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.     

High-frequency oscillatory ventilation increases canine pulmonary epithelial permeability

To investigate the effect of high-frequency oscillatory ventilation (HFOV) on the pulmonary epithelial permeability, we measured the clearance rate of nebulized sodium pertechnetate (99mTcO4-) and diethylenetriaminepentaacetate (99mTc-DTPA) before and after a 4-h period of mechanical ventilation in anesthetized mongrel dogs. The animals also underwent experiments with 4 h of spontaneous breathing (SB) and intermittent positive-pressure ventilation (IPPV) with and without addition of positive end-expiratory pressure (PEEP) for comparison. After IPPV and SB there was no change in the clearance rate of either 99mTcO4- or 99mTc-DTPA. After IPPV + PEEP and HPOV (8 and 16 Hz), there was an increase in the clearance rate of 99mTc-DTPA, but an increase in clearance rate of 99mTcO4- was seen after IPPV + PEEP only. In a separate group of dogs an increase in end-tidal lung volume was demonstrated after 4 h of ventilation with IPPV + PEEP (but not after HFOV), and this may account for the measured increase in 99mTcO4- clearance. We conclude that an increase in 99mTc-DTPA clearance rate after HFOV signifies an increase in pulmonary epithelial permeability, possibly through the mechanism of damage to the intercellular junctions during HFOV.     

PEEP inhibits hypoxic pulmonary vasoconstriction in dogs

The effects of an increase in alveolar pressure on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We therefore studied the effects of positive end-expiratory pressure (PEEP) on pulmonary hemodynamics in 13 pentobarbital-anesthetized dogs ventilated alternately in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). In this intact animal model, HPV was defined as the gradient between hypoxic and hyperoxic transmural (tm) mean pulmonary arterial pressure [Ppa(tm)] at any level of cardiac index (Q). Ppa(tm)/Q plots were constructed with mean transmural left atrial pressure [Pla(tm)] kept constant at approximately 6 mmHg (n = 5 dogs), and Ppa(tm)/PEEP plots were constructed with Q kept constant approximately 2.8 l.min-1.m-2 and Pla(tm) kept constant approximately 8 mmHg (n = 8 dogs). Q was manipulated using a femoral arteriovenous bypass and a balloon catheter in the inferior vena cava. Pla(tm) was held constant by a balloon catheter placed by left thoracotomy in the left atrium. Increasing PEEP, from 0 to 12 Torr by 2-Torr increments, at constant Q and Pla(tm), increased Ppa(tm) from 14 +/- 1 (SE) to 19 +/- 1 mmHg in hyperoxia but did not affect Ppa(tm) (from 22 +/- 2 to 23 +/- 1 mmHg) in hypoxia. Both hypoxia and PEEP, at constant Pla(tm), increased Ppa(tm) over the whole range of Q studied, from 1 to 5 l/min, but more at the highest than at the lowest Q and without change in extrapolated pressure intercepts. Adding PEEP to hypoxia did not affect Ppa(tm) at all levels of Q.(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.     

Hemodynamic basis for cocaine-induced pulmonary edema in dogs.

We tested the hypothesis that cocaine-induced impairment of left ventricular function results in cardiogenic pulmonary edema. Mongrel dogs, anesthetized with alpha-chloralose, were injected with two doses of cocaine (5 mg/kg iv) 27 min apart. Cocaine produced transient decreases in aortic and left ventricular systolic pressures that were followed by increases exceeding control. As aortic pressure recovered, left ventricular end-diastolic, left atrial (Pla), pulmonary arterial (Ppa), and central venous pressures rose. Cardiac output and stroke volume were reduced when measured 4-5 min after cocaine administration. Peak Ppa and Pla were 31 +/- 5 (SE) mmHg (range 17-51 mmHg) and 26 +/- 5 mmHg (range 12-47 mmHg), respectively. Increases in extravascular lung water content (4.10 to 6.24 g H2O/g dry lung wt) developed in four animals in which Pla exceeded 30 mmHg. Analysis of left ventricular function curves revealed that cocaine depressed the inotropic state of the left ventricle. Cocaine-induced changes in hemodynamics spontaneously recovered and could be elicited again by the second dose of the drug. Our results show that cocaine-induced pulmonary hypertension, associated with decreased left ventricular function, produces pulmonary edema if pulmonary vascular pressures rise sufficiently.     

