High-frequency ventilation for acute lung injury and ARDS.

In patients with acute lung injury (ALI) and ARDS, conventional mechanical ventilation (CV) may cause additional lung injury from overdistention of the lung during inspiration, repeated opening and closing of small bronchioles and alveoli, or from excessive stress at the margins between aerated and atelectatic lung regions. Increasing evidence suggests that smaller tidal volumes (VTs) and higher end-expiratory lung volumes (EELVs) may be protective from these forms of ventilator-associated lung injury and may improve outcomes from ALI/ARDS. High-frequency ventilation (HFV)-based ventilatory strategies offer two potential advantages over CV for patients with ALI/ARDS. First, HFV uses very small VTs, allowing higher EELVs with less overdistention than is possible with CV. Second, despite the small VTs, high respiratory rates during HFV allow the maintenance of normal or near-normal PaCO2 levels. In this review, the use of HFV as a lung protective strategy for patients with ALI/ARDS is discussed.

CPAP reduces inspiratory work more than dyspnea during hyperinflation with intrinsic PEEP.

Hyperinflation with intrinsic positive end-expiratory pressure (PEEPi) loads the respiratory muscles and causes dyspnea in obstructive lung disease. Continuous positive airway pressure (CPAP) has shown some efficacy in reducing inspiratory work and dyspnea. However, in obstructive lung disease, inspiratory work and dyspnea may be increased by additional factors that may not be affected by CPAP. Therefore, to study the effects of hyperinflation with intrinsic PEEP and CPAP in isolation, we used a mechanical analog of airway closure to increase end-expiratory lung volume in normal subjects. In five subjects in whom inspiratory work was measured, increasing end-expiratory lung volume by 1 and 2 L increased inspiratory work per breath from 0.42 +/- 0.04 J to 1.17 +/- 0.15 J (p < 0.05 compared with baseline) and 1.58 +/- 0.22 J (p < 0.05 compared with baseline and to the lesser level of hyperinflation). Although CPAP reduced work per breath and per minute to levels not significantly different from baseline, it had little effect on dyspnea. In ten subjects hyperinflated to 2.4 +/- 0.12 L above FRC, breathing could be sustained 19.5 +/- 4.5 min before quitting the load. This was increased to 26.7 +/- 5.2 min by 10 cm H2O CPAP (p = 0.052). Inspiratory dyspnea was modestly reduced by CPAP during these endurance trials. We conclude that CPAP can substantially ameliorate the respiratory work load induced by hyperinflation with intrinsic PEEP. However, the effects of CPAP on dyspnea and endurance are more limited. This suggests that the limits to breathing at high lung volumes are related to factors in addition to respiratory muscle work, and that CPAP may be of more value in reducing the work than in relieving the distress of obstructive lung disease.

Diagnosis of tracheoesophageal fistula by analysis of gastric air.

Two patients receiving positive pressure ventilation experienced marked gaseous abdominal distension. Analysis of gases from the stomach, ventilator, and room air suggested that the gastric gases came from the ventilator in one patient. The diagnosis of tracheoesophageal fistula was confirmed by esophagoscopy. Analysis of gases in the other patient did not support the suspicion of tracheoesophageal fistula, and no fistula was found at autopsy. The technique of gastric air analysis is presented as a simple supporting tool for the clinical diagnosis of tracheoesophageal fistula in patients receiving positive pressure ventilation.

Treatment of ARDS.

Improved understanding of the pathogenesis of acute lung injury (ALI)/ARDS has led to important advances in the treatment of ALI/ARDS, particularly in the area of ventilator-associated lung injury. Standard supportive care for ALI/ARDS should now include a protective ventilatory strategy with low tidal volume ventilation by the protocol developed by the National Institutes of Health ARDS Network. Further refinements of the protocol for mechanical ventilation will occur as current and future clinical trials are completed. In addition, novel modes of mechanical ventilation are being studied and may augment standard therapy in the future. Although results of anti-inflammatory strategies have been disappointing in clinical trials, further trials are underway to test the efficacy of late corticosteroids and other approaches to modulation of inflammation in ALI/ARDS.

