE), tidal volume (VT), and inspiratory and expiratory time (TI and TE) of the breath, at the start of falling oxygen saturation, were analyzed. 21% O2 + 5% CO2 balanced with N2 was inhaled and a breath cycle with a similar latency as during N2 gas mixture inhalation was also analyzed as a control. When oxygen saturation began to drop at the inspiratory phase, the increment of ventilation and tidal volume were larger than the control. When it occurred at the expiratory phase, no significant difference from the control was seen. These results signify the presence of rectification of chemoreceptor afferent signal in humans and may support the concept of oscillation hypothesis as an effective ventilatory stimulus.

Changes of ventilation and ventilatory response to hypoxia during the menstrual cycle.

The relationship between change in hypoxic sensitivity in respiration, defined as increment in ventilation per drop of arterial O2 saturation (delta VE/delta SaO2), with the phase change from follicular to luteal and those in resting pulmonary ventilation (VE), mean inspiratory flow (VT/TI), alveolar partial pressures of CO2 and O2 (PACO2 and PAO2, respectively) and body temperature was studied in 10 women. There was a significant relationship between % increase in hypoxic sensitivity and decrement of resting PACO2 that occurred in the luteal phase. However, no significant relationships were observed between change in hypoxic sensitivity and those in the remaining parameters studied. The intersubject variation in % increase in resting VE during the luteal phase was not associated with that in % increase in hypoxic sensitivity. The results indicate that the contribution of increased hypoxic sensitivity to increasing VE during the luteal phase is variable among subjects. Reasons for the increase in hypoxic sensitivity with hypocapnia are discussed.

Ventilatory transients during exercise: peripheral or central control?

The fast component of the ventilatory changes that occur at the transition phases of exercise was studied in awake dogs trained to run on a treadmill. Two questions were examined: firstly, is the fast ventilatory component modified by changes in venous return to the lungs, such as those consecutive either to increased work loads or to beta adrenergic blockade?, and secondly, is this component altered by central ventilatory depressants? The results showed that at the onset of exercise, there is no correlation between the instantaneous increment in ventilation and the intensity of exercise, but at the end of the treadmill run, the fall in ventilation is closely linked to the power of the work performed. Ventilatory transients observed either at the start or at the end of exercise remain unaffected by administration of a beta-adrenergic blocking agent. But central depressant effects on ventilation caused by narcotic analgesics or hypnotic drugs altered the breathing pattern of the fast component of exercise-induced ventilatory changes. It is concluded that the instantaneous changes in ventilation occurring at the transition phases of exercise are controlled by mechanoreceptor mechanisms, but cerebral control is superimposed on the reflex control in regulating both tidal volume and breathing rate.

Attenuated ventilatory responses to hypercapnia and hypoxia in assisted breath-hold drivers (Funado).

The steady-state ventilatory responses to hypercapnia and hypoxia in 7 assisted breath-hold divers (Funado) were compared with those in 7 normal sedentary controls. Ventilatory response to hypercapnia was measured from the slope of the hyperoxic VN-PETCO2 line, where VN was normalized minute ventilation using the allometric coefficient and PETCO2 end-Tidal PCO2. The slope of this line in the Funado (1.48 +/- 0.54 liters . min-1 . Torr-1) was significantly less than in the control (2.70 +/- 1.08 liters . min-1 . Torr-1) (p less than 0.025). On the other hand, hypoxic sensitivity estimated by hyperbolic and exponential mathematical equations was not found to be significantly different between the two groups, although estimated increments in ventilation using the hyperbolic equation exhibited significantly lower response in the Funado than in the control only when PETO2 decreased lower than 50 Torr (p less than 0.05). These findings in the Funado were different from our previous observations obtained in unassisted breath-hold divers (Kachido), in whom no obvious attenuations in CO2 sensitivity were seen. This difference was assumed to be derived from more hypercapnic and hypoxic conditions produced in the Funado than in the Kachido during diving activities.

