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.     

Effects of positive end-expiratory pressure on the right ventricle

Transmural cardiac pressures, stroke volume, right ventricular volume, and lung water content were measured in normal dogs and in dogs with oleic acid-induced pulmonary edema (PE) maintained on positive-pressure ventilation. Measurements were performed prior to and following application of 20 cmH2O positive end-expiratory pressure (PEEP). Colloid fluid was given during PEEP for ventricular volume expansion before and after the oleic acid administration. PEEP significantly increased pleural pressure and pulmonary vascular resistance but decreased right ventricular volume, stroke volume, and mean arterial pressure in both normal and PE dogs. Although the fluid infusion during PEEP raised right ventricular diastolic volumes to the pre-PEEP level, the stroke volumes did not significantly increase in either normal dogs or the PE dogs. The fluid infusion, however, significantly increased the lung water content in the PE dogs. Following discontinuation of PEEP, mean arterial pressure, cardiac output, and stroke volume significantly increased, and heart rate did not change. The failure of the stroke volume to increase despite significant right ventricular volume augmentation during PEEP indicates that positive-pressure ventilation with 20 cmH2O PEEP decreases right ventricular function.     

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.     

Hemodynamic effects of PEEP applied as a ramp in normo-, hyper-, and hypovolemia

Nonlinear hemodynamic responses on positive end-expiratory pressure (PEEP) have been attributed to a rise of mean central venous pressure (Pcv), to compensatory cardiovascular control mechanisms, and to the occurrence of a lung stretch depressor reflex above a threshold lung stretch. We tested the hypothesis that the contribution of each of these mechanisms is dependent on the preexisting volemic load. PEEP was applied as a continuous rise (ramp) in piglets in three different volemic loads. In the normovolemic circulation cardiac output (CO) decreased nonlinearly in three phases during the PEEP ramp up to 15 cmH2O. CO decreased gradually in phase I, followed by a sharp decrease in phase II between a PEEP of 3 and 9 cmH2O and again a more gradual decrease in phase III up to a PEEP of 15 cmH2O. Heart rate (HR) and mean aortic pressure (PaO) also decreased during phase II, indicating the predominance of a lung stretch depressor reflex. In the hypervolemic circulation (loading 15 ml . kg-1 dextran) only phases I and II were observed with the onset of phase II at a higher level of PEEP (6 cmH2O). More lung stretch appeared to be necessary to elicit the lung stretch depressor reflex. In the hypovolemic circulation (hemorrhage 15 ml . kg-1) CO decreased linearly, Pao was stable after an initial decrease, and HR increased continuously, indicating a predominance of cardiovascular compensatory mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Relationship of end-expiratory pressure, lung volume, and 99mTc-DTPA clearance

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH2O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH2O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH2O PEEP. At 2.5 cmH2O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH2O (P less than 0.05). Between 15 and 20 cmH2O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized 99mTc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation.     

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 negative-pressure ventilation on lung water in permeability pulmonary edema

We have previously shown (Am. Rev. Respir. Dis. 136: 886-891, 1987) improved cardiac output in dogs with pulmonary edema ventilated with external continuous negative chest pressure ventilation (CNPV) using negative end-expiratory pressure (NEEP), compared with continuous positive-pressure ventilation (CPPV) using equivalent positive end-expiratory pressure (PEEP). The present study examined the effect on lung water of CNPV compared with CPPV to determine whether the increased venous return created by NEEP worsened pulmonary edema in dogs with acute lung injury. Oleic acid (0.06 ml/kg) was administered to 27 anesthetized dogs. Supine animals were then divided into three groups and ventilated for 6 h. The first group (n = 10) was treated with intermittent positive-pressure ventilation (IPPV) alone; the second (n = 9) received CNPV with 10 cmH2O NEEP; the third (n = 8) received CPPV with 10 cmH2O PEEP. CNPV and CPPV produced similar improvements in oxygenation over IPPV. However, cardiac output was significantly depressed by CPPV, but not by CNPV, when compared with IPPV. Although there were no differences in extravascular lung water (Qwl/dQl) between CNPV and CPPV, both significantly increased Qwl/dQl compared with IPPV (7.81 +/- 0.21 and 7.87 +/- 0.31 vs. 6.71 +/- 0.25, respectively, P less than 0.01 in both instances). CNPV and CPPV, but not IPPV, enhanced lung water accumulation in the perihilar areas where interstitial pressures may be most negative at higher lung volumes.     