Flow-volume characteristics in the pulmonary circulation.

Isolated ferret and canine lungs were used to validate a method for assessing determinants of vascular volume in the pulmonary circulation. With left atrial pressure (Pla) constant at 5 mmHg, flow (Q) was raised in steps over a physiological range. Changes in vascular volume (delta V) with each increment in Q were determined as the opposite of changes in perfusion system reservoir weight or from the increase in lung weight. At each level of Q, the pulmonary arterial and left atrial cannulas were simultaneously occluded, allowing all vascular pressures to equilibrate at the same static pressure (Ps), which was equal to the compliance-weighted average pressure in the circulation before occlusion. Hypoxia (inspired PO2 25 Torr) in ferret lungs, which causes intense constriction in arterial extra-alveolar vessels, had no effect on the slope of the Ps-Q relationship, interpreted to represent the resistance downstream from compliance (control 0.025 +/- 0.006 mmHg.ml-1.min, hypoxia 0.030 +/- 0.013). The Ps-axis intercept increased from 8.94 +/- 0.50 to 13.43 +/- 1.52 mmHg, indicating a modest increase in the effective back-pressure to flow downstream from compliant regions. The compliance of the circulation, obtained from the slope of the relationship between delta V and Ps, was unaffected by hypoxia (control 0.52 +/- 0.08 ml/mmHg, hypoxia 0.56 +/- 0.08). In contrast, histamine in canine lungs, which causes constriction in veins, caused the slope of the Ps-Q relationship to increase from 0.013 +/- 0.007 to 0.032 +/- 0.006 mmHg.ml-1.min (P less than 0.05) and the compliance to decrease from 3.51 +/- 0.56 to 1.68 +/- 0.37 ml/mmHg (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of reduced LV afterload by systolic and diastolic positive pleural pressure.

To investigate the mechanism by which increased pleural pressure (Ppl) assists left ventricular (LV) ejection, we compared the effects of phasic systolic or diastolic increases in Ppl (40-60 mmHg) with use of an isolated canine heart-lung preparation with constant venous return. Positive Ppl during systole (S) caused left atrial transmural pressure (Platm = Pla - Ppl) to decrease by 1.25 +/- 0.46 (SE) mmHg (P less than 0.025). Central blood volume (CBV), the volume of blood in the heart, lungs, and thoracic great vessels, decreased by 29 +/- 4.0 (SE) ml (P less than 0.001). When Ppl was raised for an equal duration during diastole (D), the decrease in Platm was not significant, but there was a significant decrease in CBV (10.5 +/- 4.1 ml, P less than 0.05). With constant venous return, these changes suggested that phasic elevations in Ppl in either S or D assisted LV ejection by decreasing LV afterload. To test the hypothesis that positive Ppl during D reduced afterload by emptying the thoracic aorta, we compared the effects of diastolic positive Ppl with a rigid aorta vs. a compliant aorta. Although there was no statistical difference in the effects of diastolic positive Ppl on Platm, the decrease in CBV was significantly greater when the aorta was compliant than when it was rigid (23 +/- 2.2 vs. 17 +/- 2.7 ml, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of systolic and diastolic positive pleural pressure pulses with altered cardiac contractility.

Positive pleural pressure (Ppl) decreases left ventricular afterload and preload. The resulting change in cardiac output (CO) in response to these altered loading conditions varies with the baseline level of cardiac contractility. In an isolated canine heart-lung preparation, we studied the effects of positive Ppl applied phasically during systole or diastole on CO and on the cardiac function curve (the relationship between CO and left atrial transmural pressure). When baseline cardiac contractility was enhanced by epinephrine infusion, systolic and diastolic positive Ppl decreased CO equally (1,931 +/- 131 to 1,419 +/- 124 and 1,970 +/- 139 to 1,468 +/- 139 ml/min, P less than 0.01) and decreased the pressure gradient driving venous return. However, neither shifted the position of the cardiac function curve, suggesting that the predominant effect of positive Ppl was decreased preload. When baseline cardiac contractility was depressed by severe respiratory acidosis, diastolic positive Ppl pulses caused no significant change in CO (418 +/- 66 to 386 +/- 52 ml/min), the cardiac function curve, or the pressure gradient for venous return. However, systolic positive Ppl pulses increased CO from 415 +/- 70 to 483 +/- 65 ml/min (P less than 0.01) and significantly shifted the cardiac function curve to the left. Thus the effect of Ppl pulsations on CO works through different mechanisms, depending on the state of cardiac contractility.

