Pulmonary rapidly adapting receptors reflexly increase airway secretion in dogs

We attempted to determine whether stimulation of pulmonary rapidly adapting receptors (RARs) increase tracheal submucosal gland secretion in anesthetized open-chest dogs. Electroneurographic studies of pulmonary afferents established that RARs but not lung C-fibers were stimulated by intermittent lung collapse during deflation, collapse being produced by removing positive end-expiratory pressure (PEEP, 4 cmH2O) or by applying negative end-expiratory pressure (NEEP, -4 cmH2O). We measured tracheal secretion by the "hillocks" method. Removing PEEP or applying NEEP for 1 min increased secretion from a base line of 6.0 +/- 1.1 to 11.8 +/- 1.7 and 22.0 +/- 2.8 hillocks.cm-2.min-1, respectively (P less than 0.005). After PEEP was restored, dynamic lung compliance (Cdyn) was 37% below control, and secretion remained elevated (P less than 0.05). A decrease in Cdyn stimulates RARs but not other pulmonary afferents. Hyperinflation, which restored Cdyn and RAR activity to control, returned secretion rate to base line. Secretory responses to lung collapse were abolished by vagal cooling (6 degrees C), by pulmonary vagal section, or by atropine. We conclude that RAR stimulation reflexly increases airway secretion. We cannot exclude the possibility that reduced input from slowly adapting stretch receptors contributed to the secretory response.     

哇巴因刺激肺慢适应感受器

钠钾泵抑制剂——哇巴因能引起气道内慢适应感受器异相发放,表现为冲动在正常时的吸气相发放,呼气相终止转变为在呼气相发放,吸气相终止。我们推测异相发放由过度兴奋所致,如果假设正确,那么降低气道压力从而减少对感受器刺激,将能防止异相发放。本工作在麻醉、开胸、机械通气（在呼气末附加3cm水柱的正压）的家兔中记录颈迷走神经中慢适应感受器的单位放电,向感受野注射微量哇巴因（1μmol／L,20μ1）,可观察到感受器活动发生变化。感受器放电经历紧张性发放、异相发放、以及不规则发放三个时期,随后放电终止,进入静息状态。在紧张期,感受器呈持续发放,冲动频率随肺部通气变化的波动幅度明显减小。在异相发放期,感受器活动出现突然发放（呼气相）与终止（吸气相）,其冲动快速转换于高频发放和静止之间。此时,若撤除呼气末正压而减少气道内压力,感受器活动恢复正常,即冲动频率于气管压峰值时为最高,在呼气相减少或终止。在不规则期,感受器通常处于静止状态,时而出现突发高频冲动,且与呼吸周期无关。可以设想：在吸气相,感受器受到牵拉,引起钠、钙等阳离子内流,产生感受器电位。正常时,由于激活钠泵,将钠离子泵出细胞,使感受器电位回复。当钠泵受到抑制后,钠外流受阻,感受器电位加大。在异相发放期,肺充气时牵拉感受器,进一步增加感受器电位,当它超越了产生动作电位的活动范围后,则感受器因过度去极化而失去兴奋性。     

Airway mechanoreceptor deactivation.

Airway sensors play an important role in control of breathing. Recently, it was found that pulmonary slowly adapting stretch receptors (SARs) cease after a brief excitation following sodium pump blockade by ouabain. This deactivation can be explained by overexcitation. If this is true, mechanical stimulation of the SARs should also lead to a deactivation. In this study, we recorded unit activity of the SARs in anesthetized, open-chest, and mechanically ventilated rabbits and examined their responses to lung inflation at different constant pressures. Forty-seven of 137 units had a clear deactivation during the lung inflation. The deactivation threshold varied from unit to unit. For a given unit, the higher the inflation pressure, the sooner the deactivation occurs. For example, the SARs deactivated at 3.0 +/- 0.3 and 4.8 +/- 0.4 s when the lungs were inflated to constant pressures of 30 and 20 cmH(2)O, respectively (n = 25, P < 0.0001). The units usually ceased after a brief intense discharge. In some units, their activity shifted to a lower level, indicating a pacemaker switching. Our results support the notion that SARs deactivate due to overexcitation.     

Effects of potassium channel blockers on hyperinflation-induced rapidly adapting pulmonary stretch receptor stimulation in the rabbit.

