Rate-modulated cardiac pacing based on transthoracic impedance measurements of minute ventilation: correlation with exercise gas exchange

The relation of pacing rate to physiologic variables of metabolic demand was examined in 10 consecutive patients with a minute ventilation-sensing, rate-modulating ventricular pacemaker implanted for complete heart block. All patients had paroxysmal (seven patients) or chronic (three patients) atrial fibrillation and were referred for catheter ablation of the atrioventricular junction. Treadmill exercise testing with measurement of expired gas exchange and respiratory flow was performed before ablation and 4 weeks after pacemaker implantation, with the pacemaker programmed to both the fixed-rate VVI and rate-modulating minute ventilation VVIR pacing modes in random sequence. The relation of pacing rate to oxygen consumption (VO2), expired carbon dioxide concentration (VCO2), respiratory quotient, tidal volume, respiratory rate and minute ventilation was determined during exercise in the rate-modulating minute ventilation pacing mode. Pacing rate was highly correlated with minute ventilation (r = 0.89), respiratory quotient (r = 0.89), VCO2 (r = 0.87), tidal volume (r = 0.87), VO2 (r = 0.84) and respiratory rate (r = 0.84). The mean exercise duration increased from 8.3 +/- 2.8 min in the fixed rate pacing mode to 10.2 +/- 3.4 min in the rate-modulating, minute ventilation mode (p = 0.0001). The maximal VO2 increased from 13.4 +/- 3.4 to 16.3 +/- 4.1 cc/kg per min (p = 0.0004). The maximal heart rate achieved in the minute ventilation pacing mode was 136 +/- 9.7 beats/min, similar to that observed in the patient's intrinsic cardiac rhythm before ablation (134.9 +/- 30.1 beats/min, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Protein kinase C modulates ventilatory patterning in the developing rat

Protein kinase C (PKC) mediates important components of signal transduction pathways underlying neuronal excitability and modulates respiratory timing mechanisms in adult rats. To determine ventilatory effects of systemic PKC inhibition during development, whole-body plethysmographic recordings were conducted in 2-3-d (n = 11), 5-6-d (n = 19), 10-12-d (n = 14), and 20-21-d-old (n = 14) rat pups after treatment with vehicle and Ro 32-0432 (100 mg/kg, intraperitoneally). Ro 32-0432 decreased minute ventilation (V E) by 51.0 +/- 5.5% (mean +/- SEM) in youngest pups (p < 0.01) but only 19.1 +/- 6.8% in 20-21-d-old pups (p < 0.01). V E decreases were always due to frequency reductions with tidal volume (VT) remaining unaffected. Respiratory rate decreases primarily resulted from marked expiratory time (TE) prolongations being more pronounced in 2-3-d-old (115.5 +/- 28.9%) compared with 20-21-d old (36.6 +/- 10.9%; p < 0.002 analysis of variance [ANOVA] ). Expression of the PKC isoforms alpha, beta, gamma, delta, iota, and mu was further examined in brainstem and cortex by immunoblotting and revealed different patterns with postnatal age and location. We conclude that endogenous PKC inhibition elicits age-dependent ventilatory reductions which primarily affect timing mechanisms rather than changes in volume drive. This effect on ventilation abates with increasing postnatal age suggesting that the neural substrate mediating overall respiratory output may be more critically dependent on PKC activity in the immature animal.     

Respiratory responses of piglets to hypercapnia during postnatal development: effects of opioids.

Resting respiratory and cardiovascular functions and the response to CO2 rebreathing were compared between 2.5 +/- 0.7 (mean +/- SE) and 34.1 +/- 1.9 day old piglets, before and after the opioid antagonist naltrexone (1 mg/kg IV). At rest, tidal volume, both absolute and per m2, inspiratory and expiratory time, absolute minute ventilation, and mean arterial pressure increased with age, and breathing frequency, minute ventilation per m2, and heart rate decreased, all of these with as well as without naltrexone. During hypercapnia, the pattern, but not the quantitative aspects of breathing changed with age. At rest, naltrexone produced hyperventilation in the young, but not in the older group. During hypercapnia, naltrexone had a sparse effect in both ages. We conclude that, in the anesthetized piglet, ventilatory functions at rest undergo change with postnatal age, but breathing responses to hypercapnia exhibit maturation in pattern only and not in magnitude. Whereas resting ventilation of young piglets is modulated by endogenous opioids, hypercapnia may activate opioids to a limited extent and in a manner unrelated to age.     

