Constant VT Research Articles

What CPAP to use in the delivery room? Bench comparison of two methods to provide continuous positive airways pressure in neonates

BackgroundContinuous positive airway pressure (CPAP) is a recommended first-line therapy for infants with respiratory distress at birth. Resuscitation devices incorporating CPAP delivery can have significantly different imposed resistances affecting airway...

Tidal volume selection in volume-controlled ventilation guided by driving pressure versus actual body weight in healthy anesthetized and mechanically ventilated dogs: A randomized crossover trial

ObjectiveTo compare static compliance of the respiratory system (CstRS) and the ratio of partial pressure of end-tidal to arterial carbon dioxide (Pe′CO2/PaCO2), in healthy dogs using two approaches for tidal volume (VT) selection during volume-controlled ventilation: body mass based and driving pressure (ΔPaw) guided. Study designRandomized, nonblinded, crossover, clinical trial. AnimalsA total of 19 client-owned dogs anesthetized for castration and ovariohysterectomy. MethodsAfter a stable 10 minute baseline, each dog was mechanically ventilated with a VT selection strategy, randomized to a constant VT of 15 mL kg–1 of actual body mass (VTBW) or ΔPaw-guided VT (VTΔP) of 7–8 cmH2O. Both strategies used an inspiratory time of 1 second, 20% end-inspiratory pause, 4 cmH2O positive end-expiratory pressure and fraction of inspired oxygen of 0.4. Respiratory frequency was adjusted to maintain Pe′CO2 between 35 and 40 mmHg. Respiratory mechanics, arterial blood gases and Pe′CO2/PaCO2 were assessed. Continuous variables are presented as mean ± SD or median (interquartile range; quartiles 1–3), depending on distribution, and compared with Wilcoxon signed-rank tests. ResultsThe VT was significantly higher in dogs ventilated with VTΔP than with VTBW strategy (17.20 ± 4.04 versus 15.03 ± 0.60 mL kg–1, p = 0.036). CstRS was significantly higher with VTΔP than with VTBW strategy [2.47 (1.86–2.86) versus 2.25 (1.79–2.58) mL cmH2O−1 kg–1, p = 0.011]. There were no differences in Pe′CO2/PaCO2 between VTΔP and VTBW strategies (0.94 ± 0.06 versus 0.92 ± 0.06, p = 0.094). No discernible difference in ΔPaw was noted between the strategies. Conclusions and clinical relevanceWhile no apparent difference was observed in the Pe′CO2/PaCO2 between the VT selection strategies employed, CstRS significantly increased during the VTΔP approach. A future trial should explore if VTΔP improves perioperative gas exchange and prevents lung damage.

Hyperventilation in Patients with Postural Orthostatic Tachycardia Syndrome (POTS): Effects of Tidal Volume versus Hypocapnia on Heart Rate

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a chronic form of orthostatic intolerance that significantly impacts the quality of life and day-to-day functioning of patients. POTS has an estimated prevalence of about 1%, predominantly affecting females of child-bearing age. POTS is characterized by an upright increase in heart rate (HR) of ≥30 bpm, without a drop in blood pressure. POTS is associated with chronic (≥ 3 months) upright symptoms including light-headedness, blurred vision, and cognitive dysfunction. A large proportion of POTS patients also experience hyperventilation when upright. Hyperventilation reduces arterial carbon dioxide (CO2; hypocapnia) and exacerbates tachycardia in POTS. Whether the HR response is due to increased tidal volume (VT) per se or the resulting hypocapnia is unclear. Investigating the independent effects of increased VT versus hypocapnia on HR might identify possible therapeutic targets to reduce HR in patients with POTS. Objective: We aimed to characterize the separate effects of hypocapnia and VT on HR in POTS patients. Hypothesis: We hypothesize that hypocapnia and VT will independently increase HR, with hypocapnia causing the greatest increase in HR in patients with POTS. Methods: Twenty female POTS patients (32±10 years) completed supine normocapnic and hypocapnic breathing tests. To assess the effects of hypocapnia on HR, we compared hypocapnic-hyperventilation versus normocapnic-hyperventilation with constant VT. To assess the effects of VT on HR, we compared increased VT breathing versus normal breathing with constant end-tidal CO2 (ETCO2). Breath-by-breath respiratory (VT, ETCO2) and beat-to-beat hemodynamic parameters (stroke volume [SV], HR) were continuously measured. Data were analyzed with paired t-tests, and are reported as mean ± SD. Results: ETCO2 was lower ( p<0.001) with similar VT during hypocapnia compared to normocapnia. Hypocapnia reduced SV (63.3±11.8 mL vs. 72.4±12.3 mL; p<0.001), and increased HR (99±13 bpm vs. 81±9 bpm; p<0.001). Compared to normal breathing, increased VT ( p<0.001) with constant ETCO2 led to a smaller reduction in SV (72.4±12.3 mL vs. 76.0±14.3 mL; p=0.04), and increase in HR (81±9 bpm vs. 75±9 bpm; p<0.001). Conclusion: Our results suggest that hypocapnia and increased VT independently reduce SV and increase HR in POTS patients. The increase in HR was greater during hypocapnia (+18 bpm) compared to increased VT (+6 bpm). Reducing hypocapnia presents an attractive therapeutic target. Disclosures: This work was supported by Standing up to POTS. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Experimental and simulated etched track profiles for two relativistic ions treated under different etching conditions: How to shape different track envelopes