The effects of K+ channel blockers, such as 4-aminoprydine (4-AP) and tetraethylammonium (TEA), on the excitatory responses of rapidly adapting pulmonary stretch receptor (RAR) activity to hyperinflation (inflation volume=3 tidal volumes) were investigated in anesthetized, artificially ventilated rabbits after vagus nerve section. The changes in the RAR adaptation index (AI) produced by constant-pressure (approximately 30 cmH2O, 29.7+/-0.2 cmH2O) inflation of the lungs were also examined before and after pretreatment with 4-AP and TEA. The administration of 4-AP (0.7 and 2.0 mg/kg) potentiated hyperinflation-induced RAR stimulation in a dose-dependent manner. During hyperinflation after 2.0 mg/kg 4-AP administration the discharge of RARs showed a relatively regular firing pattern in both inflation and deflation phases. The RAR AI values during constant-pressure inflation of the lungs were significantly reduced by 4-AP treatment (2.0 mg/kg). TEA treatment (2.0 and 7.0 mg/kg) did not significantly alter either the excitatory response of RAR activity to hyperinflation or the RAR AI values seen during constant-pressure inflation of the lungs. These results suggest that during hyperinflation in in vivo experiments on rabbits, RARs may be maintained at a lower activity by opening the 4-AP-sensitive K+ channels on the receptor endings, which can determine accommodation of the receptor discharge.     

Effect of PEEP on discharge of pulmonary C-fibers in dogs

Although positive end-expiratory pressure (PEEP) is believed to depress cardiac output and arterial pressure by compressing the vena cava and the heart, it is unclear whether PEEP also depresses these variables by a reflex arising from an inflation-induced stimulation of pulmonary C-fibers. We therefore recorded the impulse activity of 17 pulmonary C-fibers in barbiturate-anesthetized dogs with closed chests, while we placed the expiratory outlet of a ventilator under 5-30 cmH2O. Increasing PEEP in a ramp-like manner stimulated 12 of the 17 pulmonary C-fibers, with activity increasing from 0.0 +/- 0.1 to 0.9 +/- 0.2 imp/s when end-expiratory pressure equaled 15 cmH2O. When PEEP was increased in a stepwise manner to 15-20 cmH2O and maintained at this pressure for 15 min, pulmonary C-fibers increased their firing rates, but the effect was small averaging 0.2-0.3 imp/s after the 1st min of this maneuver. We conclude that pulmonary C-fibers are unlikely to be responsible for causing much of the decreases in cardiac output and arterial pressure evoked by sustained periods of PEEP in both patients and laboratory animals. These C-fibers, however, are likely to be responsible for causing the reflex decreases in these variables evoked by sudden application of PEEP.     

Response of slowly adapting pulmonary stretch receptors to reduced lung compliance

We examined the steady-state response of slowly adapting pulmonary stretch receptors (SAPSRs) to reduced lung compliance in open-chest cats with lungs ventilated at eupneic rate and tidal volume (VT) and with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. Transient removal of PEEP decreased compliance by approximately 30% and increased transpulmonary pressure (Ptp) by 1-2.5 cmH2O. Reduction of compliance significantly decreased SAPSR discharge in deflation and caused a small increase in discharge at the peak of inflation; it had little effect on discharge averaged over the ventilatory cycle. Increasing VT to produce a comparable increase in Ptp significantly increased peak discharge. Thus unlike rapidly adapting receptors, whose discharge is increased more effectively by reduced compliance than by increased VT, SAPSRs are stimulated by increased VT but not by reduced compliance. We speculate that the most consistent effect of reduced compliance on SAPSRs (the decrease in deflation discharge) was due to the decreased time constant for deflation in the stiffer lung. This alteration in firing may contribute to the tachypnea evoked as the lungs become stiffer.     