Normal values and ranges for ventilation and breathing pattern at maximal exercise

Assessment of the breathing pattern at maximal exercise in patients is limited because the range of ventilatory responses (minute ventilation; tidal volume; respiratory rate) at maximal exercise in normal humans is unknown. We studied 231 normal subjects (120 women; 111 men) equally distributed according to age from 20 to 80 years. Each subject performed a progressive incremental cycle ergometer exercise test to their symptom-limited maximum. Mean ventilation at the end of exercise (Vemax) was significantly higher in men (mean +/- SD, 97 +/- 25 L/min) than in women (69 +/- 22 L/min) (p less than 0.001). Minute ventilation at the end of exercise as a fraction of predicted maximal voluntary ventilation (Vemax/MVV) for all subjects was 0.61 +/- 0.14 (range, 0.28 to 1.02). There was no difference in Vemax/MVV between men (0.62 +/- 0.14) and women (0.59 +/- 0.14). Tidal volume at the end of exercise (Vtmax) was higher in men (2.70 +/- 0.48 L) than in women (1.92 +/- 0.41 L) (p less than 0.001). Any differences in Vtmax between men and women disappeared when Vtmax was corrected for baseline FVC. Respiratory rate at the end of exercise (RRmax) was 36.1 +/- 9.2 breaths per minute for all subjects. There was no difference in RRmax between men and women. The Vemax correlated best with carbon dioxide output at the end of exercise (r = 0.91; p less than 0.001) and with maximal oxygen uptake (r = 0.90; p less than 0.001) for all subjects. This study of a large group of subjects has demonstrated the wide range of possible breathing patterns which are adopted during exercise and has provided a wide range of "normal" responses which must be taken into consideration when maximal ventilatory data from exercise tests are analyzed.     

Effect of salmeterol on the ventilatory response to exercise in chronic obstructive pulmonary disease.

This study examined the effects of bronchodilator-induced reductions in lung hyperinflation on breathing pattern, ventilation and dyspnoea during exercise in chronic obstructive pulmonary disease (COPD). Quantitative tidal flow/volume loop analysis was used to evaluate abnormalities in dynamic ventilatory mechanics and their manipulation by a bronchodilator. In a randomised double-blind crossover study, 23 patients with COPD (mean +/- SEM forced expiratory volume in one second 42 +/- 3% of the predicted value) inhaled salmeterol 50 microg or placebo twice daily for 2 weeks each. After each treatment period, 2 h after dose, patients performed pulmonary function tests and symptom-limited cycle exercise at 75% of their maximal work-rate. After salmeterol versus placebo at rest, volume-corrected maximal expiratory flow rates increased by 175 +/- 52%, inspiratory capacity (IC) increased by 11 +/- 2% pred and functional residual capacity decreased by 11 +/- 3% pred. At a standardised time during exercise, salmeterol increased IC, tidal volume (VT), mean inspiratory and expiratory flows, ventilation, oxygen uptake (VO2) and carbon dioxide output. Salmeterol increased peak exercise endurance, VO2 and ventilation by 58 +/- 19, 8 +/- 3 and 12 +/- 3%, respectively. Improvements in peak VO2 correlated best with increases in peak VT; increases in peak VT and resting IC were interrelated. The reduction in dyspnoea ratings at a standardised time correlated with the increased VT. Mechanical factors play an important role in shaping the ventilatory response to exercise in chronic obstructive pulmonary disease. Bronchodilator-induced lung deflation reduced mechanical restriction, increased ventilatory capacity and decreased respiratory discomfort, thereby increasing exercise endurance.     