Locus of hypoxic vasoconstriction in isolated ferret lungs.

To determine whether hypoxic pulmonary vasoconstriction (HPV) occurs mainly in alveolar or extra-alveolar vessels in ferrets, we used two groups of isolated lungs perfused with autologous blood and a constant left atrial pressure (-5 Torr). In the first group, flow (Q) was held constant at 50, 100, and 150 ml.kg-1 X min-1, and changes in pulmonary arterial pressure (Ppa) were recorded as alveolar pressure (Palv) was lowered from 25 to 0 Torr during control [inspired partial pressure of O2 (PIO2) = 200 Torr] and hypoxic (PIO2 = 25 Torr) conditions. From these data, pressure-flow relationships were constructed at several levels of Palv. In the control state, lung inflation did not affect the slope of the pressure-flow relationships (delta Ppa/delta Q), but caused the extrapolated pressure-axis intercept (Ppa0), representing the mean backpressure to flow, to increase when Palv was greater than or equal to 5 Torr. Hypoxia increased delta Ppa/delta Q and Ppa0 at all levels of Palv. In contrast to its effects under control condition, lung inflation during hypoxia caused a progressive decrease in delta Ppa/delta Q, and did not alter Ppa0 until Palv was greater than or equal to 10 Torr. In the second group of experiments flow was maintained at 100 ml.kg-1 X min-1, and changes in lung blood volume (LBV) were recorded as Palv was varied between 20 and 0 Torr. In the control state, inflation increased LBV over the entire range of Palv. In the hypoxic state inflation decreased LBV until Palv reached 8 Torr; at Palv 8-20 Torr, inflation increased LBV.(ABSTRACT TRUNCATED AT 250 WORDS)

Longitudinal distribution of vascular compliance in the canine lung.

With an isolated perfused canine lung, the compliance of pulmonary circulation was measured and partitioned into components corresponding to alveolar and extra-alveolar compartments. When the lungs were in zone 3, changes in outflow pressure (delta Po) affected all portions of the vasculature causing a change in lung blood volume (delta V). Thus the ratio delta V/delta Po in zone 3 represented the compliance of the entire pulmonary circulation (Cp) plus that of the left atrium (Cla). When the lungs were in zone 2, changes in Po affected only the extra-alveolar vessels that were downstream from the site of critical closure in the alveolar vessels. Thus the ratio delta V/delta Po with forward flow in zone 2 represented the compliance of the venous extra-alveolar vessels (Cv) plus Cla. With reverse flow in zone 2, delta V/delta Po represented the compliance of the arterial extra-alveolar vessels (Ca). The compliance of the alveolar compartment (Calv) was calculated from the difference between Cp and the sum of Ca + Cv. When Po was 6-11 mmHg, Cp was 0.393 +/- 0.0380 (SE) ml X mmHg-1 X kg-1 with forward perfusion and 0.263 +/- 0.0206 (SE) ml X mmHg-1 X kg-1 with reverse perfusion. Calv was 79 and 68% of Cp with forward and reverse perfusion, respectively. When Po was raised to 16-21 mmHg, Cp decreased to 0.225 +/- 0.0235 (SE) ml X mmHg-1 X kg-1 and 0.183 +/- 0.0133 (SE) ml X mmHg-1 X kg-1 with forward and reverse perfusion, respectively. Calv also decreased but remained the largest contributor to Cp. We conclude that the major site of pulmonary vascular compliance in the canine lung is the alveolar compartment, with minor contributions from the arterial and venous extra-alveolar segments.

Effects of hyperinflation and CPAP on work of breathing and respiratory failure in dogs.