Increased lung expansion alters lung growth but not alveolar epithelial cell differentiation in newborn lambs

Although increased lung expansion markedly alters lung growth and epithelial cell differentiation during fetal life, the effect of increasing lung expansion after birth is unknown. We hypothesized that increased basal lung expansion, caused by ventilating newborn lambs with a positive end-expiratory pressure (PEEP), would stimulate lung growth and alter alveolar epithelial cell (AEC) proportions and decrease surfactant protein mRNA levels. Two groups of lambs were sedated and ventilated with either 0 cmH(2)O PEEP (controls, n = 5) or 10 cmH(2)O PEEP (n = 5) for 48 h beginning at 15 +/- 1 days after normal term birth. A further group of nonventilated 2-wk-old lambs was used for comparison. We determined wet and dry lung weights, DNA and protein content, a labeling index for proliferating cells, surfactant protein mRNA expression, and proportions of AECs using electron microscopy. Although ventilating lambs for 48 h with 10 cmH(2)O PEEP did not affect total lung DNA or protein, it significantly increased the proportion of proliferating cells in the lung when compared with nonventilated 2-wk-old controls and lambs ventilated with 0 cmH(2)O PEEP (control: 2.6 +/- 0.5%; 0 PEEP: 1.9 +/- 0.3%; 10 PEEP: 3.5 +/- 0.3%). In contrast, no differences were observed in AEC proportions or surfactant protein mRNA levels between either of the ventilated groups. This study demonstrates that increases in end-expiratory lung volumes, induced by the application of PEEP, lead to increased lung growth in mechanically ventilated 2-wk-old lambs but do not alter the proportions of AECs.     

Hemodynamic, gas exchange, and hormonal consequences of LBPP during PEEP ventilation

Hemodynamic, gas exchange, and hormonal response induced by application of a 25- to 40-mmHg lower body positive pressure (LBPP), during positive end-expiratory pressure (PEEP; 14 +/- 2.5 cmH2O) were studied in nine patients with acute respiratory failure. Compared with PEEP alone, LBPP increased cardiac index (CI) from 3.57 to 4.76 l X min-1 X m-2 (P less than 0.001) in relation to changes in right atrial pressure (RAP) (11 to 16 mmHg; P less than 0.01). Cardiopulmonary blood volume (CPBV) measured in five patients increased during LBPP from 546 +/- 126 to 664 +/- 150 ml (P less than 0.01), with a positive linear relationship between changes in RAP and CPBV (r = 0.88; P less than 0.001). Venous admixture (Qva/QT) decreased with PEEP from 24 to 16% (P less than 0.001) but did not change with LBPP despite the large increase in CI, leading to a marked O2 availability increase (P less than 0.001). Although PEEP induced a significant rise in plasma norepinephrine level (NE) (from 838 +/- 97 to 1008 +/- 139 pg/ml; P less than 0.05), NE was significantly decreased by LBPP to control level (from 1,008 +/- 139 to 794 +/- 124 pg/ml; P less than 0.003). Plasma epinephrine levels were not influenced by PEEP or LBPP. Changes of plasma renin activity (PRA) paralleled those of NE. No change in plasma arginine vasopressin (AVP) was recorded. We concluded that LBPP increases venous return and CPBV and counteracts hemodynamic effects of PEEP ventilation, without significant change in Qva/QT. Mechanical ventilation with PEEP stimulates sympathetic activity and PRA apparently by a reflex neuronal mechanism, at least partially inhibited by the loading of cardiopulmonary low-pressure reflex and high-pressure baroreflex. Finally, AVP does not appear to be involved in the acute cardiovascular adaptation to PEEP.     

Effect of dehydration on interstitial pressures in the isolated dog lung

We have determined the effect of dehydration on regional lung interstitial pressures. We stopped blood flow in the isolated blood-perfused lobe of dog lung at vascular pressure of approximately 4 cmH2O. Then we recorded interstitial pressures by micropuncture at alveolar junctions (Pjct), in perimicrovascular adventitia (Padv), and at the hilum (Phil). After base-line measurements, we ventilated the lobes with dry gas to decrease extravascular lung water content by 14 +/- 5%. In one group (n = 10), at constant inflation pressure of 7 cmH2O, Pjct was 0.2 +/- 0.8 and Padv was -1.5 +/- 0.6 cmH2O. After dehydration the pressures fell to -5.0 +/- 1.0 and -5.3 +/- 1.3 cmH2O, respectively (P less than 0.01), and the junction-to-advential gradient (Pjct-Padv) was abolished. In a second group (n = 6) a combination of dehydration and lung expansion with inflation pressure of 15 cmH2O further decreased Pjct and Padv to -7.3 +/- 0.7 and -7.1 +/- 0.7 cmH2O, respectively. Phil followed changes in Padv. Interstitial compliance was 0.6 at the junctions, 0.8 in adventitia, and 0.9 ml.cmH2O-1.100 g-1 wet lung at the hilum. We conclude, that perialveolar interstitial pressures may provide an important mechanism for prevention of lung dehydration.     