Combination of constant-flow and continuous positive-pressure ventilation in canine pulmonary edema

Constant-flow ventilation (CFV) maintains alveolar ventilation without tidal excursion in dogs with normal lungs, but this ventilatory mode requires high CFV and bronchoscopic guidance for effective subcarinal placement of two inflow catheters. We designed a circuit that combines CFV with continuous positive-pressure ventilation (CPPV; CFV-CPPV), which negates the need for bronchoscopic positioning of CFV cannula, and tested this system in seven dogs having oleic acid-induced pulmonary edema. Addition of positive end-expiratory pressure (PEEP, 10 cmH2O) reduced venous admixture from 44 +/- 17 to 10.4 +/- 5.4% and kept arterial CO2 tension (PaCO2) normal. With the innovative CFV-CPPV circuit at the same PEEP and respiratory rate (RR), we were able to reduce tidal volume (VT) from 437 +/- 28 to 184 +/- 18 ml (P less than 0.001) and elastic end-inspiratory pressures (PEI) from 25.6 +/- 4.6 to 17.7 +/- 2.8 cmH2O (P less than 0.001) without adverse effects on cardiac output or pulmonary exchange of O2 or CO2; indeed, PaCO2 remained at 35 +/- 4 Torr even though CFV was delivered above the carina and at lower (1.6 l.kg-1.min-1) flows than usually required to maintain eucapnia during CFV alone. At the same PEEP and RR, reduction of VT in the CPPV mode without CFV resulted in CO2 retention (PaCO2 59 +/- 8 Torr). We conclude that CFV-CPPV allows CFV to effectively mix alveolar and dead spaces by a small bulk flow bypassing the zone of increased resistance to gas mixing, thereby allowing reduction of the CFV rate, VT, and PEI for adequate gas exchange.     

Influence of lung volume and alveolar pressure on reverse pulmonary venous blood flow.

We have reported that left atrial blood refluxes through the pulmonary veins to gas-exchanging tissue after pulmonary artery ligation. This reverse pulmonary venous flow (Qrpv) was observed only when lung volume was changed by ventilation. This was believed to drive Qrpv by alternately distending and compressing the alveolar and extra-alveolar vessels. Because lung and pulmonary vascular compliances change with lung volume, we studied the effect of positive end-expiratory pressure (PEEP) on the magnitude of Qrpv during constant-volume ventilation. In prone anesthetized goats (n = 8), using the right lung to maintain normal blood gases, we ligated the pulmonary and bronchial arterial inflow to the left lung and ventilated each lung separately. A solution of SF6, an inert gas, was infused into the left atrium. SF6 clearance from the left lung was determined by the Fick principle at 0, 5, 10, and 15 and again at 0 cmH2O PEEP and was used to measure Qrpv. Left atrial pressure remained nearly constant at 20 cmH2O because the increasing levels of PEEP were applied to the left lung only. Qrpv was three- to fourfold greater at 10 and 15 than at 0 cmH2O PEEP. At these higher levels of PEEP, there were greater excursions in alveolar pressure for the same ventilatory volume. We believe that larger excursions in transpulmonary pressure during tidal ventilation at higher levels of PEEP, which compressed alveolar vessels, resulted in the reflux of greater volumes of left atrial blood, through relatively noncompliant extra-alveolar veins into alveolar corner vessels, and more compliant extra-alveolar arteries.     

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.     