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.     

Effects of positive end-expiratory pressure on hepatic blood flow and performance

Positive end-expiratory pressure (PEEP) may impair extrapulmonary organ function. However, the effects of PEEP on the liver are unclear. We tested the hypothesis that at a constant cardiac output (CO), PEEP does not induce changes in hepatic blood flow (QL) and parenchymal performance. In splenectomized, close-chested canine preparations (group I, n = 6), QL was derived as hepatic outflow using electromagnetic flow probes (QLemf), and hepatic performance was defined by extraction and clearance of indocyanine green (ICG). In a noninvasive model (group II, n = 7), the effects of PEEP on hepatic performance alone were similarly analyzed. Measurements were taken during intermittent positive-pressure ventilation (IPPV1), after addition of 10 cmH2O PEEP to IPPV (PEEP1), during continued PEEP but after return of CO to IPPV1 levels by intravascular volume infusions (PEEP2), and after removal of both PEEP and excess blood volume (IPPV2). Phasic inspiratory decreases in QLemf present during positive-pressure ventilation were not increased during either PEEP1 or PEEP2. Mean QLemf decreased proportionately with CO during PEEP1 (P less than 0.05), but was restored to IPPV1 levels in a parallel fashion with CO during PEEP2. The ICG pharmacokinetic responses to PEEP were complex, with differential effects on extraction and clearance. Despite this, hepatic performance was not imparied in either group. we conclude that global QL reductions during PEEP are proportional to PEEP-induced decreases in CO and are preventable by returning CO to pre-PEEP levels by intravascular volume infusions. However, covarying changes in blood volume and hepatic outflow resistance may independently modulate hepatic function.     

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.     

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 left atrial pressure on bronchial vascular hemodynamics

We studied the bronchial vascular response to downstream pressure elevation by increasing left atrial pressure (Pla) and mean airway pressure (Paw) with positive end-expiratory pressure (PEEP). In seven pentobarbital-anesthetized ventilated sheep, we cannulated and perfused the bronchial branch of the bronchoesophageal artery. Steady-state bronchial artery pressure- (Pba) flow (Qba) relationships were obtained as Pla was increased by inflating a balloon catheter in the left atrium. Bronchial vascular resistance (BVR), determined by the inverse slope of the Pba-Qba relationship, increased significantly from 3.2 +/- 0.3 (SE) mmHg.ml-1.min-1 at a Pla of 2.9 +/- 0.7 mmHg to 5.1 +/- 0.5 mmHg.ml-1.min-1 at a Pla of 20.1 +/- 2.0 mmHg (P = 0.0007). Under control Qba (23.3 +/- 1.2 ml/min), these changes in BVR represent a 3.6 +/- 0.7-mmHg increase in Pba per mmHg increase in Pla. The zero-flow pressure increased 1.3 +/- 0.2 mmHg/mmHg increase in Pla. After infusion of papaverine, a smooth muscle paralytic agent, directly into the bronchial artery, BVR decreased significantly to 1.3 +/- 0.7 mmHg.ml-1.min-1 (P = 0.0004). Under these dilated conditions, BVR was unaltered by increases in Pla. After papaverine administration, Pba increased 0.9 +/- 0.1 and 1.2 +/- 0.1 mmHg/mmHg increase in Pla during control and zero-flow conditions, respectively. Thus the effect of Pla elevation on BVR appears to be dependent on active smooth muscle responses. Paw elevation had similar effects on Pba. Under control Qba, Pba increased 2.2 +/- 0.4 mmHg/mmHg increase in Paw.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of high-frequency jet ventilation on arterial baroreflex regulation of heart rate

