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)     

Nature of pulmonary hypertension in canine oleic acid pulmonary edema

It has recently been suggested that pulmonary hypertension secondary to oleic acid lung injury mainly results from an increase in the critical closing pressure of the pulmonary vessels [Boiteau et al., Am. J. Physiol. 251 (Heart Circ. Physiol. 20): H1163-H1170, 1986]. To further test this hypothesis, we studied 1) the pulmonary arterial pressure- (Ppa) flow (Q) relationship with left atrial pressure (Pla) kept constant (n = 7) and 2) the Ppa-Pla relationship with Q kept constant (n = 9) in intact anesthetized and ventilated dogs before and after lung injury induced by oleic acid (0.09 ml/kg iv). Q was manipulated by use of a femoral arteriovenous bypass and a balloon catheter inserted in the inferior vena cava. Pla was manipulated with a balloon catheter placed by thoracotomy in the left atrium. Ppa-Q plots were rectilinear before as well as after oleic acid. Before oleic acid, the extrapolated pressure intercept of the Ppa-Q plots approximated Pla. Oleic acid administration resulted in a parallel shift of the Ppa-Q plots to higher pressure; i.e., the pressure intercept increased, whereas the slope was not modified. Increasing Pla at constant Q before oleic acid led to a proportional augmentation of Ppa. After oleic acid, however, changes in Pla over the same range affected Ppa only at the highest levels of Pla. These results suggest that oleic acid lung injury increases the critical closing pressure that exceeds Pla, becomes the effective outflow pressure of the pulmonary circulation, and is responsible for the pulmonary hypertension.     

Effects of embolus size on hemodynamics and gas exchange in canine embolic pulmonary hypertension

We examined the effects of different-sized glass-bead embolization on pulmonary hemodynamics and gas exchange in 12 intact anesthetized dogs. Pulmonary hemodynamics were evaluated by multipoint pulmonary arterial pressure (Ppa)/cardiac output (Q) plots before and 60 min after sufficient amounts of 100-microns (n = 6 dogs) or 1,000-microns (n = 6 dogs) glass beads to triple baseline Ppa were given and again 20 min after 5 mg/kg hydralazine in all the animals. Gas exchange was assessed using the multiple inert gas elimination technique in each of these experimental conditions. Embolization increased both the extrapolated pressure intercepts (by 6 mmHg) and the slopes (by 5 mmHg.l-1.min.m2) of the linear Ppa/Q plots, together with an 80% angiographic pulmonary vascular obstruction. These changes were not significantly different in the two subgroups of dogs. However, arterial PO2 was most decreased after the 100-microns beads, and arterial PCO2 was most increased after the 1,000-microns beads. Both bead sizes deteriorated the distribution of ventilation (VA)/perfusion (Q) ratios, with development of lung units with higher as well as with lower than normal VA/Q. Only 100-microns beads generated a shunt. Only 1,000-microns beads generated a high VA/Q mode and increased inert gas dead space. Hydralazine increased the shunt and decreased the slope of the Ppa/Q plots after 100-microns beads and had no effect after 1,000-microns beads. We conclude that in embolic pulmonary hypertension, Ppa/Q characteristics are unaffected by embolus size up to 1,000 microns.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Effects of increased pulmonary vascular tone on gas exchange in canine oleic acid pulmonary edema

Pulmonary gas exchange was investigated before and after an increase in pulmonary vascular tone induced by administration of acetylsalicylic acid (ASA), indomethacin, or almitrine in 32 pentobarbital-anesthetized and ventilated (fraction of inspired O2 0.4) dogs with oleic acid lung injury. Pulmonary vascular tone was evaluated by five-point pulmonary arterial pressure (PAP)/cardiac index (Q) plots and intrapulmonary shunt was measured using a SF6 infusion. PAP/Q plots were rectilinear in all experimental conditions. In control dogs (n = 8), oleic acid (0.09 ml/kg iv) increased PAP over the range of Q studied (1-5 l.min-1.m-2). At the same Q, arterial PO2 fell from 186 +/- 11 to 65 +/- 8 (SE) Torr and intrapulmonary shunt rose from 5 +/- 1 to 50 +/- 6% 90 min after oleic acid injection. These changes remained stable during the generation of two consecutive PAP/Q plots. ASA (1 g iv, n = 8), indomethacin (2 mg/kg iv, n = 8), and almitrine (8 micrograms.kg-1.min-1 iv, n = 8) produced a further increase in PAP at each level of Q. ASA and indomethacin, respectively, increased arterial PO2 from 61 +/- 4 to 70 +/- 3 Torr (P less than 0.05) and from 70 +/- 6 to 86 +/- 6 Torr (P less than 0.05) and decreased intrapulmonary shunt from 61 +/- 5 to 44 +/- 4% (P less than 0.05) and from 44 +/- 5 to 29 +/- 4% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

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 continuous positive-pressure ventilation in experimental pulmonary edema.