Increased end-expiratory lung volume (EELV) and airway resistance are both characteristic features of obstructive lung disease. Increased EELV alone loads the respiratory muscles and may cause respiratory failure, changes that could be reversed by continuous positive airway pressure (CPAP). To study the effects of elevated EELV on respiration without increased airway resistance, we used a mechanical analogue of airway closure to increase EELV in six spontaneously breathing anesthetized dogs. Hyperinflation of 0.84 +/- 0.11 liter for 30 min decreased minute ventilation from 4.8 +/- 0.37 to 3.5 +/- 0.21 l/min and increased arterial PCO2 from 40.3 +/- 1.5 to 73.2 +/- 8.1 Torr (both P < 0.01). Inspiratory work per breath increased 3-fold, work per liter increased 3.7-fold, and work per minute increased 2.8-fold (all P < 0.01). CPAP at 15 cmH2O restored minute ventilation to 4.3 +/- 0.3 l/min and reduced arterial PCO2 to 54 +/- 6.6 Torr (NS vs. baseline). All measurements of inspiratory work were also restored to baseline, but cardiac output was reduced (baseline 3.09 +/- 0.36, hyperinflation 2.71 +/- 0.36, hyperinflation + CPAP 1.94 +/- 0.29 l/min; P < 0.05, baseline vs. hyperinflation + CPAP). We conclude that increases in EELV mimic important features of airway obstruction, increase inspiratory work, and can cause respiratory failure independent of increased airway resistance. This respiratory failure is reversed by CPAP at the potential expense of hemodynamic compromise.

Spontaneous injury in isolated sheep lungs: role of perfusate leukocytes and platelets.

Perfusion of isolated sheep lungs with blood causes spontaneous edema and hypertension preceded by decreases in perfusate concentrations of leukocytes (WBC) and platelets (PLT). To determine whether these decreases were caused by pulmonary sequestration, we continuously measured blood flow and collected pulmonary arterial and left atrial blood for cell concentration measurements in six lungs early in perfusion. Significant sequestration occurred in the lung, but not in the extracorporeal circuit. To determine the contribution of these cells to spontaneous injury in this model, lungs perfused in situ with a constant flow (100 ml.kg-1.min-1) of homologous leukopenic (WBC = 540 mm-3, n = 8) or thrombocytopenic blood (PLT = 10,000 mm-3, n = 6) were compared with control lungs perfused with untreated homologous blood (WBC = 5,320, PLT = 422,000, n = 8). Perfusion of control lungs caused a rapid fall in WBC and PLT followed by transient increases in pulmonary arterial pressure, lung lymph flow, and perfusate concentrations of 6-ketoprostaglandin F1 alpha and thromboxane B2. The negative value of reservoir weight (delta W) was measured as an index of fluid entry into the lung extravascular space during perfusion. delta W increased rapidly for 60 min and then more gradually to 242 g at 180 min. This was accompanied by a rise in the lymph-to-plasma oncotic pressure ratio (pi L/pi P). Relative to control, leukopenic perfusion decreased the ratio of wet weight to dry weight, the intra- plus extravascular blood weight, and the incidence of bloody lymph. Thrombocytopenic perfusion increased lung lymph flow and the rate of delta W, decreased pi L/pi P and perfusate thromboxane B2, and delayed the peak pulmonary arterial pressure. These results suggest that perfusate leukocytes sequestered in the lung and contributed to hemorrhage but were not necessary for hypertension and edema. Platelets were an important source of thromboxane but protected against edema by an unknown mechanism.

Influence of diffusion on estimations of protein reflection coefficient by double-indicator method.

In isolated perfused organs, vascular protein reflection coefficients (sigma) can be calculated from the changes in hematocrit and perfusate protein concentration (CP) that occur during edema formation. This technique requires the assumption that transvascular protein flux by diffusion is negligible. To assess diffusion-induced errors in calculations of sigma, we derived an expression for CP that includes determinants of diffusive protein flux: protein permeability-surface area product (PS), transvascular fluid flux (J), true sigma, and transvascular protein concentration. We used this expression to obtain values of CP under various experimental conditions and then calculated values of sigma (measured sigma) for those conditions. Diffusion causes measured sigma to be lower than true sigma. The diffusion-induced error is larger and potentially substantial when J/PS is low and when true sigma is high. Diffusion-induced error is also larger when the amount of edema formation is greater. In recent isolated canine lung experiments where J/PS was approximately 2.7, diffusion-induced errors in measured sigma for albumin would have been approximately 0.06 (at true sigma = 0.5) and approximately 0.18 (at true sigma = 0.9). When J/PS was higher, the potential for diffusion-induced errors was much smaller. We conclude that diffusion causes underestimation of true sigma and that the error in measured sigma may be substantial when J/PS is < 5 and when true sigma is > 0.5.