Rapidly adapting receptor activity in dogs is inversely related to lung compliance

We examined the response of pulmonary rapidly adapting receptors (RAR's) to changes in dynamic lung compliance (Cdyn) in the physiological range. RAR impulse activity was recorded from the cervical vagus nerves in anesthetized open-chest dogs whose lungs were ventilated at constant rate and tidal volume (VT), with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. After hyperinflation to produce maximal Cdyn, RAR's were silent or fired sparsely and irregularly. Reducing Cdyn in steps by briefly removing PEEP increased firing proportionately, and RAR's began to discharge vigorously in inflation. Activity was restored to control by hyperinflating the lungs. Activity also increased when we increased inflation rate, and hence the rate of change of airway pressure (dP/dt), by reducing inflation time, keeping VT and cycle length constant. RAR's were stimulated more when dP/dt was increased by reducing compliance than when dP/dt was increased by increasing inflation rate. We conclude that RAR's are sensitive to changes in Cdyn and speculate that excitatory input from RAR's may help to maintain VT as the lungs become stiffer.     

On-line monitoring of intrinsic PEEP in ventilator-dependent patients.

Measurement of the intrinsic positive end-expiratory pressure (PEEP(i)) is important in planning the management of ventilated patients. Here, a new recursive least squares method for on-line monitoring of PEEP(i) is proposed for mechanically ventilated patients. The procedure is based on the first-order model of respiratory mechanics applied to experimental measurements obtained from eight ventilator-dependent patients ventilated with four different ventilatory modes. The model PEEP(i) (PEEP(i,mod)) was recursively constructed on an inspiration-by-inspiration basis. The results were compared with two well-established techniques to assess PEEP(i): end-expiratory occlusion to measure static PEEP(i) (PEEP(i, st)) and change in airway pressure preceding the onset of inspiratory airflow to measure dynamic PEEP(i) (PEEP(i,dyn)). PEEP(i, mod) was significantly correlated with both PEEP(i,dyn) (r = 0.77) and PEEP(i,st) (r = 0.90). PEEP(i,mod) (5.6 +/- 3.4 cmH(2)O) was systematically >PEEP(i,dyn) and PEEP(i,st) (2.7 +/- 1.9 and 8.1 +/- 5.5 cmH(2)O, respectively), in all the models without external PEEP. Focusing on the five patients with chronic obstructive pulmonary disease, PEEP(i,mod) was significantly correlated with PEEP(i,st) (r = 0.71), whereas PEEP(i,dyn) (r = 0.22) was not. When PEEP was set 5 cmH(2)O above PEEP(i,st), all the methods correctly estimated total PEEP, i.e., 11.8 +/- 5.3, 12.5 +/- 5.0, and 12.0 +/- 4.7 cmH(2)O for PEEP(i,mod), PEEP(i,st), and PEEP(i,dyn), respectively, and were highly correlated (0.97-0.99). We interpreted PEEP(i,mod) as the lower bound of PEEP(i,st) and concluded that our method is suitable for on-line monitoring of PEEP(i) in mechanically ventilated patients.     

Effect of alveolar and pleural pressures on interstitial pressures in isolated dog lungs

We report the first direct measurements of perialveolar interstitial pressures in lungs inflated with negative pleural pressure. In eight experiments, we varied surrounding (pleural) pressure in a dog lung lobe to maintain constant inflation with either positive alveolar and ambient atmospheric pleural pressures (positive inflation) or ambient atmospheric alveolar and negative pleural pressures (negative inflation). Throughout, vascular pressure was approximately 4 cmH2O above pleural pressure. By the micropuncture servo-null technique we recorded interstitial pressures at alveolar junctions (Pjct) and in the perimicrovascular adventitia (Padv). At transpulmonary pressure of 7 cmH2O (n = 4), the difference of Pjct and Pady from pleural pressure of 0.9 +/- 0.4 and -1.1 +/- 0.2 cmH2O, respectively, during positive inflation did not significantly change (P less than 0.05) after negative inflation. After increase of transpulmonary pressure from 7 to 15 cmH2O (n = 4), the decrease of Pjct by 3.3 +/- 0.3 cmH2O and Pady by 2.0 +/- 0.4 cmH2O during positive inflation did not change during negative inflation. The Pjct-Pady gradient was not affected by the mode of inflation. Our measurements indicate that, in lung, when all pressures are referred to pleural or alveolar pressure, the mode of inflation does not affect perialveolar interstitial pressures.     