Fifteen anesthetized mechanically ventilated patients recovering from multiple trauma were studied to compare the effects of high-frequency jet ventilation (HFJV) and continuous positive-pressure ventilation (CPPV) on arterial baroreflex regulation of heart rate. Systolic arterial pressure and right atrial pressure were measured using indwelling catheters. Electrocardiogram (ECG) and mean airway pressure were continuously monitored. Lung volumes were measured using two linear differential transformers mounted on thoracic and abdominal belts. Baroreflex testing was performed by sequential intravenous bolus injections of phenylephrine (200 micrograms) and nitroglycerin (200 micrograms) to raise or lower systolic arterial pressure by 20-30 Torr. Baroreflex regulation of heart rate was expressed as the slope of the regression line between R-R interval of the ECG and systolic arterial pressure. In each mode of ventilation the ventilatory settings were chosen to control mean airway pressure and arterial PCO2 (PaCO2). In HFJV a tidal volume of 159 +/- 61 ml was administered at a frequency of 320 +/- 104 breaths/min, whereas in CPPV a tidal volume of 702 +/- 201 ml was administered at a frequency of 13 +/- 2 breaths/min. Control values of systolic arterial pressure, R-R interval, mean pulmonary volume above apneic functional residual capacity, end-expiratory pulmonary volume, right atrial pressure, mean airway pressure, PaCO2, pH, PaO2, and temperature before injection of phenylephrine or nitroglycerin were comparable in HFJV and CPPV. Baroreflex regulation of heart rate after nitroglycerin injection was significantly higher in HFJV (4.1 +/- 2.8 ms/Torr) than in CPPV (1.96 +/- 1.23 ms/Torr).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of systemic venous pressure elevation on lymph flow and lung edema formation

Pulmonary lymph drains into the thoracic duct and then into the systemic venous circulation. Since systemic venous pressure (SVP) must be overcome before pulmonary lymph can flow, variations in SVP may affect lymph flow rate and therefore the rate of fluid accumulation within the lung. The importance of this issue is evident when one considers the variety of clinical interventions that increase SVP and promote pulmonary edema formation, such as volume infusion, positive-pressure ventilation, and various vasoactive drug therapies. We recorded pulmonary arterial pressure (PAP), left atrial pressure (LAP), and SVP in chronic unanesthetized sheep. Occlusion balloons were placed in the left atrium and superior vena cava to control their respective pressures. The superior vena caval occluder was placed above the azygos vein so that bronchial venous pressure would not be elevated when the balloon was inflated. Three-hour experiments were carried out at various LAP levels with and without SVP being elevated to 20 mmHg. The amount of fluid present in the lung was determined by the wet-to-dry weight ratio method. At control LAP levels, no significant difference in lung fluid accumulation could be shown between animals with control and elevated SVP levels. When LAP was elevated above control a significantly greater amount of pulmonary fluid accumulated in animals with elevated SVP levels compared with those with control SVP levels. We conclude that significant excess pulmonary edema formation will occur when SVP is elevated at pulmonary microvascular pressures not normally associated with rapid fluid accumulation.     

Responses of pulmonary C-fibre and rapidly adapting receptor afferents to pulmonary congestion and edema in dogs.

The effects of cardiogenic and noncardiogenic pulmonary edema on the activities of rapidly adapting receptors (RARs) and pulmonary C-fibre receptors were investigated in dogs anaesthetized with chloralose. Cardiogenic pulmonary edema was produced by elevating the mean left atrial pressure by 25 mmHg (1 mmHg = 133.32 Pa) above the control value for a period of 45 min, by partial obstruction of the mitral valve. Noncardiogenic pulmonary edema was produced by injecting alloxan (100 mg/kg) intravenously. The effect of the latter was examined on RARs alone. Cardiogenic edema activated RARs (n = 8) and the activity was greatest during the first few minutes after elevation of mean left atrial pressure. The pulmonary C-fibre receptors (n = 6) were also activated by cardiogenic edema, but these responses were variable. Noncardiogenic pulmonary edema also activated RAR (n = 6), and this response was maintained during the entire recording period (20 min). The extravascular lung water (%), measured 15 min (n = 5) and 45 min (n = 5) after the elevation of the mean left atrial pressure, was significantly elevated above control values. However, these two values were not significantly different from each other. The extravascular lung water increased significantly after the injection of alloxan also (n = 5). These results show that during pulmonary edema, there is significant stimulation of the RARs and the pulmonary C-fibre receptors. It is suggested that the reflex respiratory responses observed in pulmonary edema may be due to the activation of both the RARs and the pulmonary C-fibre receptors.     