Sleep deprivation and the control of ventilation

Sleep deprivation is common in acutely ill patients because of their underlying disease and can be compounded by aggressive medical care. While sleep deprivation has been shown to produce a number of psychological and physiologic events, the effects on respiration have been minimally evaluated. We therefore studied resting ventilation and ventilatory responses to hypoxia and hypercapnia before and after 24 h of sleeplessness in 13 healthy men. Hypoxic ventilatory responses (HVR) were measured during progressive isocapnic hypoxia, and hypercapnic ventilatory responses (HCVR) were measured using a rebreathing technique. Measures of resting ventilation, i.e., minute ventilation, tidal volume, arterial oxygen saturation, and end-tidal gas concentrations, did not change with short-term sleep deprivation. Both HVR and HCVR, however, decreased significantly after a single night without sleep. The mean hypoxic response decreased 29% from a slope of 1.20 +/- 0.22 (SEM) to 0.85 +/- 0.15 L/min/% saturation (p less than 0.02), and the slope of the HCVR decreased 24% from 2.07 +/- 0.17 to 1.57 +/- 0.15 L/min/mmHg PCO2 (p less than 0.01). These data indicate that ventilatory chemosensitivity may be substantially attenuated by even short-term sleep deprivation. This absence of sleep could therefore contribute to hypoventilation in acutely ill patients.     

Assessment of tidal breathing parameters in infants with cystic fibrosis.

Simple methods are needed to assess lung function in infants with cystic fibrosis (CF). This study determined the relationship between simple measurements obtained from tidal breathing with those from more complicated forced expiratory manoeuvres. Healthy infants and infants with CF were recruited from two maternity units and five specialist CF hospitals, respectively. Respiratory rate, tidal volume, minute ventilation and the tidal breathing ratio (TPTEF:TE) were measured in sedated infants and compared with forced expiratory volume in 0.4 seconds (FEV0.4) measured by the raised volume technique. Altogether, 95 healthy infants and 47 infants with CF of similar age, sex, ethnicity and proportion exposed to maternal smoking were recruited. There was no difference in TPTEF:TE and tidal volume between healthy infants and those with CF. Minute ventilation was significantly greater in infants with CF due to a mean (95% confidence interval) increase in respiratory rate of 5.8 (3.2-8.4) min(-1). Thirteen (28%) infants with CF had a respiratory rate elevated by >2 SD. However, no association between respiratory rate and FEV0.4 could be identified. Tidal breathing ratio was not useful in identifying diminished airway function in infants with cystic fibrosis. An elevated respiratory rate may be due in part to ventilation heterogeneity but is poorly predictive of diminished airway function measured by forced expiration.     

Ventilatory regulation in eucapnic morbid obesity

In morbid obesity, there is an increased hindrance to breathing caused by the effects of the increased mass on the chest wall and abdomen; subjects with morbid obesity can maintain eucapnia by increasing inspiratory neuromuscular drive and/or by altering central breath timing. We studied 23 eucapnic, obese subjects (greater than 190% predicted ideal weight), 7 males and 16 females with a mean age of 36.6 +/- 9.2 yr and 18 healthy, normal male subjects. Total lung capacity, functional residual capacity, and total thoracic compliance were significantly (p less than 0.05) reduced in the obese subjects. At rest, minute ventilation was significantly increased because of an increase in respiratory frequency, which in turn was due to a significant decrease in the expiratory time (TE) per breath; the ratio of inspiratory to expiratory time (TI/TE) was thus significantly altered, indicating an alteration in central breath timing. Resting inspiratory neuromuscular drive (as represented by mouth occlusion pressure) was significantly increased in the obese subjects, but tidal volume was not significantly altered. There was an increased ventilatory responsiveness to hypoxia and relatively decreased ventilatory responsiveness to hypercapnia in the obese subjects. These results indicate that morbidly obese subjects maintain eucapnia primarily by an alteration in central breath timing. Although these subjects have decreased responsiveness to CO2, putting them at some risk of developing respiratory failure under conditions of hypercapnic/hypoxic stress, it is possible that this is counteracted by the increased responsiveness to hypoxia.     