We compared the effects of continuous positive-pressure ventilation (CPPV), using 10 cmH2O positive end-expiratory pressure (PEEP), with intermittent positive-pressure ventilation (IPPV), on pulmonary extravascular water volume (PEWV) and lung function in dogs with pulmonary edema caused by elevated left atrial pressure and decreased colloid osmotic pressure. The PEWV was measured by gravimetric and double-isotope indicator dilution methods. Animals with high (22-33 mmHg), moderately elevated (12-20 mmHg), and normal (3-11 mmHg) left atrial pressures (Pla) were studied. The PEWV by both methods was significantly increased in the high and moderate Pla groups, the former greater than the latter (P less than 0.05). There was no difference in the PEWV between animals receiving CPPV and those receiving IPPV in both the high and moderately elevated Pla groups. However, in animals with high Pla, the Pao2 was significantly better maintained and the inflation pressure required to deliver a tidal volume of 12 ml/kg was significantly less with the use of CPPV than with IPPV. We conclude that in pulmonary edema associated with high Pla, PEEP does not reduce PEWV but does improve pulmonary function.     

Response of pulmonary veins to increased intracranial pressure and pulmonary air embolization

Brain compression with subdural air causes pulmonary hypertension and noncardiogenic pulmonary edema (A. B. Malik, J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42: 335-343, 1977). To see whether air emboli to the lungs rather than brain compression caused these findings, anesthetized dogs received intravenous air infusions, subdural air infusions, or brain compression from balloons inflated in the subdural space. Subdural air and intravenous air resulted in similar vascular responses. Pulmonary artery pressure (Ppa) increased 160% (P less than 0.01) and pulmonary venous pressure transiently rose 13 +/- 5 Torr (P less than 0.05) without an increase in left atrial pressure or cardiac output (Q). The end-tidal PCO2 fell 55% (P less than 0.01) and the postmortem weight of the lungs increased 55% (P less than 0.05). Brain compression with a subdural balloon instead of air only caused a 20% rise in Ppa and Q without pulmonary edema. Thus, pulmonary air emboli rather than brain compression accounts for the edema and pulmonary hypertension caused by subdural air. Catheters in pulmonary veins and the left atrium showed that air emboli cause transient pulmonary venous hypertension as well as a reproducible form of noncardiogenic pulmonary endema.     

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

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

Increased pulmonary microvasuclar permeability induced by alpha-naphthylthiourea

The effects of alpha-naphthylthiourea (ANTU) on lung microvascular permeability to plasma proteins were studied in anesthetized open-chest dogs. Lymph flow (Jv) was recorded, and total protein in plasma and lymph was analyzed after cannulating a small prenodal lung lymphatic. The protocol involved four experimental periods. Period 1. During this base-line period the preparation stabilized and steady states were reached in Jv, lymph total protein, pulmonary arterial pressure (Ppa), and left atrial pressure (Pla). Period 2. Pla was increased to approximately 20 cmH2O and maintained at that level until Jv and protein measurements attained a new steady state. Period 3. After Pla was lowered to control levels, ANTU (5 mg/kg body wt) was infused intravenously and parameters were measured for 3 h. Period 4 Pla was again raised to the pre-ANTU levels of period 2 and maintained for an additional 2-3 h. The lymphatic total protein clearance increased 8.6-fold for an equivalent increase in pulmonary capillary pressure after ANTU. Vascular permeability was assessed by estimating the osmotic reflection coefficient (sigma d) for total protein at the pulmonary capillary membrane. Sigma d decreased from 0.65 to 0.40 following ANTU. From plasma protein fractions in four experiments, equivalent pore radii for the capillary membrane of 95 and 280 A were calculated after ANTU compared with 80 and 200 A for normal lung capillaries. In addition, extravascular lung water increased from 3.8 +/- 0.16 to 5.87 +/- 0.25 following ANTU and to 7.55 +/- 0.55 (g/g blood-free dry wt) when Pla was elevated with ANTU. The experimental design allowed quantitative assessment of the vascular permeability increase after ANTU by use of lymph protein fluxes that had minimal errors due to changes in surface area or lymph contamination from nonpulmonary structures.     

Compliance of the main pulmonary artery during the ventilatory cycle.

Transmural pulmonary arterial pressure (Ppa), diameter (D), and length (L) of a segment of the main pulmonary artery (MPA) were measured simultaneously in anesthetized open-chest dogs. The instantaneous volume was calculated from D and L. Pulmonary arterial elasticity for diameter (EpD) was calculated as the ratio of the amplitude of Ppa to D oscillation normalized by the mean D. Similar indexes were calculated for L (EpL) and V (Epv). Compliance per unit length was calculated from the dimensions and elasticity of the MPA. Under control conditions with 5 cmH2O positive end-expiratory pressure, EpD, EpL, and Epv at cardiac frequency were 175 +/- 27, 147 +/- 27, and 55 +/- 7 cmH2O, respectively. EpD increased with positive end-expiratory pressure, but EpL decreased and Epv was unaffected. EpD, EpL, Epv, and compliance per unit length were not significantly different between the start of inspiration and the start of expiration. In addition, there were no significant phase differences between the oscillations of Ppa and V at respiratory frequency. We conclude that the previously reported time variation of pulmonary arterial compliance during the ventilatory cycle is not due to time-varying properties of the MPA.     