Effect of elastic loading on ventilatory response to hypoxia in conscious man

Ventilatory responses to isocapnic hypoxia, with and without an inspiratory elastic load (12.1 cmH2O/l), were measured in seven healthy subjects using a rebreathing technique. During each experiment, the end-tidal PCO2 was held constant using a variable-speed pump to draw gas from the rebreathing bag through a CO2 absorbing bypass. Studies with and without the load were performed in a formally randomized order for each subject. Linear regressions for rise in ventilation against fall in SaO2 were calculated. The range of unloaded responses was 0.74-1.38 1/min per 1% fall in SaO2 and loaded responses 0.71-1.56 1/min per 1% fall in SaO2. Elastic loading did not significantly alter the ventilatory response to progressive hypoxia (P greater than 0.2). In all subjects there was, however, a change in breathing pattern during loading, whereby increments in ventilation were attained by smaller tidal volumes and higher frequencies than in the control experiments. These results support the hypothesis previously proposed in our studies of resistive loading during progressive hypoxia, that a similar control pathway appears to be involved in response to the application of loads to breathing, whether ventilation is stimulated by hypoxia or hypercapnia.

Bicarbonate and the regulation of ventilation

The regulation of ventilation involves a multifactorial control system with several feedback loops transmitting deviations from normal in pH, carbon dioxide tension (pCO 2) and oxygen tension (pO 2) to the control area. Variations in the size of the bicarbonate pool, caused by ventilatory or metabolic disturbances, can be expected to modify resting ventilation if hydrogen ion activity is the ultimate stimulus of the regulation of ventilation. A relationship between serum bicarbonate and resting ventilation can be identified in patients with stable acid-base disturbances including those in whom correction of the arterial blood pH was not achieved by respiratory adaptation. Why the pH in arterial blood is rarely returned to the normal range is not well understood. It may be an inadequacy of the control system, a “compromise” solution avoiding hypoxia in metabolic alkalosis or increasing work of breathing in metabolic acidosis, or a consequence of discrepancies in hydrogen ion activity in body fluids adjacent to and remote from the control site. Additional information about the role of bicarbonate in the control of ventilation may be obtained by measuring the response to carbon dioxide inhalation at varying extracellular bicarbonate concentrations. The increments in ventilation during inhalation of carbon dioxide are within individual limitations, inversely and exponentially related to the bicarbonate concentrations in blood. These observations are in accord with the concept that the extracellular bicarbonate concentration modulates resting ventilation and the ventilatory response to inhalation of fixed concentrations of carbon dioxide by acting as a determinant for the hydrogen ion activity within or adjacent to the central chemosensitive control area.

Comparison of three methods for quantitating respiratory response to hypoxia in man

Three methods of quantitating the respiratory response to acute hypoxia were compared in nine normal young men: 1) Steady state CO 2 response at P O 2 = 200 and 40 torr. 2) Progressive hypoxia with PA CO 2 held at the subjects resting value and 5 torr- above this. 3) A single breath test which uses a single vital capacity inspiration of a hypoxic and/or hypercapnic gas and is presumed to stimulate primarily peripheral chemoreceptors. In methods 1 and 2 the ventilatory response to hypoxia (defined as the increment in ventilation produced by reduction of Pa O 2 from above 200 to 40 torr measured at the subjects' normal or standardized arterial P CO 2 ) averaged 19.9 and 20.9 L(min × m 2). Ventilation (mean of 2nd and 3rd spontaneous breaths) following a single vital capacity breath of 15% CO 2 in N 2 averaged 30.3 L(min × m 2) more than after a control breath of 5 % CO 2 on O 2. Hypoxic depression of ventilation occurred in 3 subjects during testing with method 1 and in 1 subject with method 2.

CNS DISORDER DURING MECHANICAL VENTILATION IN CHRONIC PULMONARY DISEASE.

Five patients with obstructive pulmonary disease developed generalized fits, coma, and multifocal central nervous system excitation following vigorous correction of chronic hypercapnia. Clinical improvement occurred prior to the onset of neurological symptoms. Alkalosis with persistent elevation of plasma bicarbonate concentration was the outstanding biochemical abnormality. Two patients recovered when their arterial CO 2 tensions were allowed to rise. Alkalosis should be avoided when treating pulmonary decompensation. Since hypoxia can be corrected rapidly by oxygen therapy, the hypercapnia can be corrected more gradually by successive increments in ventilation.

VENTILATORY RESPONSE TO INTERMITTENT INSPIRED CARBON DIOXIDE.