PADC polymer sheets of thickness 650 μm were exposed to normal incident high energy ions of 7 GeV Si and 17.48 GeV Ni with particle density ≈ 103 particles/cm2. Chemical etching was carried out under soft and strong etching conditions, and parameters of track diameter and cone length variation with depths were measured and recorded at successive times during the etching process, including snapshots of the etched track profiles. A computer program using a sophisticated chemical etching model including a variation of the bulk etching rate of the detector material was used. This program uses experimental data of a variable bulk etch rate with depth (Vb (z)) and an average longitudinal (Vt) etching rate, for each etching condition and ion. A good agreement is obtained between simulation and experiment in all cases, which validates the choice of the model used and the constant Vt approximation. It is shown that the same latent track due to a given ion gives different three-dimensional shapes depending on the chemical etching conditions used. The production of etched tracks with funnel shapes is one of the originalities of this work. The simulation tool developed allows for exploring the production of microcavities with specific shapes using polymer sheets exposed to high-energy ions.

Constant Vt Ventilation and Surfactant Dysfunction: An Overlooked Cause of Ventilator-induced Lung Injury.

Ventilator-induced lung injury (VILI) is currently ascribed to volutrauma and/or atelectrauma, but the effect of constant Vt ventilation (CVtV) has received little attention. This Perspective summarizes the literature documenting that CVtV causes VILI and reviews the mechanisms by which it occurs. Surfactant is continuously inactivated, depleted, displaced, or desorbed as a function of the duration of ventilation, the Vt, the level of positive end-expiratory pressure (PEEP), and possibly the respiratory rate. Accordingly, surfactant must be continuously replenished, and secretion primarily depends on intermittent delivery of large ventilatory excursions. The surfactant abnormalities resulting from CVtV result in atelectasis and VILI. Although surfactant secretion is reduced by the absence of intermittent deep breaths, continuous administration of large Vts depletes surfactant and impairs subsequent secretion. Low or normal lung volumes result in desorption of surfactant. PEEP can be protective by reducing surface film collapse and subsequent film rupture on reexpansion, and/or by reducing surfactant displacement into the airways, but PEEP can also downregulate surfactant release. The effect of CVtV on surfactant is complex. If attention is not paid to facilitating surfactant secretion and limiting its inactivation, depletion, desorption, or displacement, surface tension will increase and atelectasis and VILI will occur.