Effects of hydralazine on mouth occlusion pressure and ventilatory response to hypercapnia in patients with chronic obstructive pulmonary disease and pulmonary hypertension

Hydralazine has been shown to increase minute ventilation (VE) in patients with chronic obstructive pulmonary disease and pulmonary hypertension. The mechanism by which hydralazine produces this effect has not been defined. We investigated the effects of orally administered hydralazine on hypercapnic ventilatory response (delta VE/delta PaCO2) and central respiratory drive (delta P0.1/delta PaCO2) as well as the effects on hemodynamics, ventilation, and gas exchange in 10 male patients (mean age, 59 +/- 2 yr). The patients had a severe degree of chronic air-flow obstruction (FEV1, 1.07 +/- 0.08 L) and mild pulmonary hypertension (mean pulmonary artery pressure, 25 +/- 4 mm Hg). After hydralazine, the slope of delta VE/delta PaCO2 increased by 177% (p less than 0.005), and the slope of delta P0.1/delta PaCO2 increased by 145% (p less than 0.05). Resting ventilation increased from 14.8 +/- 1.0 to 17.1 +/- 1.4 L/min (p less than 0.02), primarily as a result of increased respiratory frequency. After hydralazine, PaO2 increased from 66 +/- 4 to 70 +/- 3 mm Hg (p less than 0.05) at rest and from 54 +/- 3 to 59 +/- 3 mm Hg (p less than 0.02) during exercise. PaCO2 decreased from 46 +/- 3 to 42 +/- 3 mm Hg (p less than 0.001) at rest and from 50 +/- 3 to 45 +/- 3 mm Hg (p less than 0.001) during exercise. No change was seen in the dead space to tidal volume ratio or the degree of venous admixture. Mean pulmonary artery pressure and total pulmonary resistance both at rest and during exercise were unchanged after hydralazine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Airway pressure release ventilation in severe acute respiratory failure

Airway pressure release ventilation (APRV), a new ventilatory support technique, was compared with conventional intermittent positive-pressure ventilation plus PEEP (CPPV) in 18 patients with severe acute respiratory failure. Patients were initially stabilized on CPPV and then switched to APRV. The APRV provided effective ventilatory support in 17 of 18 patients; APRV achieved similar levels of alveolar ventilation as CPPV (for APRV, mean PaCO2 = 45.0 +/- 6.2 mm Hg; vs for CPPV, mean PaCO2 = 43.3 +/- 5.7 mm Hg), with significantly lower mean maximum airway pressures (38.9 +/- 10.1 cm H2O vs 64.6 +/- 15.4 cm H2O; p = 0.0001) and mean VT (0.79 +/- 0.11 L vs 1.05 +/- 0.15 L; p = 0.0002). No significant differences in mean airway pressure, end-expiratory pressure, FIO2, ventilator rate, arterial blood gas levels, and hemodynamic function were noted between APRV and CPPV.     

Role of hypoxic drive in regulation of postapneic ventilation during sleep in patients with obstructive sleep apnea

To elucidate the role of chemoresponsiveness in determining postapneic ventilation in sleep-disordered periodic breathing, we measured ventilatory response associated with apnea-induced arterial oxygen desaturation during sleep and compared it with the awake hypoxic ventilatory response (HVR) in 12 male patients with obstructive sleep apnea (OSA). Awake HVR was measured at a slight hypocapnic level (end-tidal PCO2 = 37 +/- 1 mm Hg, mean +/- SEM), and separately at a PCO2 of 45 mm Hg. During non-REM sleep both the ventilatory rate (VE) and the average respiratory frequency (f) in the ventilatory phase between apneic episodes were inversely correlated with the nadir of arterial oxygen saturation (nSaO2) produced by the preceding apneic phase in all patients (VE versus nSaO2; r = -0.74 +/- 0.03, mean +/- SEM; f versus nSaO2, r = -0.56 +/- 0.04). The average tidal volume (VT) also was correlated with nSaO2 in 10 of the patients (r = -0.56 +/- 0.05). During REM sleep VE was correlated with nSaO2 in 11 patients (r = -0.75 +/- 0.03, p less than 0.02). The response of VE to nSaO2 (delta VE/delta nSaO2) varied widely among the patients (non-REM, 0.52 to 2.16; REM, 0.29 to 1.44 L/min/%) and was significantly lower during REM than non-REM sleep (p less than 0.01). The value of delta VE/delta nSaO2 during both non-REM and REM sleep was correlated with awake HVR at an end-tidal PCO2 of 45 mm Hg (non-REM, r = 0.83, p less than 0.02; REM, r = 0.76, p less than 0.05) but not with that at the hypocapnic level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory response and ventilatory muscle recruitment during arm elevation in normal subjects.