The hypothesis that cyclic variation of CO2 tension of the arterial blood (PaCOCO2) about its mean produces an additional stimulus to ventilation was tested in the dog. Oscillations of alveolar carbon dioxide tension were produced by the intermittent administration of 20% CO2 for 1 breath every 7–12 breaths. The increment in ventilation per mm Hg rise in mean PaCOCO2 during the intermittent administration of 20% CO2 was compared to that during continuous administration of 3% CO2 in nine adult dogs anesthesized with sodium pentobarbital. Thirteen experiments with oscillating CO2 and eighteen with steady CO2 were performed. In all except one animal the increase in ventilation per mm Hg change in mean PaCOCO2 was greater during intermittent CO2 than during steady CO2. In three experiments intermittent administration of CO2 caused a ventilatory response sufficient to lower the mean PaCOCO2 below control values. The increment in total ventilation per mm Hg rise in arterial carbon dioxide tension for steady CO2 breathing was 0.58 liters/min per mm Hg and for intermittent CO2 was 2.00 liters/min per mm Hg. These findings support the concept that chemoreceptors are stimulated by oscillations of PaCOCO2 as well as by the mean level of PaCOCO2. The oscillatory stimulus appears not to be related to the amplitude of the oscillation or to the peak Pco2 attained, but rather to the rate of increase of arterial Pco2. respiration control; ventilation Submitted on October 17, 1963

Respiratory control in uremic acidosis.

Lambertsen and co-workers were able to correlate increments in ventilation produced by a number of acute experimental acid-base derangements in man with combined shifts in H ion concentration in blood and cerebrospinal fluid. Comparing hyperventilation in a group of uremic acidotic patients with ventilation levels of a control group by the same criteria shows that the measured values in uremic subjects are lower than those predicted. The tentative conclusion may be drawn that in chronic renal failure the respiratory center is adapted to blood acidosis by an elevation of its threshold level for the H ion stimulus. Submitted on August 2, 1962

Breathing in brief exercise.

Two men ran for 20 or 60 seconds while inhaling air, oxygen or 4% carbon dioxide. Inspired respiratory minute volume was determined for each breath. Ventilation increased suddenly in the first breath with minimal changes in end-expiratory carbon dioxide tension and respiratory exchange ratio to a rate that remained constant for 20 seconds before increasing further. The rate of carbon dioxide output was uniform during the first 20 seconds. A 12% grade did not increase ventilation or oxygen uptake during runs of 20 seconds, but in the first minute of recovery, ventilation was 64% greater than after level runs. Inhalation of oxygen inhibited ventilation by 24% in the 20-second periods before and after the end of a 60-second run. Inhalation of carbon dioxide begun at rest produced increments in ventilation and end-expiratory carbon dioxide tension that varied little during running and recovery. In the 20-second runs ventilation varied with speed but appeared independent of ultimate metabolic cost. Submitted on January 21, 1960

Regulation of Respiration During Muscular Activity

The mechanism of exercise hyperpnea was investigated employing a cross-circulation technique in which the head of a dog (humoral dog) was perfused exclusively by blood from another dog (neural dog) by way of the carotid arteries and the external jugular veins. The lower extremities of both dogs were induced to exercise separately by stimulating with 60-cycle alternating current, which is modulated sinusoidally. Forty-four experiments were performed on nine pairs of such preparations. The ventilation of the neural dog (exercising) first overshot, then attained a steady state, but the ventilation of the humoral dog overshot to a much higher level when its hind legs were exercised. During the steady state the ventilation of the neural dog (when it was exercising) increased in direct proportion to oxygen consumption. The slope of the regression line expressing the increment in ventilation as a function of oxygen consumption in the neural dog is 0.0298, which is not statistically different from that established for intact dogs during induced exercise or from that in normal dogs during voluntary exercise. The humoral dog whose head was perfused by arterial blood from the exercising neural dog showed no change in ventilation. Therefore, it is concluded that there is no humoral agent produced in the arterial blood of a dog subjected to this type of exercise. The normalcy of the respiratory apparatus in the humoral dog after the establishment of the cross circulation was tested by CO2 inhalation and lobeline administration and it was found to be adequate.