Gradually Increasing Tidal Volume May Mitigate Experimental Lung Injury in Rats

This study hypothesized that, in experimental mild acute respiratory distress syndrome, lung damage caused by high tidal volume (VT) could be attenuated if VT increased slowly enough to progressively reduce mechanical heterogeneity and to allow the epithelial and endothelial cells, as well as the extracellular matrix of the lung to adapt. For this purpose, different strategies of approaching maximal VT were tested. Sixty-four Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, animals were randomly assigned to receive mechanical ventilation with VT = 6 ml/kg for 2 h (control); VT = 6 ml/kg during hour 1 followed by an abrupt increase to VT = 22 ml/kg during hour 2 (no adaptation time); VT = 6 ml/kg during the first 30 min followed by a gradual VT increase up to 22 ml/kg for 30 min, then constant VT = 22 ml/kg during hour 2 (shorter adaptation time); and a more gradual VT increase, from 6 to 22 ml/kg during hour 1 followed by VT = 22 ml/kg during hour 2 (longer adaptation time). All animals were ventilated with positive end-expiratory pressure of 3 cm H2O. Nonventilated animals were used for molecular biology analysis. At 2 h, diffuse alveolar damage score and heterogeneity index were greater in the longer adaptation time group than in the control and shorter adaptation time animals. Gene expression of interleukin-6 favored the shorter (median [interquartile range], 12.4 [9.1-17.8]) adaptation time compared with longer (76.7 [20.8 to 95.4]; P = 0.02) and no adaptation (65.5 [18.1 to 129.4]) time (P = 0.02) strategies. Amphiregulin, metalloproteinase-9, club cell secretory protein-16, and syndecan showed similar behavior. In experimental mild acute respiratory distress syndrome, lung damage in the shorter adaptation time group compared with the no adaptation time group was attenuated in a time-dependent fashion by preemptive adaptation of the alveolar epithelial cells and extracellular matrix. Extending the adaptation period increased cumulative power and did not prevent lung damage, because it may have exposed animals to injurious strain earlier and for a longer time, thereby negating any adaptive benefit.

Additive effect of simultaneously varying respiratory frequency and tidal volume on respiratory sinus arrhythmia.

Our aims were to assess, in healthy young females and males, the effects of the linear joint variation of respiratory frequency (RF) and tidal volume (VT) on the logarithmic transformation of high-frequency power of RR intervals (lnHF). ECG and VT were recorded from 18 females and 20 males during three visually guided 30-s breathing maneuvers: linearly increasing RF (RFLI) at constant VT; linearly increasing VT (VTLI) followed by decreasing VT (VTLD) at fixed RF, and RFLI and VTLI-VTLD combined. VT of females was 20% smaller. Instantaneous RF and lnHF were computed from the time-frequency distributions of respiratory series and RR intervals. LnHF-RF and lnHF-VT relations were similar between genders. LnHF and RR intervals control-maneuver differences during combined maneuver were approximately equal to the sum of those of the independent maneuvers. LnHF-RFLI relation showed strong negative correlations in separated and combined conditions, with steeper slope in the latter (p < 0.001). LnHF-VTLI and lnHF-VTLD relations presented, in the independent maneuvers, three combinations of slopes of different sign, all with hysteresis, and in the combined maneuver, strong correlations with negative slope for VTLI and positive slope for VTLD, steeper (p < 0.001) and with greater hysteresis (p < 0.001) than the independent ones. LnHF responses to our fast, non-fatiguing and non-steady-state breathing maneuvers are: similar between genders; consistent attenuation due to RFLI, whether applied alone or combined; ambiguous and with hysteresis to independent VTLI-VTLD variations; systematic greater attenuation during RFLI combined with VTLI-VTLD, equal to the sum of the independent effects, indicating that there is no interference between them.

Does pressure-controlled ventilation-volume guaranteed differ from pressure-controlled ventilation in anesthetized patients

Background General anesthesia causes depression of both respiratory centers and respiratory muscles. Hence, patients under general anesthesia require ventilatory support to maintain arterial oxygenation and eliminate carbon dioxide. Mechanical ventilation can improve patients outcome. The purpose of this study was to determine whether pressure-controlled ventilation-volume guaranteed (PCV-VG) provide better oxygenation than pressure-controlled ventilation (PCV) in anesthetized patients. Patients and methods A total of 30 patients scheduled for abdominal cancer surgery under general anesthesia were enrolled in the study. Mechanical ventilation was started with PCV for 60 min then PCV-VG was applied to all patients with the same parameters, targeting the obtained tidal volume (Vt). Arterial blood pressures, heart rate, ETCO 2 , SpO 2 , pH, PaCO 2 , and PaO 2 were measured after 60 min of intubation during PCV and after 60 min of initiation of PCV-VG. Vt, mean airway pressure, and peak airway pressure (during PCV-VG) were recorded. Oxygenation index calculation was performed at the preset times. Results All parameters were comparable with no significant difference between both modes of ventilation in anesthetized patients ( P ≥ 0.05). Conclusion While maintaining constant Vt and I/E ratio, there were no significant differences in respiratory and ventilatory parameters, and also the oxygenation index was comparable between both PCV and PCV-VG modes of ventilation.