Flow through zone 1 lungs utilizes alveolar corner vessels

We have previously observed flows equivalent to 15% of the resting cardiac output of rabbits occurring through isolated lungs that were completely in zone 1. To distinguish between alveolar corner vessels and alveolar septal vessels as a possible zone 1 pathway, we made in vivo microscopic observations of the subpleural alveolar capillaries in five anesthetized dogs. Videomicroscopic recordings were made via a transparent thoracic window with the animal in the right lateral position. From recordings of the uppermost surface of the left lung, alveolar septal and corner vessels were classified depending on whether they were located within or between alveoli, respectively. Observations were made with various levels of positive end-expiratory pressure (PEEP) applied only to the left lung via a double-lumen endotracheal tube. Consistent with convention, flow through septal vessels stopped when PEEP was raised to the mean pulmonary arterial pressure (the zone 1-zone 2 border). However, flow through alveolar corner vessels continued until PEEP was 8-16 cmH2O greater than mean pulmonary arterial pressure (8-16 cm into zone 1). These direct observations support the idea that alveolar corner vessels rather than patent septal vessels provide the pathway for blood flow under zone 1 conditions.     

Effect of different levels of positive end-expiratory pressure on lung water content

To compare the effects of 2-, 5-, and 10-cmH2O positive end-expiratory pressure (PEEP) on pulmonary extravascular water volume (PEWV), pulmonary blood volume (PBV), pulmonary dry weight (PDW), and distensibility, we separately ventilated perfused dogs' lungs in situ and produced pulmonary edema with oleic acid (0.06 ml/kg). Three groups were studied: I, PEEP, 5 cmH2O in both lung; II, PEEP, 2 cmH2O in one lung and 10 cmH2O in the other; and III, PEEP, same as II, but the chest was rotated to compensate for differences in heights. The PEWV and distensibility were less (P less than 0.05) in lungs exposed to 10-cmH2O than to either 2- or 5-cmH2O PEEP. After chest rotation, the difference between 10- and 2-cmH2O PEEP on PEWV was eliminated but that on distensibility was not. We conclude that 10-cmH2O PEEP 1) decreased water content because of lung volume-induced effects on intravascular hydrostatic pressure and 2) improved distensibility by recruitment of alveoli, irrespective of PEWV.     

Production mechanism of crackles in excised normal canine lungs

Lung crackles may be produced by the opening of small airways or by the sudden expansion of alveoli. We studied the generation of crackles in excised canine lobes ventilated in an airtight box. Total airflow, transairway pressure (Pta), transpulmonary pressure (Ptp), and crackles were recorded simultaneously. Crackles were produced only during inflation and had high-peak frequencies (738 +/- 194 Hz, mean +/- SD). During inflation, crackles were produced from 111 +/- 83 ms (mean +/- SD) prior to the negative peak of Pta, presumably when small airways began to open. When end-expiratory Ptp was set constant between 15 and 20 cmH2O and end-expiratory Ptp was gradually reduced from 5 cmH2O to -15 or -20 cmH2O in a breath-by-breath manner, crackles were produced in the cycles in which end-expiratory Ptp fell below -1 to 1 cmH2O. This pressure was consistent with previously known airway closing pressures. When end-expiratory Ptp was set constant at -10 cmH2O and end inspiratory Ptp was gradually increased from -5 to 15 or 20 cmH2O, crackles were produced in inspiratory phase in which end-inspiratory Ptp exceeded 4-6 cmH2O. This pressure was consistent with previously known airway opening pressures. These results indicate that crackles in excised normal dog lungs are produced by opening of peripheral airways and are not generated by the sudden inflation of groups of alveoli.     

Site of deposition and factors affecting clearance of aerosolized solute from canine lungs

We determined the influence of several factors on lung solute clearance using aerosolized 99mTc-diethylenetriaminepentaacetate. We used a jet nebulizer-plate separator-balloon system to generate particles with an activity median aerodynamic diameter of 1.1 micron, administered the aerosol in a standard fashion, and determined clearance half times (t1/2) with a gamma-scintillation camera. The following serial studies were performed in five anesthetized, paralyzed, intubated, mechanically ventilated dogs: 1) control, with ventilatory frequency (f) = 15 breaths/min and tidal volume (VT) = 15 ml/kg during solute clearance; 2) repeat control, for reproducibility; 3) increased frequency, with f = 25 breaths/min and VT = 10 ml/kg; 4) positive end-expiratory pressure (PEEP) of 10 cmH2O; 5) unilateral pulmonary arterial occlusion (PAO); and 6) bronchial arterial occlusion (BAO). Control t1/2 was 25 +/- 5 min and did not change in the repeat control, increased frequency, or BAO experiments. PEEP markedly decreased t1/2 to 13 +/- 3 min (P less than 0.01), and PAO increased it to 37 +/- 6 min (P less than 0.05). We conclude that clearance from the lungs by our method is uninfluenced by increased frequency, increases markedly with PEEP, and depends on pulmonary, not bronchial, blood flow.     