Modulation of maximal inspiratory airflow by neuromuscular activity: effect of CO2.

To determine how maximal inspiratory airflow (VImax) is modulated by changes in airway neuromuscular activity, we analyzed pressure-flow relationships obtained during inspiration and expiration in isolated upper airways of anesthetized hyperoxic dogs at different levels of CO2. Inspiratory airflow (VI), hypopharyngeal pressure (Php), pharyngeal pressure at the flow-limiting site (FLS), and alae nasi (AN) and genioglossus (GG) electromyographic (EMG) activity were recorded while VI limitation was produced by rapidly lowering Php until VI plateaued at VImax. VImax and its mechanical determinants, pharyngeal critical pressure (Pcrit) and nasal resistance (Rn) upstream to the FLS, were measured. During hypercapnia (high CO2), VImax increased significantly during inspiration (217.3) and expiration (184.1%). These increases were associated with significant increases in phasic but not tonic AN and GG activity. They were also associated with decreases in Pcrit from -6.2 +/- 1.6 (SE) at hypocapnia to -9.3 +/- 3.0 and -11.8 +/- 3.4 cmH2O at high CO2 during expiration and inspiration, respectively. No significant changes in Rn occurred. When phasic neuromuscular activity was abolished by complete neuromuscular blockade in three dogs, these increases in VImax and decreases in Pcrit at high CO2 were eliminated. When phasic EMG activity was accentuated in four vagotomized dogs, significant increases in VImax and decreases in Pcrit were demonstrated during inspiration vs. expiration at high CO2. These findings indicate that upper airway neuromuscular activity increases VImax in the isolated upper airway by decreasing collapsibility (Pcrit) at the FLS site when neuromuscular activity is stimulated by hypercapnia.

Mechanical ventilation in acute lung injury and acute respiratory distress syndrome.

Mechanical ventilation provides life-sustaining support for most patients with acute lung injury and acute respiratory distress syndrome; however, traditional approaches to mechanical ventilation may cause ventilator-associated lung injury, which could exacerbate or perpetuate respiratory failure caused initially by conditions such as pneumonia, sepsis, and trauma. This article reviews the theory, laboratory data, and results of recent clinical trials that suggest that modified ventilator strategies can reduce ventilator-associated lung injury and improve clinical outcomes.

Effects of positive end-expiratory pressure on the canine venous return curve.

To study the mechanism whereby positive end-expiratory pressure (PEEP) decreases venous return, we used a closed-chest canine venous bypass preparation to study the effects of 10 mm Hg PEEP on the systemic venous pressure-flow curves from the superior and inferior vena cava (SVC and IVC). These curves were characterized by three variables: the critical downstream pressure below which venous return was maximal (PCRIT), the conductance to venous return (GVR), and the effective upstream pressure driving venous return. PEEP reduced venous return by decreasing the maximal venous return even when the pressures at the outflow of the IVC and SVC were maintained below zero. PEEP increased PCRIT in the SVC and IVC (SVC: -0.31 +/- 0.53 to 3.21 +/- 0.84; IVC: -0.41 +/- 0.64 to 5.23 +/- 1.02 (SE) mm Hg; p less than 0.005). GVR in the SVC was reduced (52.5 +/- 26 to 37.8 +/- 5.3 (SE) ml/min/mm Hg; p less than 0.005), but changes in the IVC did not reach statistical significance. These changes were partially offset by increases in the upstream pressure driving venous return (SVC: 9.44 +/- 0.54 to 12.25 +/- 0.71; IVC: 9.42 +/- 0.69 to 12.51 +/- 1.02 (SE) mm Hg; p less than 0.01). Analysis of these findings suggests that PEEP may alter venous return through effects on the peripheral circulation, independent of its effects on the heart.