Compartmental chest wall volume changes during volitional hyperpnoea with constant tidal volume in healthy individuals

Prolonged high-intensity ventilation is associated with the development of rapid shallow breathing with decreased end-inspiratory volumes of all chest wall compartments. During respiratory muscle endurance training using normocapnic hyperpnoea, tidal volume (VT) is normally kept constant. The aim of this study was to investigate possible changes in muscle recruitment during constant-VT hyperpnoea, to assess potential mechanisms related to rapid shallow breathing. Ten healthy subjects performed 1h of normocapnic hyperpnoea at 70% of maximal voluntary ventilation. Chest wall volume changes were assessed by optoelectronic plethysmography. End-inspiratory (1.08±0.18 versus 0.96±0.27 l, p=0.017) and end-expiratory volumes (−0.13±0.15 versus −0.31±0.19 l, p=0.007) of the pulmonary ribcage decreased significantly and lung function and respiratory muscle strength were reduced (all p<0.05). Since with forced, constant VT only the inspiratory rib cage muscles were unable to sustain end-inspiratory volume of their compartment, inspiratory rib cage muscles are the most likely candidate responsible for the development of rapid shallow breathing.

Effects of assisted and variable mechanical ventilation on cardiorespiratory interactions in anesthetized pigs

The physiological importance of respiratory sinus arrhythmia (RSA) and cardioventilatory coupling (CVC) has not yet been fully elucidated, but these phenomena might contribute to improve ventilation/perfusion matching, with beneficial effects on gas exchange. Furthermore, decreased RSA amplitude has been suggested as an indicator of impaired autonomic control and poor clinical outcome, also during positive-pressure mechanical ventilation (MV). However, it is currently unknown how different modes of MV, including variable tidal volumes (VT), affect RSA and CVC during anesthesia. We compared the effects of pressure controlled (PCV) versus pressure assisted (PSV) ventilation, and of random variable versus constant VT, on RSA and CVC in eight anesthetized pigs. At comparable depth of anesthesia, global hemodynamics, and ventilation, RSA amplitude increased from 20 ms in PCV to 50 ms in PSV (p < 0.05). CVC was detected (using proportional Shannon entropy of the interval between each inspiration onset and the previous R-peak in ECG) in two animals in PCV and seven animals in PSV. Variable VT did not significantly influence these phenomena. Furthermore, heart period and systolic arterial pressure oscillations were in phase during PCV but in counter-phase during PSV. At the same depth of anesthesia in pigs, PSV increases RSA amplitude and CVC compared to PCV. Our data suggest that the central respiratory drive, but not the baroreflex or the mechano-electric feedback in the heart, is the main mechanism behind the RSA increase. Hence, differences in RSA and CVC between mechanically ventilated patients might reflect the difference in ventilation mode rather than autonomic impairment. Also, since gas exchange did not increase from PCV to PSV, it is questionable whether RSA has any significance in improving ventilation/perfusion matching during MV.

Pressure-controlled ventilation and intrabronchial pressure during one-lung ventilation

BackgroundPressure-controlled ventilation (PCV) has been suggested to reduce peak airway pressure (Ppeak) and intrapulmonary shunt during one-lung ventilation (OLV) when compared with volume-controlled ventilation (VCV). At the same tidal volume (VT), the apparent difference in Ppeak is mainly related to the presence of a double-lumen tracheal tube. We tested the hypothesis that the decrease in Ppeak observed in the breathing circuit is not necessarily associated with a decrease in the bronchus of the dependent lung. MethodsThis observational study included 15 consecutive subjects who were ventilated with VCV followed by PCV at constant VT. Airway pressure was measured simultaneously in the breathing circuit and main bronchus of the dependent lung after 20 min of ventilation. ResultsPCV induced a significant decrease in Ppeak [mean (sd)] measured in the breathing circuit [36 (4) to 26 (3) cm H20, P<0.0001] and in the bronchus [23 (4) to 22 (3) cm H2O, P=0.01]. However, the interaction (ventilatory mode × site of measurement) revealed that the decrease in Ppeak was significantly higher in the circuit (P<0.0001). Although the mean percentage decrease in Ppeak was significant at both sites, the decrease was significantly lower in the bronchus [5 (6)% vs 29 (3)%, P<0.0001]. ConclusionsDuring PCV for OLV, the decrease in Ppeak is observed mainly in the respiratory circuit and is probably not clinically relevant in the bronchus of the dependent lung. This challenges the common clinical perception that PCV offers an advantage over VCV during OLV by reducing bronchial Ppeak.