Effect of inspiratory resistance and PEEP on 99mTc-DTPA clearance

Experiments were performed to determine the effect of markedly negative pleural pressure (Ppl) or positive end-expiratory pressure (PEEP) on the pulmonary clearance (k) of technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). A submicronic aerosol containing 99mTc-DTPA was insufflated into the lungs of anesthetized intubated sheep. In six experiments k was 0.44 +/- 0.46% (SD)/min during the initial 30 min and was unchanged during the subsequent 30-min interval [k = 0.21 +/- 12%/min] when there was markedly increased inspiratory resistance. A 3-mm-diam orifice in the inspiratory tubing created the resistance. It resulted on average in a 13-cmH2O decrease in inspiratory Ppl. In eight additional experiments sheep were exposed to 2, 10, and 15 cmH2O PEEP (20 min at each level). During 2 cmH2O PEEP k = 0.47 +/- 0.15%/min, and clearance increased slightly at 10 cmH2O PEEP [0.76 +/- 0.28%/min, P less than 0.01]. When PEEP was increased to 15 cmH2O a marked increase in clearance occurred [k = 1.95 +/- 1.08%/min, P less than 0.001]. The experiments demonstrate that markedly negative inspiratory pressures do not accelerate the clearance of 99mTc-DTPA from normal lungs. The effect of PEEP on k is nonlinear, with large effects being seen only with very large increases in PEEP.     

Reflex mechanisms for changes in renal nerve activity during positive end-expiratory pressure

This study was designed to investigate the interaction between carotid sinus baroreceptors and cardiopulmonary receptors in the reflex control of renal nerve activity (RNA) during positive end-expiratory pressure (PEEP) in anesthetized dogs. PEEP at two different levels (10 and 20 cmH2O) was applied to the following groups: animals with neuraxis intact (I group, n = 12); vagal and aortic nerve denervated animals with carotid sinus nerves intact (V group, n = 6); carotid sinus denervated animals with vagal and aortic nerves intact (SD group, n = 6); and carotid sinus denervated animals also having severed vagal and aortic nerves (SAV group, n = 12). Mean blood pressure (MBP), central venous pressure, and mean airway pressure were also simultaneously measured. In the I group, no significant alterations in RNA occurred during PEEP at both levels, even when MBP fell significantly. Although the drop in MBP in the SD group was similar to that in the I group, RNA decreased significantly 10 s after intervention at both PEEP levels, followed by a recovery of RNA toward the control level. In contrast, a significant increase in RNA, which continued until the end of PEEP, appeared in the V group immediately after each intervention. In the SAV group, RNA responses to PEEP, which were observed in the other groups, were abolished. These results provide evidence that during PEEP, renal nerve activity is modified by an interaction between carotid sinus baroreceptors and cardiopulmonary receptors; excitatory effects occur via carotid sinus nerves and inhibitory effects occur via vagal afferents.     

Afferent neural pathways in cough and reflex bronchoconstriction

Cough and bronchoconstriction are airway reflexes that protect the lung from inspired noxious agents. These two reflexes can be evoked both from the larynx and tracheobronchial tree and also from some extrarespiratory sites. Within the airways, certain sites are particularly sensitive to stimulation of cough (larynx and points of proximal airway branching), whereas bronchoconstriction can be triggered from the whole of the tracheobronchial tree. In the larynx, "irritant" receptors with myelinated afferents mediate cough and bronchoconstriction. Little seems to be known about laryngeal nonmyelinated afferents and their reflexes. In the tracheobronchial tree and lung, slowly adapting stretch receptors (SARs) and rapidly adapting stretch receptors (RARs) have opposing effects on airway tone, the former mediating bronchodilation and the latter bronchoconstriction. In cough, on the other hand, they operate concurrently, a mediatory role for RARs and a facilitatory role for SARs. C-fiber endings (bronchial and pulmonary) mediate bronchoconstriction. Inhalation of so-called "selective" C-fiber stimulants induces cough, but excitation of RARs has not been eliminated, and the possibility also exists that the cough is secondary to other lung actions mediated by these nerve endings. Although cough and bronchoconstriction may be mediated by the same type of receptor, they seem to have separate afferent neural pathways.     