Spectrum of myelinated pulmonary afferents

Myelinated pulmonary afferents are classified as rapidly adapting receptors (RARs) or slowly adapting receptors (SARs) by their adaptation rate. Behavior of SARs varies greatly, and therefore the present study tries to further categorize SARs according to their mechanical properties. Single-fiber activity of 104 SARs was examined in anesthetized, open-chest, artificially ventilated rabbits. According to the increase or decrease in activity during removal of positive-end-expiratory pressure (PEEP), SARs were divided into two groups. In one group mean activity increased from 31 +/- 6 to 46 +/- 7 impulses per second (imp/s; n = 11); in another group mean activity decreased from 44 +/- 2 to 25 +/- 1 imp/s (n = 93). The first group of SARs has high adaptation indexes (RAR-like), which increased with inflation pressure (36 +/- 3, 44 +/- 3, and 47 +/- 3% for 10, 15, and 20 cmH(2)O, respectively; P < 0.005). Their peak activity shifted from inflation phase to deflation phase during PEEP removal. The second group of SARs has low-adaptation indexes (typical SARs), which were not affected by inflation pressure (19 +/- 1, 18 +/- 1, and 17 +/- 1% for 10, 15, and 20 cmH(2)O; P = 0. 516). Their peak activity did not shift during PEEP removal. Because there are overlaps in other characteristics, it is proposed that myelinated vagal afferents are viewed as a heterogeneous group; their behaviors are like a spectrum, where typical RARs and SARs represent two extremes of the spectrum. The receptor behavior might be determined by anatomic location and its environment.     

Splanchnic vascular capacitance and positive end-expiratory pressure in dogs

We have investigated the effect of positive end-expiratory pressure ventilation (PEEP) on regional splanchnic vascular capacitance. In 12 anesthetized dogs hepatic and splenic blood volumes were assessed by sonomicrometry. Vascular pressure-diameter curves were defined by obstructing hepatic outflow. With 10 and 15 cmH2O PEEP portal venous pressure increased 3.1 +/- 0.3 and 5.1 +/- 0.4 mmHg (P less than 0.001) while hepatic venous pressure increased 4.9 +/- 0.4 and 7.3 +/- 0.4 mmHg (P less than 0.001), respectively. Hepatic blood volume increased (P less than 0.01) 3.8 +/- 0.9 and 6.3 +/- 1.4 ml/kg body wt while splenic volume decreased (P less than 0.01) 0.8 +/- 0.2 and 1.3 +/- 0.2 ml/kg body wt. The changes were similar with closed abdomen. The slope of the hepatic vascular pressure-diameter curves decreased with PEEP (P less than 0.01), possibly reflecting reduced vascular compliance. There was an increase (P less than 0.01) in unstressed hepatic vascular volume. The slope of the splenic pressure-diameter curves was unchanged, but there was a significant (P less than 0.05) decrease in unstressed diameter during PEEP. In conclusion, hepatic blood volume increased during PEEP. This was mainly a reflection of passive distension due to elevated venous pressures. The spleen expelled blood and thus prevented a further reduction in central blood volume.     

The respiratory change in preejection period: a new method to predict fluid responsiveness.