Manual ventilation devices in neonatal resuscitation: Tidal volume and positive pressure-provision

Background Excessive peak inspiratory pressures (PIP) and high tidal volumes (Vt) during manual ventilation can be detrimental to the neonatal lung. We compared the influence of different manual ventilation devices and individual professional experience on the extent of applied Vt and PIP in simulated neonatal resuscitation. Material and methods One hundred and twenty medical professionals were studied. An intubated mannequin (equivalent to 1.0 kg neonate) was ventilated using two different devices: a self-inflating bag and a T-piece resuscitator. Target value was a PIP of 20 cm H 2O. Applied PIP and the resulting Vt were recorded continuously using a respiratory function monitor (CO 2SMO +, Novametrix, USA). Results Vt and PIP provision was significantly higher in SI-bags, compared to T-piece devices: median (interquartile range) PIP 25.6 (18.2) cm H 2O vs 19.7 (3.2) cm H 2O ( p < 0.0005), and Vt 5.1(3.2) ml vs Vt 3.6 (0.8) ml ( p < 0.0005) respectively. The intersubject variability of Vt and PIP provision was distinctly higher in SI-bags, compared to T-piece devices. Professional experience had no significant impact on the level and the variability of Vt or PIP provided. Conclusion Use of T-piece devices guarantees reliable and constant Vt and PIP provision, irrespective of individual, operator dependent variables. Methods to measure and to avoid excessive tidal volumes in neonatal resuscitation need to be developed.

Design of a new variable-ventilation method optimized for lung recruitment in mice

Variable ventilation (VV), characterized by breath-to-breath variation of tidal volume (Vt) and breathing rate (f), has been shown to improve lung mechanics and blood oxygenation during acute lung injury in many species compared with conventional ventilation (CV), characterized by constant Vt and f. During CV as well as VV, the lungs of mice tend to collapse over time; therefore, the goal of this study was to develop a new VV mode (VV(N)) with an optimized distribution of Vt to maximize recruitment. Groups of normal and HCl-injured mice were subjected to 1 h of CV, original VV (VV(O)), CV with periodic large breaths (CV(LB)), and VV(N), and the effects of ventilation modes on respiratory mechanics, airway pressure, blood oxygenation, and IL-1beta were assessed. During CV and VV(O), normal and injured mice showed regional lung collapse with increased airway pressures and poor oxygenation. CV(LB) and VV(N) resulted in a stable dynamic equilibrium with significantly improved respiratory mechanics and oxygenation. Nevertheless, VV(N) provided a consistently better physiological response. In injured mice, VV(O) and VV(N), but not CV(LB), were able to reduce the IL-1beta-related inflammatory response compared with CV. In conclusion, our results suggest that application of higher Vt values than the single Vt currently used in clinical situations helps stabilize lung function. In addition, variable stretch patterns delivered to the lung by VV can reduce the progression of lung injury due to ventilation in injured mice.

End-expiratory and tidal volumes measured in conscious mice using single projection x-ray images

The evaluation of airway resistance (R(aw)) in conscious mice requires both end-expiratory (V(e)) and tidal volumes (V(t)) (Lai-Fook SJ and Lai YL. J Appl Physiol 98: 2204-2218, 2005). In anesthetized BALB/c mice we measured lung area (A(L)) from ventral-to-dorsal x-ray images taken at FRC (V(e)) and after air inflation with 0.25 and 0.50 ml (DeltaV(L)). Total lung volume (V(L)) described by equation: V(L) = DeltaV(L) + V(FRC) = KA(L)(1.5) assumed uniform (isotropic) inflation. Total V(FRC) averaged 0.55 ml, consisting of 0.10 ml tissue, 0.21 ml blood and 0.24 ml air. K averaged 1.84. In conscious mice in a sealed box, we measured the peak-to-peak box pressure excursions (DeltaP(b)) and x-rays during several cycles. K was used to convert measured A(L)(1.5) to V(L) values. We calculated V(e) and V(t) from the plot of V(L) vs. cos(alpha - phi). Phase angle alpha was the minimum point of the P(b) cycle to the x-ray exposure. Phase difference between the P(b) and V(L) cycles (phi) was measured from DeltaP(b) values using both room- and body-temperature humidified box air. A similar analysis was used after aerosol exposures to bronchoconstrictor methacholine (Mch), except that phi depended also on increased R(aw). In conscious mice, V(e) (0.24 ml) doubled after Mch (50-125 mg/ml) aerosol exposure with constant V(t), frequency (f), DeltaP(b), and R(aw). In anesthetized mice, in addition to an increased V(e), repeated 100 mg/ml Mch exposures increased both DeltaP(b) and R(aw) and decreased f to apnea in 10 min. Thus conscious mice adapted to Mch by limiting R(aw), while anesthesia resulted in airway closure followed by diaphragm fatigue and failure.