Effects of PEEP on pulmonary hemodynamics in intact dogs with oleic acid pulmonary edema

The effects of positive end-expiratory pressure (PEEP) on the pulmonary circulation were studied in 14 intact anesthetized dogs with oleic acid (OA) lung injury. Transmural (tm) mean pulmonary arterial pressure (Ppa)/cardiac index (Q) plots with transmural left atrial pressure (Pla) kept constant were constructed in seven dogs, and Ppa(tm)/PEEP plots with Q and Pla(tm) kept constant were constructed in seven other dogs. Q was manipulated by using a femoral arteriovenous bypass and a balloon catheter inserted in the inferior vena cava. Pla was manipulated using a balloon catheter placed by thoracotomy in the left atrium. Ppa(tm)/Q plots were essentially linear. Before OA, the linearly extrapolated pressure intercept of the Ppa(tm)/Q relationship approximated Pla(tm). OA (0.09 ml/kg into the right atrium) produced a parallel shift of the Ppa(tm)/Q relationship to higher pressures; i.e., the extrapolated pressure intercept increased while the slope was not modified. After OA, 4 Torr PEEP (5.4 cmH2O) had no effect on the Ppa(tm)/Q relationship and 10 Torr PEEP (13.6 cmH2O) produced a slight, not significant, upward shift of this relationship. Changing PEEP from 0 to 12 Torr (16.3 cmH2O) at constant Q before OA led to an almost linear increase of Ppa(tm) from 14 +/- 1 to 19 +/- 1 mmHg. After OA, Ppa(tm) increased at 0 Torr PEEP but changing PEEP from 0 to 12 Torr did not significantly affect Ppa(tm), which increased from 19 +/- 1 to 20 +/- 1 mmHg. These data suggest that moderate levels of PEEP minimally aggravate the pulmonary hypertension secondary to OA lung injury.     

Comparison of lung protection strategies using conventional and high-frequency oscillatory ventilation.

This study compared pathophysiological and biochemical indexes of acute lung injury in a saline-lavaged rabbit model with different ventilatory strategies: a control group consisting of moderate tidal volume (V(T)) (10-12 ml/kg) and low positive end-expiratory pressure (PEEP) (4-5 cmH(2)O); and three protective groups: 1) low V(T) (5-6 ml/kg) high PEEP, 2-3 cmH(2)O greater than the lower inflection point; 2) low V(T) (5-6 ml/kg), high PEEP (8-10 cmH(2)O); and 3) high-frequency oscillatory ventilation (HFOV). The strategy using PEEP > inflection point resulted in hypotension and barotrauma. HFOV attenuated the decrease in pulmonary compliance, the lung inflammation assessed by polymorphonuclear leukocyte infiltration and tumor necrosis factor-alpha concentration in the alveolar space, and pathological changes of the small airways and alveoli. Conventional mechanical ventilation using lung protection strategies (low V(T) high PEEP) only attenuated the decrease in oxygenation and pulmonary compliance. Therefore, HFOV may be a preferable option as a lung protection strategy.     

Dependence of lung injury on inflation rate during low-volume ventilation in normal open-chest rabbits.