Despite the fact that the arms are used extensively in daily life and that some of the muscles of the shoulder girdle share both a respiratory and a positional function for the arms, surprisingly little is known about the respiratory response to unsupported upper extremity activity. To determine the respiratory consequences of simple arm elevation during tidal breathing, we measured minute ventilation (VE), tidal volume (VT), respiratory rate (f), heart rate (HR), oxygen uptake (VO2), and carbon dioxide production (VCO2) in 22 normal subjects seated with arms elevated in front of them to shoulder level (AE) for 2 min and down at the sides (AD) for the same time period. The sequence was randomized. Compared with AD, during AE there were significant increases in VO2 (336 +/- 18 vs 289 +/- 14 ml/min, p less than 0.001), VCO2 (315 +/- 23 vs 245 +/- 16 ml/min, p less than 0.001), HR (84 +/- 6 vs 73 +/- 4 beats/min, p less than 0.05), VE (11.5 +/- 0.9 vs 9.3 +/- 0.6 L/min, p less than 0.001), and VT (868 +/- 66 vs 721 +/- 48 ml, p less than 0.001). In 11 subjects, breath-by-breath metabolic and ventilatory parameters were studied with AD for 2 min, AE for 2 min, and with AD for 3 min while also recording gastric (Pg), pleural (Ppl), and transdiaphragmatic pressures (Pdi). With AE, there was a significant increase in Pg at end inspiration (PgI, 15.4 +/- 3.2 vs 11.9 +/- 2.7 cm H2O, p less than 0.01) and in Pdi (26.5 +/- 3.4 vs 21.4 +/- 2.4 cm H2O, p less than 0.01) with no change in Pg at end expiration (PgE) or in Ppl. The increases in VO2, VCO2, VE, and VT during arm elevation persisted for 2 min after arm lowering, whereas Pgi and Pdi abruptly dropped as the arms were lowered. We conclude that simple arm elevation during tidal breathing results in significant increases in metabolic and ventilatory requirements. These increased demands are associated with higher PgI and Pdi suggesting an increased diaphragmatic contribution to the generation of ventilatory pressures. The sudden drop in Pg with arm lowering indicate a change in ventilatory muscle and or torso recruitment independent of the metabolic drive and ventilatory needs. These findings may help explain the limitation that has been reported in some normal subjects and in many patients with lung disease during unsupported upper extremity activity.     

Active inspiratory impedance and neuromuscular respiratory output during halothane anaesthesia in humans

The aim of this study was to measure, in 11 patients with healthy lungs, active inspiratory impedance during anaesthesia. In addition, we recorded changes in inspiratory occlusion pressure at 100 ms (P0.1) and ventilatory pattern while awake and during anaesthesia with a mean inspiratory fraction (FI) of 0.017 halothane in O2. The total active inspiratory resistance and elastance values were 5.4 +/- 3.3 hPa.l.1.s and 29.9 +/- 6.2 hPa.l.1, respectively. P0.1 and the ratio between P0.1 and mean inspiratory flow (P0.1/(VT/TI)) increased 124% (p less than 0.001) and 68% (p less than 0.001), respectively, during anaesthesia. Respiratory frequency rose significantly from 12.2 +/- 1.5 (mean +/- SD) to 24.6 +/- 4.6 cycles.min-1, while tidal volume and inspiratory duty cycle lowered significantly from 0.599 +/- 0.195 l and 0.44 +/- 0.04 to 0.372 +/- 0.088 l (p less than 0.001) and 0.40 +/- 0.04 (p less than 0.05), respectively. Minute ventilation (VE) and VT/TI did not change significantly. During halothane anaesthesia with an FI:0.017, the increase in neuromuscular respiratory output appears to compensate for the increased mechanical load, thus resulting in maintenance of VE at levels similar to those of an awake state.     