Effects of tidal volume and respiratory frequency on lung lymph flow

Ventilation (V) increases lung lymph flow (Ql), but the separate effects of tidal volume (Vt) and frequency (f) and the role of V-induced changes in edema formation are poorly understood. An isolated, in situ sheep lung preparation was used to examine these effects. In eight sheep with f = 10 min(-1), results obtained during 30-min periods with Vt = 5 or 20 ml/kg were compared with values obtained during bracketed 30-min control periods (Vt = 12.5 ml/kg). Eight other sheep with constant Vt (12.5 ml/kg) were studied at f = 5 or 20 min(-1) and compared with f = 10 min(-1). Three additional groups of six sheep were perfused for 100 min with control V (10 ml/kg, 10 min(-1)). Vt was then kept constant or changed to 20 or 3 ml/kg during a second 100-min period. Increases in Vt or f increased Ql and vice versa, without corresponding effects on the rate of edema formation. For the same change in V, changing Vt had a greater effect on Ql than changing f. The change in Ql caused by an increase in Vt was significantly greater after the accumulation of interstitial edema. The change in Ql caused by a sustained increase in Vt was transient and did not correlate with the rate of edema formation, suggesting that V altered Ql through direct mechanical effects on edema-filled compartments and lymphatic vessels rather than through V-induced changes in fluid filtration.

Classification of Voronoi and Delone tiles of quasicrystals: III. Decagonal acceptance window of any size

This paper is the last of a series of three articles presenting a classification of Vornoi and Delone tilings determined by point sets ?(?) ('quasicrystals'), built by the standard projection of the root lattice of type A4 to a two-dimensional plane spanned by the roots of the Coxeter group H2 (dihedral group of order 10). The acceptance window ? for ?(?) in the present paper is a regular decagon of any radius 0 < r < ?. There are 14 distinct VT sets of Voronoi tiles and 6 sets DT of Delone tiles, up to a uniform scaling by the factor and . The number of Voronoi tiles in different quasicrystal tilings varies between 3 and 12. Similarly, the number of Delone tiles is varying between 4 and 6. There are 7 VT sets of the 'generic' type and 7 of the 'singular' type. The latter occur for seven precise values of the radius of the acceptance window. Quasicrystals with acceptance windows with radii in between these values have constant VT sets, only the relative densities and arrangement of the tiles in the tilings change. Similarly, we distinguish singular and generic sets DT of Delone tiles.

Variable ventilation induces endogenous surfactant release in normal guinea pigs.

Variable or noisy ventilation, which includes random breath-to-breath variations in tidal volume (Vt) and frequency, has been shown to consistently improve blood oxygenation during mechanical ventilation in various models of acute lung injury. To further understand the effects of variable ventilation on lung physiology and biology, we mechanically ventilated 11 normal guinea pigs for 3 h using constant-Vt ventilation (n = 6) or variable ventilation (n = 5). After 3 h of ventilation, each animal underwent whole lung lavage for determination of alveolar surfactant content and composition, while protein content was assayed as a possible marker of injury. Another group of animals underwent whole lung lavage in the absence of mechanical ventilation to serve as an unventilated control group (n = 5). Although lung mechanics did not vary significantly between groups, we found that variable ventilation improved oxygenation, increased surfactant levels nearly twofold, and attenuated alveolar protein content compared with animals ventilated with constant Vt. These data demonstrate that random variations in Vt promote endogenous release of biochemically intact surfactant, which improves alveolar stability, apparently reducing lung injury.