The accuracy and clinical utility of preload indexes as bedside indicators of fluid responsiveness in patients after cardiac surgery is controversial. This study evaluates whether respiratory changes (Delta) in the preejection period (PEP; DeltaPEP) predict fluid responsiveness in mechanically ventilated patients. Sixteen postcoronary artery bypass surgery patients, deeply sedated under mechanical ventilation, were enrolled. PEP was defined as the time interval between the beginning of the Q wave on the electrocardiogram and the upstroke of the radial arterial pressure. DeltaPEP (%) was defined as the difference between expiratory and inspiratory PEP measured over one respiratory cycle. We also measured cardiac output, stroke volume index, right atrial pressure, pulmonary arterial occlusion pressure, respiratory change in pulse pressure, systolic pressure variation, and the Deltadown component of SPV. Data were measured without positive end-expiratory pressure (PEEP) and after application of a PEEP of 10 cmH2O (PEEP10). When PEEP10 induced a decrease of >15% in mean arterial pressure value, then measurements were re-performed before and after volume expansion. Volume loading was done in eight patients. Right atrial pressure and pulmonary arterial occlusion pressure before volume expansion did not correlate with the change in stroke volume index after the fluid challenge. Systolic pressure variation, DeltaPEP, Deltadown, and change in pulse pressure before volume expansion correlated with stroke volume index change after fluid challenge (r2 = 0.52, 0.57, 0.68, and 0.83, respectively). In deeply sedated, mechanically ventilated patients after cardiac surgery, DeltaPEP, a new method, can be used to predict fluid responsiveness and hemodynamic response to PEEP10.     

Effect of ventilation and perfusion imbalance on inert gas rebreathing variables

The effects of ventilation-to-perfusion (VA/Qc) maldistribution within the lungs on measured multiple gas rebreathing variables were studied in 14 dogs. The rebreathing method (using He, C18O, and C2H2) allows for measurements of pulmonary capillary blood flow (Qc), diffusing capacity (DLco), lung gas volume, and the combined pulmonary tissue and capillary blood volume (VTPC). VA/Qc imbalance was created by reversibly occluding the right main pulmonary artery or by reversibly obstructing the left main bronchus in eight dogs. Six additional dogs were ventilated with 10 cmH2O positive end-expiratory pressure (PEEP) to create a bimodal distribution of VA/Qc within the lungs. No significant alterations in computed rebreathing variables, except for a small (14%) decrease in DLco, occurred during right main pulmonary artery occlusion, whereas obstruction of the left main bronchus caused parallel decreases (mean of 46%) in all rebreathing variables. Ventilation with 10 cmH2O PEEP for 3 h caused no alterations in VTPC when compared with postmortem determinations of total lung water. Thus marked alterations in distribution of Qc or creation of VA/Qc maldistributions with PEEP caused no significant changes in rebreathing parameters, whereas obstruction of the left main bronchus resulted in decreases in all rebreathing values consistent with the presumed size of the ventilation defect. Thus it appears that rebreathing estimates of VTPC and other rebreathing parameters are accurate in states of moderate VA/Qc maldistribution within the lung.     

PEEP is necessary for exogenous surfactant to reduce pulmonary edema in canine aspiration pneumonitis.

Alveolar edema inactivates surfactant, and surfactant depletion causes edema by reducing lung interstitial pressure (Pis). We reasoned that surfactant repletion might reduce edema by raising Pis after acute lung injury and that positive end-expiratory pressure (PEEP) might facilitate this effect. One hour after tracheal administration of hydrochloric acid in 18 anesthetized dogs with transmural pulmonary capillary wedge pressure of 8 Torr, the animals were randomized into three groups: in the SURF + PEEP group, 50 mg/kg of calf lung surfactant extract (CLSE) was instilled into each main stem bronchus with 8 cmH2O of PEEP; in the SAL + PEEP group, PEEP was followed by an equal volume of saline (SAL); in the SURF group, CLSE was given without PEEP. After 5 h, edema in excised lungs (wet-to-dry weight ratios) was significantly less in the SURF + PEEP group (9.1 +/- 1.0) than in the other groups (11.3 +/- 1.8 and 11.3 +/- 1.8, respectively). In the SURF + PEEP group, pulmonary venous admixture fell by 6%; this change was different from the 7% increase in the SAL + PEEP group and 40% increase in the SURF group (P less than 0.05). Airway secretions obtained in the SURF + PEEP group had normal minimum surface tensions of 4 +/- 2 mN/m, a value much lower than in SAL + PEEP and SURF groups (32 +/- 4 and 22 +/- 7 mN/m, respectively). We conclude that surfactant normalizes surface tension and decreases transcapillary hydrostatic forces in this lung injury model, thereby reducing edema formation and improving gas exchange. These benefits occur only if surfactant is given with PEEP, allowing surfactant access to the alveoli and/or minimizing its inhibition by edema proteins.