Effect of thoracic duct drainage on hydrostatic pulmonary edema and pleural effusion in sheep

Positive end-expiratory pressure (PEEP) increases central venous pressure, which in turn impedes return of systemic and pulmonary lymph, thereby favoring formation of pulmonary edema with increased microvascular pressure. In these experiments we examined the effect of thoracic duct drainage on pulmonary edema and hydrothorax associated with PEEP and increased left atrial pressure in unanesthetized sheep. The sheep were connected via a tracheostomy to a ventilator that supplied 20 Torr PEEP. By inflation of a previously inserted intracardiac balloon, left atrial pressure was increased to 35 mmHg for 3 h. Pulmonary arterial, systemic arterial, and central venous pressure as well as thoracic duct lymph flow rate were continuously monitored, and the findings were compared with those in sheep without thoracic duct cannulation (controls). At the end of the experiment we determined the severity of pulmonary edema and the volume of pleural effusion. With PEEP and left atrial balloon insufflation, central venous and pulmonary arterial pressure were increased approximately threefold (P less than 0.05). In sheep with a thoracic duct fistula, pulmonary edema was less (extra-vascular fluid-to-blood-free dry weight ratio 4.8 +/- 1.0 vs. 6.1 +/- 1.0; P less than 0.05), and the volume of pleural effusion was reduced (2.0 +/- 2.9 vs. 11.3 +/- 9.6 ml; P less than 0.05). Our data signify that, in the presence of increased pulmonary microvascular pressure and PEEP, thoracic duct drainage reduces pulmonary edema and hydrothorax.     

Effects of pulmonary vascular pressures and flow on airway and parenchymal mechanics in isolated rat lungs.

Changes in pulmonary hemodynamics have been shown to alter the mechanical properties of the lungs, but the exact mechanisms are not clear. We therefore investigated the effects of alterations in pulmonary vascular pressure and flow (Q(p)) on the mechanical properties of the airways and the parenchyma by varying these parameters independently in three groups of isolated perfused normal rat lungs. The pulmonary capillary pressure (Pc(est)), estimated from the pulmonary arterial (Ppa) and left atrial pressure (Pla), was increased at constant Q(p) (n = 7), or Q(p) was changed at Pc(est) = 10 mmHg (n = 7) and at Pc(est) = 20 mmHg (n = 6). In each condition, the airway resistance (Raw) and parenchymal damping (G) and elastance (H) were identified from the low-frequency pulmonary input impedance spectra. The results of measurements made under isogravimetric conditions were analyzed. The changes observed in the mechanical parameters were consistent with an altered Pla: monotonous increases in Raw were observed with increasing Pla, whereas G and H were minimal at Pla of approximately 7-10 mmHg and increased at lower and higher Pla. The results indicate that Pla, and not Ppa or Q(p), is the primary determinant of the mechanical condition of the lungs after acute changes in pulmonary hemodynamics: the parenchymal mechanics are impaired if Pla is lower or higher than physiological, whereas airway narrowing occurs at high Pla.     

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.     

Hemodynamic effects of synchronous high-frequency jet ventilation in mitral regurgitation

We tested the hypothesis that increases in intrathoracic pressure (ITP), by decreasing the pressure gradient for anterograde left ventricular (LV) ejection, should augment cardiac output in acute mitral regurgitation (MR). In a pentobarbital-anesthetized closed-chest canine model, LV stroke volume (SLLV) was measured by integration from an aortic flow probe signal. MR was induced by a regurgitant ring. ITP was elevated over apnea by means of intermittent positive-pressure ventilation (IPPV), asynchronous (asynch) high-frequency jet ventilation (HFJV), and cardiac cycle-specific (synch) HFJV. IPPV resulted in the greatest increase in ITP. MR caused a fall in SVLV and a rise in LV filling pressure that were not altered by IPPV. Compared with IPPV or apnea, both asynch and synch HFJV increased SVLV and reduced LV filling pressures (P less than 0.05). Systolic synch HFJV induced a greater increase in SVLV (32%) than diastolic synch HFJV (26%) despite similar ventilatory settings. Our data suggest that when LV contractility is normal but MR impairs forward flow, cardiac cycle-specific increases in ITP will augment forward flow.     