Direct effect of Pa(CO2) on respiratory sinus arrhythmia in conscious humans.

Respiratory sinus arrhythmia (RSA) may improve the efficiency of pulmonary gas exchange by matching the pulmonary blood flow to lung volume during each respiratory cycle. If so, an increased demand for pulmonary gas exchange may enhance RSA magnitude. We therefore tested the hypothesis that CO2 directly affects RSA in conscious humans even when changes in tidal volume (V(T)) and breathing frequency (F(B)), which indirectly affect RSA, are prevented. In seven healthy subjects, we adjusted end-tidal PCO2 (PET(CO2)) to 30, 40, or 50 mmHg in random order at constant V(T) and F(B). The mean amplitude of the high-frequency component of R-R interval variation was used as a quantitative assessment of RSA magnitude. RSA magnitude increased progressively with PET(CO2) (P < 0.001). Mean R-R interval did not differ at PET(CO2) of 40 and 50 mmHg but was less at 30 mmHg (P < 0.05). Because V(T) and F(B) were constant, these results support our hypothesis that increased CO2 directly increases RSA magnitude, probably via a direct effect on medullary mechanisms generating RSA.

Mathematical assessment of qualitative diagnostic calibration for respiratory inductive plethysmography.

We present a critical assessment of qualitative diagnostic calibration (QDC), which claims to provide a relative calibration of respiratory inductive plethysmography during natural breathing (Sackner MA, Watson H, Belsito AS, Feinerman D, Suarez M, Gonzalez G, Bizousky F, and Krieger B. J Appl Physiol 66: 410-420, 1989). QDC computes the calibration factor (K) by considering breaths of constant tidal volume (VT) and provides a criterion to select breaths when VT is unknown. We applied QDC on uncalibrated data constructed from simulated sets of thoracic and abdominal volumes, with a predefined K. As expected, QDC yields a correct K when applied to breaths at constant VT. In breathing at quasi-constant VT, the criterion for breath selection is shown to bias the results toward K = 1. For spontaneous breathing, the calculated K deviates from its predefined value and depends heavily on the selection criterion. We conclude that QDC will only provide a correct calibration factor when applied to an entire set of breaths with constant or quasi-constant VT. More generally, physiological conclusions based on QDC should be critically evaluated on a case-by-case basis.

Flow and volume dependence of respiratory mechanics in anesthetized children.

With the use of constant flow, end-inspiratory airway occlusion, respiratory system resistance (Rrs) can be partitioned into a flow resistive component (Rint) and an additional component (deltaR), reflecting viscoelasticity and time constant inequality. Similarly, respiratory system elastance (Edyn) can be partitioned into static elastance (Est) and elastance due to viscoelasticity and time constant inequality (deltaE). We measured Rrs and Edyn and their subdivisions (Rint and deltaR, Est and deltaE, respectively) and studied their flow and volume dependence in eight otherwise healthy children (median age 3.6 y; range 1.9-5.2 y) undergoing general anesthesia for oral rehabilitation. With a constant inspiratory flow (VI) of approximately 15 mL/s/kg and tidal volume of 12 mL/kg, the mean values of Rrs, Rint, and deltaR were: 0.20, 0.11, and 0.10 cmH2O/mL/s.kg. Under the same conditions, the mean Est and deltaE were: 1.04 and 0.12 cmH2O/mL/kg. With increasing VI and under constant VT, deltaR decreased (p < 0.001) progressively. Rint also decreased paradoxically (p < 0.001). Hence, Rrs decreased (p < 0.001) with increasing VI. Est decreased (p < 0.001) with increasing VI, whereas delta E increased (p < 0.005). With increasing VT and under constant VI, Rint decreased (p < 0.001) and deltaR tended to increase (p = 0.058); Rrs did not change. With increasing VT under constant VI, both Est and deltaE decreased (p < 0.001 and p = 0.001, respectively). Thus, in contrast to the findings in adults, Rint and Est decreased in children with increasing flow and under constant tidal volume, probably reflecting decreased functional residual capacity in anesthetized children, compared with adults. The flow and volume dependence of deltaR and deltaE were similar to those in adults, whereas Rrs did not necessarily follow the direction of changes of deltaR.