Airways response of asthmatics after a 30 min exposure, at resting ventilation, to 0.25 ppm NO2 or 0.5 ppm SO2

We compared the effect of inhaled NO2 and SO2 on airway tone and airway responsiveness in 14 nonsmoking mild asthmatics (mean +/- SD age 34 +/- 14 yrs; mean +/- SD baseline forced expiratory volume in one second (FEV1), 86 +/- 17% pred). On 3 separate days, 30 min tidal breathing (average minute ventilation 10.6 l.min-1) of either filtered air, 0.25 ppm NO2, or 0.5 ppm SO2 was followed by an isocapnic hyperventilation test with 0.75 ppm SO2. To determine the provocative ventilation necessary to increase specific airway resistance (sRaw) by 100% (PV100sRaw) ventilation was increased in steps of 15 l.min-1, each step lasting 3 min. Resting ventilation of filtered air, NO2, or SO2 was followed by a slight but significant overall decrease of sRaw from 8.8 to 7.7 cmH20.s-1, with no differences between the study days. Mean +/- SEM PV100sRaw(SO2) was 46.5 +/- 5.1, 37.7 +/- 3.5 and 45.4 +/- 4.2 l.min-1 after tidal breathing of filtered air, NO2, and SO2, respectively. PV100sRaw(SO2) was significantly lower after NO2 as compared to filtered air or SO2 (p less than 0.01). There was a significant correlation (rs = 0.86) between the individual shift of PV100sRaw(SO2) after NO2 and the shift after SO2 as compared to filtered air. From these individual comparisons we suggest that in asthmatics short-term exposure to NO2 at rest enhances airway responsiveness to hyperventilation of SO2 without altering airway tone, whereas short-term exposure with low concentrations of SO2 does not.     

Ventilatory effects of doxapram in conscious human subjects

The ventilatory effects of a bolus intravenous dose of doxapram (0.37 to 0.47 mg/kg) were studied in ten healthy normal subjects. An immediate significant (p less than 0.001) increase in minute ventilation (VE) was due, in equal part, to significant increases in tidal volume (VT) and frequency (f). The inspiratory (TI) and expiratory time (TE) per breath decreased significantly. Mouth occlusion pressure increased significantly, in association with the increase in VT; there was no change in the ratio of VE to mouth occlusion pressure, indicating that respiratory mechanics did not alter. These results indicate that doxapram increases ventilation in conscious, normal man by an increase in inspiratory neuromuscular drive and a change in central breath timing. The ventilatory and mouth occlusion pressure responses to progressive isocapnic hypoxia and progressive hyperoxic hypercapnia were significantly altered by an intravenous infusion of doxapram (1 mg/min) only in the elevations (Y-intercepts) of the slopes of VE and mouth occlusion pressure; the regression coefficients did not change significantly. These results indicate that in conscious normal subjects, doxapram acts on both the peripheral and central respiratory receptors.     

Influence of respiratory behavior on ventilation,respiratory work and intrinsic PEEP during noninvasive nasal pressure support ventilation in normal subjects