Positive pleural pressure decreases coronary perfusion.

Pressure surrounding the heart (PSH) rises with maneuvers that increase pleural pressure. This may decrease left ventricular (LV) oxygen demand by reducing LV afterload. However, positive PSH may also directly impede coronary flow. To study the effects of positive PSH on coronary perfusion, PSH was increased in 10-mmHg increments from 0 to 60 mmHg in an isolated canine heart-lung preparation with constant venous return, arterial pressure, and lung volume. Increased PSH caused a rapid significant (P less than 0.001) fall in left atrial transmural pressure (PLATM) of up to 1.28 +/- 0.31 mmHg. With constant venous return and lung volume, this was interpreted to reflect decreased LV afterload. However, at levels of PSH greater than 30 mmHg, initial decreases in PLATM were followed by sustained increases, suggesting that there was a deterioration in cardiac function despite the lower level of afterload. Increased PSH was also associated with decreases in circumflex coronary artery flow [flow (ml/min) = 52.4 - 0.4PSH, P less than 0.01]. Moreover, when the circumflex coronary artery was maximally dilated with adenosine, the effects of PSH were amplified [flow (ml/min) = 137.9 - 1.78PSH, P less than 0.001], indicating that positive PSH mechanically impeded coronary flow. When PSH was raised to 60 mmHg for 90 s, the aortic-coronary sinus lactate concentration difference fell from 0.71 +/- 0.09 to 0.10 +/- 0.21 mM (mean +/- SE, P less than 0.001, n = 8), suggesting myocardial ischemia. We conclude that positive PSH directly decreases myocardial perfusion. This may lead to ischemic cardiac dysfunction, especially in patients with low arterial pressure or coronary artery disease.

Effects of positive end-expiratory pressure on the gradient for venous return.

The major mechanism whereby positive end-expiratory pressure (PEEP) decreases cardiac output is believed to be a decrease in the pressure gradient for venous return. However, although PEEP increases right atrial pressure (PRA), It may also elevate mean systemic pressure (PMS), the static circulatory filling pressure that is the upstream pressure for venous return. In an intact canine preparation, we studied the effects of 15 cm H2O PEEP on cardiac output, PRA, and PMS (the equilibrium PRA during ventricular fibrillation). To examine the role of neurovascular reflexes, PEEP was applied before and after either carotid sinus and vagal denervation (CSV) or total spinal anesthesia with arterial pressure restored by epinephrine infusion (SAE). To examine the effects of PEEP-induced elevations of abdominal pressure, the abdomen was bound or widely opened and the abdominal contents exteriorized. With reflexes intact, neither binding nor opening the abdomen altered the rise in PMS during PEEP. CSV attenuated the rise in Pms by 17% (Control, 4.89 +/- 0.3 SE; CSV, 4.04 +/- 0.22 mmHg; p less than 0.01), and SAE attenuated it by 49% (Control, 4.21 +/- 0.27; SAE, 2.14 +/- 0.31 mmHg; p less than 0.00005). After either CSV or SAE, the rise in Pms was not affected by binding. PEEP decreased (Pms-PRA) only when the abdomen was bound because of a greater rise in PRA, or during SAE because of a lesser rise in Pms. Under control conditions, PEEP increased Pms and PRA equally [(PRA-Pms) = 3.89 +/- 0.26 without PEEP versus 4.13 +/- 0.29 mm Hg with PEEP]. We conclude that PEEP increases Pms by both reflex and mechanical means independent of increased abdominal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Biologic variability in mechanical ventilation rate and tidal volume does not improve oxygenation or lung mechanics in canine oleic acid lung injury.