Hypoxic pulmonary vasoconstriction does not affect hydrostatic pulmonary edema formation

We studied the effects of regional hypoxic pulmonary vasoconstriction (HPV) on lobar flow diversion in the presence of hydrostatic pulmonary edema. Ten anesthetized dogs with the left lower lobe (LLL) suspended in a net for continuous weighing were ventilated with a bronchial divider so the LLL could be ventilated with either 100% O2 or a hypoxic gas mixture (90% N2-5% CO2-5% O2). A balloon was inflated in the left atrium until hydrostatic pulmonary edema occurred, as evidenced by a continuous increase in LLL weight. Left lower lobe flow (QLLL) was measured by electromagnetic flow meter and cardiac output (QT) by thermal dilution. At a left atrial pressure of 30 +/- 5 mmHg, ventilation of the LLL with the hypoxic gas mixture caused QLLL/QT to decrease from 17 +/- 4 to 11 +/- 3% (P less than 0.05), pulmonary arterial pressure to increase from 35 +/- 5 to 37 +/- 6 mmHg (P less than 0.05), and no significant change in rate of LLL weight gain. Gravimetric confirmation of our results was provided by experiments in four animals where the LLL was ventilated with an hypoxic gas mixture for 2 h while the right lung was ventilated with 100% O2. In these animals there was no difference in bloodless lung water between the LLL and right lower lobe. We conclude that in the presence of left atrial pressures high enough to cause hydrostatic pulmonary edema, HPV causes significant flow diversion from an hypoxic lobe but the decrease in flow does not affect edema formation.     

Effects of high-frequency oscillatory ventilation on vagal and phrenic nerve activities

This study was undertaken to define the mechanism for the respiratory inhibition observed during high-frequency oscillatory ventilation (HFOV). The effects of HFOV on the activities of single units in the vagus (Vna) and phrenic nerves (Pna) were examined in pentobarbital-anesthetized dogs. The animals were either ventilated by intermittent positive-pressure ventilation (IPPV) with and without positive end-expiratory pressure (PEEP), or by HFOV at a frequency of 25 Hz and pump displacement volume of 3 ml/kg. In 13 vagal units the Vna was much higher during HFOV than during IPPV or airway occlusion at a matched airway pressure. Ten units in the phrenic nerves were examined, and Pna (expressed as bursts/min) was attenuated by HFOV in all of them. In four of them, the effect of cooling the vagi to 8-10 degrees C on Pna was examined, and it was found that HFOV failed to alter the Pna. We conclude that 1) HFOV stimulates the pulmonary vagal afferent fibers continuously and to a degree greater than that due to static lung inflation and increased airway pressure and 2) the increased vagal activity during HFOV probably causes phrenic nerve activity inhibition.     

Elevation of superior vena caval pressure increases extravascular lung water after endotoxemia

In many sheep Escherichia coli endotoxin results in pulmonary hypertension, increased microvascular permeability, pulmonary edema, and increased central venous pressure. Since lung lymph drains into the systemic veins, increases in venous pressure may impair lymph flow sufficiently to enhance the accumulation of extravascular fluid. We tested the hypothesis that, following endotoxin, elevating the venous pressure would increase extravascular fluid. Thirteen sheep were chronically instrumented with catheters to monitor left atrial pressure (LAP), pulmonary arterial pressure (PAP), and superior vena caval pressure (SVCP) as well as balloons to elevate LAP and SVCP. These sheep received 4 micrograms/kg endotoxin, and following the pulmonary hypertensive spike the left atrial balloon was inflated so that (PAP + LAP)/2 = colloid osmotic pressure. It was necessary to control PAP + LAP in this way to minimize the sheep-to-sheep differences in the pulmonary hypertension. We elevated the SVCP to 10 or 17 mmHg or allowed it to stay low (3.2 mmHg). After a 3-h period, we killed the sheep and removed the right lungs for determination of the extravascular fluid-to-blood-free dry weight ratio (EVF). Sheep with SVCP elevated to 10 or 17 mmHg had significant increases in EVF (5.2 +/- 0.1 and 5.6 +/- 1.2) compared with the sheep in which we did not elevate SVCP (EVF = 4.5 +/- 0.4). These results indicate that sustained elevation in central venous pressure in patients contributes to the amount of pulmonary edema associated with endotoxemia.