BACKGROUND: In clinical practice, patients have different inspiratory behaviors during noninvasive pressure support ventilation (PSV): some breathe quietly, others actively help PSV by an additional effort, and others even resist the inspiratory pressure of PSV. OBJECTIVE: What is the influence of patient collaboration (inspiratory behavior) on the efficiency of PSV? METHODS: We ventilated 10 normal subjects with nasal PSV (inspiratory/expiratory: 10/0 and 15/5 cm H(2)O) and measured their flow and volume with a pneumotachograph and their esophageal and gastric pressures during three different respiratory voluntary behaviors: relaxed inspiration, active inspiratory work and resisted inspiration. RESULTS: When compared with relaxed inspiration with 10/0 cm H(2)O PSV: (1) an active inspiratory effort increased tidal volume (from 789 +/- 356 to 1,046 +/- 586 ml; p = 0.006), minute ventilation (from 10.40 +/- 4.45 to 15.77 +/- 7.69 liters/min; p < 0.001), transdiaphragmatic work per cycle (from 0.55 +/- 0.33 to 1.72 +/- 1.40 J/cycle; p = 0.002) and inspiratory work per cycle (from 0.14 +/- 0.20 to 1.26 +/- 1.01 J/cycle; p = 0.003); intrinsic positive end-expiratory pressure (PEEP(i)) increased from 1.23 +/- 1.02 to 3.17 +/- 2.30 cm H(2)O; p = 0.002); (2) a resisted inspiration decreased tidal volume (to 457 +/- 230 ml; p = 0.007), minute ventilation (to 6.93 +/- 3.04 liters/min; p = 0.028) along with a decrease in transdiaphragmatic work but no change in PEEP(i). Data obtained during a bilevel PSV of 15/5 cm H(2)O were similar to those obtained with the 10/0 cm H(2)O settings. CONCLUSIONS: Active inspiratory effort increases ventilation during PSV at the expense of an increased breathing work and PEEP(i). Resisted inspiration inversely decreases inspiratory work and ventilation with no air trapping. These differences between inspiratory behaviors could affect the expected beneficial effects of PSV in acutely ill patients.     

Effects of external diaphragm pacing on transdiaphragmatic pressure, ventilation and arterial blood gases in healthy volunteers

The effects of external diaphragm pacing (EDP) were studied in seven healthy volunteers. During EDP the movement of both left and right hemidiaphragms increased on average 1.28 and 1.30 cm respectively. The transdiaphragmatic pressure also increased from 8.63 +/- 1.576 cm H2O to 15.18 +/- 1.946 cm H2O (P less than 0.01). Inductive plethysmography showed that with EDP the mean inspiratory flow rate increased from 308 +/- 28.6 ml/sec. to 454 +/- 36.6 ml/sec. (P less than 0.01), but there was no change in respiratory rate, inspiratory time and the ratio of inspiratory time to respiratory cycle. Both tidal volume and minute volume of ventilation increased from 419 +/- 33.9 ml to 691 +/- 71.5 ml (P less than 0.01) and from 7.02 +/- 0.74 l/min. to 10.14 +/- 0.73 l/min. (P less than 0.01) respectively. Accompanied with the change of ventilation, the consumption of oxygen and the production of CO2 also increased from 258 +/- 14.9 ml/min. to 310 +/- 15.0 ml/min. (P less than 0.05) and from 228 +/- 11.4 ml/min. to 299 +/- 25.9 ml/min. (P less than 0.05) respectively. Consequently PaCO2 reduced from 5.24 +/- 0.22 kPa to 4.27 +/- 0.25 kPa (P less than 0.05), whereas PaO2 increased from 12.7 +/- 0.32 kPa to 14.5 +/- 0.42 kPa (P less than 0.01).     

Analysis of ventilatory parameters of nocturnal disturbed breathing in the elderly

To elucidate the effects of aging on ventilation in nocturnal disturbed breathing (NDB), we investigated 16 subjects aged 65 years or over with system developed by the authors using a respiratory inductive plethysmography connected to a personal computer. The subjects underwent 10 hours of continuous monitoring of lung volume and SaO2. Significant desaturation (SDS, greater than 4% drop in SaO2 from baseline value) and desaturation index [DI, sigma SDS(%) X duration (hr)] were calculated using the same program. The subjects with SDS below 50 were assigned to group A (n = 9, mean age = 79.7, male:female = 8:1) and the remaining subjects with SDS over 50 (n = 7, mean age = 74.7, male:female = 3:4) to group B. There was no significant difference in ventilatory parameters between group A and B. We then compared the male group (n = 11, mean age = 77.8) with the female group (n = 5, mean age = 76.8). The number of SDS in the female group (101.4 +/- 34.7) was significantly greater than that of the male group (33.4 +/- 8.3*, p less than 0.02), while minute ventilation of the female group (5.25 +/- 0.31 l/min) was significantly smaller than that of the male group (8.86 +/- 1.36* l/min, p less than 0.05). DI was found to significantly correlate with the SaO2 nadir and the number of apnea and SDS. There was no significant relationship between SDS and ventilatory parameters in this study. NDB among elderly female may be of more importance than has been reported.     