Mechanical ventilation in patients with acute respiratory distress syndrome and acute lung injury (ALI) remains a difficult challenge because of the conflict between maintaining adequate gas exchange and furthering lung injury via overdistention. In a recent study, Lefevre and colleagues (Am. J. Respir. Crit. Care Med. 1996;154: 1567-1572) suggested that mechanical ventilation with natural biologic variability (BV) in breath-to-breath respiratory frequency (f) and VT could reduce lung injury and improve gas exchange without increases in mean airway pressure (Paw) or peak inspiratory pressure (PIP). However, significant differences in cardiac output (CO), Pa(CO(2)), pH, and delivered VT between the treatment groups in their study could have influenced these results. Because of the potential implications of these findings for patient care, we attempted to confirm these findings by Lefevre and colleagues in a canine model of oleic acid-induced lung injury. Eighteen mongrel dogs were anesthetized in the supine position, paralyzed, and mechanically ventilated with 50% O(2) at f = 15 breaths/min, and VT was adjusted to achieve an end-tidal CO(2) of 30 to 35 mm Hg. Lung injury was produced by infusion of 0.06 ml/kg oleic acid solution into the right atrium over a 30-min period. Animals were then randomized to either conventional ventilation at the baseline settings (n = 9) or to BV at the same mean VT and f (n = 9). Both groups received comparable degrees of injury, and hemodynamic and ventilatory parameters were closely matched, with no differences in mean VT, PIP, mean Paw, Pa(CO(2)), pH, CO, pulmonary artery occlusion pressure, or arterial pressure (Pa). However, no differences between the two groups were found in Pa(O(2)), shunt, or static compliance over a 4-h period. When hemodynamic and ventilatory parameters were well matched in a canine model of ALI, BV showed no advantage over conventional ventilation at constant VT and f.

Effects of positive end-expiratory pressure and body position on pressure in the thoracic great veins.

Positive end-expiratory pressure (PEEP) commonly decreases cardiac output. The major cause of this is believed to be decreased venous return due to increased right atrial pressure. We hypothesized that when the lungs were hyperinflated they could also restrict venous return by directly compressing the thoracic vena cavae. We measured the longitudinal distribution of pressure in the thoracic vena cavae of 10 dogs on and off 10 mm Hg PEEP, in the supine (S), prone (P), right lateral (RL), and left lateral decubitus (LL) positions. In the superior vena cava (SVC) both on and off PEEP, and in the inferior vena cava (IVC) off PEEP, pressure fell uniformly from the thoracic inlet to the right atrium. However, in the IVC on PEEP, intravascular pressure fell abruptly by up to 5 mm Hg. This pressure drop occurred in a discrete (1 to 2-cm) segment of the IVC, suggesting a localized increased in extravascular surface pressure. When this pressure inflection was present, changes in right atrial pressure had no effect on pressure in the IVC upstream of the inflection, consistent with a "vascular waterfall." These observations were most prominent in the LL, least common in the RL, and variably present in the P and S positions. Occlusion of the right bronchus intermedius prior to PEEP (preventing right lower, middle, and accessory lobe inflation) prevented the appearance of the pressure inflection during PEEP in the LL but not in the S or P positions. We conclude that PEEP impedes venous return partly by direct compression of the IVC, predominantly in positions in which the IVC is non-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of lung inflation on blood flow during cardiopulmonary resuscitation in the canine isolated heart-lung preparation.

Using an isolated, fibrillated canine heart-lung preparation, we studied the effects of simultaneous lung inflation and chest compression on blood flow in a model of cardiopulmonary resuscitation. The heart and lungs were placed in an artificial thorax with the great vessels and trachea exteriorized and attached to an artificial perfusion circuit and respirator, respectively. The blood volume of the system was adjusted to obtain various levels of static equilibrium pressure. Blood flow was obtained by cyclically raising and lowering the pressure in the artificial thorax, simulating the changes in pleural pressure that occur during cardiopulmonary resuscitation. Lung inflation during the compression phase caused an increase in cardiopulmonary resuscitation blood flow when the change in pleural pressure was small and when static equilibrium pressure was high. In contrast, lung inflation caused a decrease in blood flow when changes in pleural pressure were high and when blood volume was low. These results suggest that the driving pressure for blood flow during chest compression may be increased by lung inflation when the pulmonary blood vessels are filled with blood. However, blood may become trapped in the right heart and unavailable for transfer to the periphery during chest compression if lung inflation causes the alveolar blood vessels to collapse.