Lung mechanics and morphometry were assessed in two groups of nine normal open-chest rabbits mechanically ventilated (MV) for 3-4 h at zero end-expiratory pressure (ZEEP) with physiological tidal volumes (Vt; 11 ml/kg) and high (group A) or low (group B) inflation flow (44 and 6.1 ml x kg(-1) x s(-1), respectively). Relative to initial MV on positive end-expiratory pressure (PEEP; 2.3 cmH(2)O), MV on ZEEP increased quasi-static elastance and airway and viscoelastic resistance more in group A (+251, +393, and +225%, respectively) than in group B (+180, +247, and +183%, respectively), with no change in viscoelastic time constant. After restoration of PEEP, quasi-static elastance and viscoelastic resistance returned to control, whereas airway resistance, still relative to initial values, remained elevated more in group A (+86%) than in group B (+33%). In contrast, prolonged high-flow MV on PEEP had no effect on lung mechanics of seven open-chest rabbits (group C). Gas exchange on PEEP was equally preserved in all groups, and the lung wet-to-dry ratios were normal. Relative to group C, both groups A and B had an increased percentage of abnormal alveolar-bronchiolar attachments and number of polymorphonuclear leukocytes in alveolar septa, the latter being significantly larger in group A than in group B. Thus prolonged MV on ZEEP with cyclic opening-closing of peripheral airways causes alveolar-bronchiolar uncoupling and parenchymal inflammation with concurrent, persistent increase in airway resistance, which are worsened by high-inflation flow.     

Different ventilation strategies alter surfactant responses in preterm rabbits.

The effect of ventilation strategy on in vivo function of different surfactants was evaluated in preterm rabbits delivered at 27 days gestational age and ventilated with either 0 cmH2O positive end-expiratory pressure (PEEP) at tidal volumes of 10-11 ml/kg or 3 cmH2O PEEP at tidal volumes of 7-8 ml/kg after treatment with one of four different surfactants: sheep surfactant, the lipids of sheep surfactant stripped of protein (LH-20 lipid), Exosurf, and Survanta. The use of 3 cmH2O PEEP decreased pneumothoraces in all groups except for the sheep surfactant group where pneumothoraces increased (P < 0.01). Ventilatory pressures (peak pressures - PEEP) decreased more with the 3 cmH2O PEEP, low-tidal-volume ventilation strategy for Exosurf-, Survanta-, and sheep surfactant-treated rabbits (P < 0.05), whereas ventilation efficiency indexes (VEI) improved only for Survanta- and sheep surfactant-treated rabbits with 3 cmH2O PEEP (P < 0.01). Pressure-volume curves for sheep surfactant-treated rabbits were better than for all other treated groups (P < 0.01), although Exosurf and Survanta increased lung volumes above those in control rabbits (P < 0.05). The recovery of intravascular radiolabeled albumin in the lungs and alveolar washes was used as an indicator of pulmonary edema. Only Survanta and sheep surfactant decreased protein leaks in the absence of PEEP, whereas all treatments decreased labeled albumin recoveries when 3 cmH2O PEEP was used (P < 0.05). These experiments demonstrate that ventilation style will alter a number of measurements of surfactant function, and the effects differ for different surfactants.     

Changes in upper airway resistance with lung inflation and positive airway pressure

The influence of pulmonary inflation and positive airway pressure on nasal and pharyngeal resistance were studied in 10 normal subjects lying in an iron lung. Upper airway pressures were measured with two low-bias flow catheters while the subjects breathed by the nose through a Fleish no. 3 pneumotachograph into a spirometer. Resistances were calculated at isoflow rates in four different conditions: exclusive pulmonary inflation, achieved by applying a negative extra-thoracic pressure (NEP); expiratory positive airway pressure (EPAP), which was created by immersion of the expiratory line; continuous positive airway pressure (CPAP), realized by loading the bell of the spirometer; and CPAP without pulmonary inflation by simultaneously applying the same positive extrathoracic pressure (CPAP + PEP). Resistance measurements were obtained at 5- and 10-cmH2O pressure levels. Pharyngeal resistance (Rph) significantly decreased during each measurement; the decreases in nasal resistance were only significant with CPAP and CPAP + PEP; the deepest fall in Rph occurred with CPAP. It reached 70.8 +/- 5.5 and 54.8 +/- 6.5% (SE) of base-line values at 5 and 10 cmH2O, respectively. The changes in lung volume recorded with CPAP + PEP ranged from -180 to 120 ml at 5 cmH2O and from -240 to 120 ml at 10 cmH2O. Resistances tended to increase with CPAP + PEP compared with CPAP values, but these changes were not significant (Rph = 75.9 +/- 6.1 and 59.9 +/- 6.6% at 5 and 10 cmH2O of CPAP + PEP). We conclude that 1) the upper airway patency increases during pulmonary inflation, 2) the main effect of CPAP is related to pneumatic splinting, and 3) pulmonary inflation contributes little to the decrease in upper airways resistance observed with CPAP.