Effect of dynamic airway compression on breathing pattern and respiratory sensation in severe chronic obstructive pulmonary disease

Patients with severe COPD are frequently flow-limited during expiration at rest. When expiratory flow is at its maximum, application of negative pressure at the mouth should accentuate dynamic compression downstream from the flow-limiting segment (FLS) without substantially affecting flow or pressure upstream. The purpose of this study was to determine the ventilatory response to such intervention and to determine its effect on respiratory sensation. Such responses should reflect the effect of airway receptors downstream from the FLS. Nine patients with severe COPD (FEV1 +/- SE = 27 +/- 3% predicted) breathed into a closed-circuit apparatus that incorporated a rolling-seal spirometer. The spirometer was fitted with a linear actuator that caused mouth pressure to become negative in proportion to expiratory flow (expiratory assistance, EA). Ventilatory responses were measured during 4 min of EA (-9.7 cm H2O/L/s) and were compared with those during control periods (4 min each) before and after this (C1 and C2). Sense of breathing effort was assessed at 1-min intervals by asking the subject to point to a category scale of 1 to 5, with 1 being minimal effort and 5 indicating that breathing was very difficult. There were small but significant (p less than 0.05) decreases in TI (mean +/- SE, -0.2 +/- 0.05 s) and TE (-0.3 +/- 0.07 s), with increases in breathing frequency (+2.25 +/- 0.7) and ventilation (+1.5 +/- 0.6 L/min). No significant changes were observed in tidal volume or end-expiratory volume. The EA caused a highly significant (p less than 0.001) increase in the sense of breathing effort.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory constraints during exercise in patients with chronic heart failure

We examined the degree of ventilatory constraint in patients with a history of chronic heart failure (CHF; n = 11; mean +/- SE age, 62 +/- 4 years; cardiac index [CI], 2.0 +/- 0.1; and ejection fraction [EF], 24 +/- 2%) and in control subjects (CTLS; n = 8; age, 61 +/- 5 years; CI, 2.6 +/- 0.3) by plotting the tidal flow-volume responses to graded exercise in relationship to the maximal flow-volume envelope (MFVL). Inspiratory capacity (IC) maneuvers were performed to follow changes in end-expiratory lung volume (EELV) during exercise, and the degree of expiratory flow limitation was assessed as the percent of the tidal volume (VT) that met or exceeded the expiratory boundary of the MFVL. CHF patients had significantly (p < 0.05) reduced baseline pulmonary function (FVC, 76 +/- 4%; FEV(1), 78 +/- 4% predicted) relative to CTLS (FVC, 99 +/- 4%; FEV(1), 102 +/- 4% predicted). At peak exercise, oxygen consumption (VO(2)) and minute ventilation (V(E)) were lower in CHF patients than in CTLS (VO(2), 17 +/- 2 vs 32 +/- 2 mL/kg/min; VE, 56 +/- 4 vs 82 +/- 6 L/min, respectively), whereas VE/carbon dioxide output was higher (42 +/- 4 vs 29 +/- 5). In CTLS, EELV initially decreased with light exercise, but increased as VE and expiratory flow limitation increased. In contrast, the EELV in patients with CHF remained near residual volume (RV) throughout exercise, despite increasing flow limitation. At peak exercise, IC averaged 91 +/- 3% and 79 +/- 4% (p < 0.05) of the FVC in CHF patients and CTLS, respectively, and flow limitation was present over > 45% of the VT in CHF patients vs < 25% in CTLS (despite the higher VE in CTLS). The least fit and most symptomatic CHF patients demonstrated the lowest EELV, the greatest degree of flow limitation, and a limited response to increased inspired carbon dioxide during exercise, all consistent with VE constraint. We conclude that patients with CHF commonly breathe near RV during exertion and experience expiratory flow limitation. This results in VE constraint and may contribute to exertional intolerance.