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.     

Sinoaortic deafferentation reduces intrapulmonary shunt in dogs with oleic acid lung injury

Hypoxic stimulation of the peripheral chemoreceptors has been reported to inhibit hypoxic pulmonary vasoconstriction. To evaluate the pathophysiological importance of this observation, we investigated the effects of surgical peripheral chemoreceptor denervation on pulmonary vascular tone and gas exchange in 17 pentobarbital-anesthetized dogs with oleic acid pulmonary edema. Pulmonary arterial pressure-cardiac index (Ppa/Q) plots, blood gases, and intrapulmonary shunt measured by the SF6 method were obtained at base line, after peripheral chemodenervation (n = 9) or after sham operation (n = 8), and again after 0.09 ml.kg-1 intravenous oleic acid. Over the range of Q studied (2-5 l.min-1.m-2), Ppa/Q plots were best fitted as first-order polynomials in most dogs in all experimental conditions. Chemoreceptor denervation increased Ppa at the lowest Q, while sham operation did not affect the Ppa/Q plots. Oleic acid increased Ppa over the entire range of Q and increased intrapulmonary shunt. This latter was measured at identical Q during the construction of the Ppa/Q plots. Chemoreceptor-denervated dogs, compared with sham-operated dogs, had the same pulmonary hypertension but lower intrapulmonary shunt (36 +/- 4 vs. 48 +/- 5%, means +/- SE, P less than 0.04) and venous admixture (43 +/- 4 vs. 54 +/- 3%, P less than 0.02). We conclude that in intact dogs chemoreceptor denervation attenuates the rise in intrapulmonary shunt after oleic acid lung injury. Whether this improvement in gas exchange is related to an enhanced hypoxic pulmonary vasoconstriction is uncertain.     

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.     

Increased fragility of pulmonary capillaries in newborn rabbit

The pulmonary capillaries of neonatal lungs are potentially vulnerable to stress failure because of the complex changes in the pulmonary circulation that occur at birth. We perfusion fixed the lungs from nine anesthetized newborn rabbits at capillary transmural pressures (P(tm)) of 5 +/- 5, 10 +/- 5, and 15 +/- 5 cmH(2)O. Normal microscopic appearances were seen at P(tm) values of 5 +/- 5 and 10 +/- 5 cmH(2)O, but massive airway edema was observed in lungs perfused at a P(tm) of 15 +/- 5 cmH(2)O. Consistent with this, no disruptions of the alveolar epithelium were observed at P(tm) values of 5 +/- 5 cmH(2)O, but mean values of 0.11 and 1.22 breaks/mm epithelium were found at P(tm) of 10 +/- 5 and 15 +/- 5 cmH(2)O, respectively (P < 0.05 for 5 +/- 5 vs. 15 +/- 5 cmH(2)O). These pressures are in striking contrast to those in the adult rabbit in which, by a similar procedure, a P(tm) of 52.5 cmH(2)O, is required before stress failure is consistently seen. We conclude that stress failure of pulmonary capillaries in newborn rabbit lungs can occur at P(tm) values of less than one-third of those that are required in adult lungs.     

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.     

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.     

Neural antagonists modulate pulmonary vascular pressure-flow plots in conscious dogs

Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed in conscious dogs during normoxia by graded constriction of the thoracic inferior vena cava to reduce Q. P/Q plots were generated with the autonomic nervous system (ANS) intact and following total autonomic ganglionic block, cholinergic block, and sympathetic alpha- and beta-adrenergic block alone and in combination. With the ANS intact, the relationship between the pulmonary vascular pressure gradient [pulmonary arterial pressure (PAP)--pulmonary capillary wedge pressure (PCWP)] and Q was linear with an extrapolated pressure intercept of 0 mmHg. Total autonomic ganglionic block increased PAP-PCWP over the entire range of Q studied (60-140 ml . min-1 . kg-1). Cholinergic block resulted in a small increase in PAP-PCWP at a Q of 60 ml . min-1 . kg-1, a small decrease in PAP-PCWP at a Q of 140 ml . min-1 . kg-1, but no change in PAP-PCWP over the midrange of Q. Sympathetic beta-adrenergic block increased, and sympathetic alpha-adrenergic block decreased PAP-PCWP over the entire range of Q studied. Combined sympathetic alpha- and beta-adrenergic block also increased PAP-PCWP at each level of Q. Thus the ANS, either directly or via circulating catecholamines, exerts an active regulatory influence on the pulmonary vascular P/Q relationship of intact conscious dogs during normoxia over a wide range of Q. Activation of sympathetic beta-adrenergic receptors results in pulmonary vasodilatation, whereas, alpha-receptor activation results in vasoconstriction. Surprisingly, based on the effects of total autonomic ganglionic block and combined sympathetic alpha- and beta-adrenergic block, the net effect of the ANS on PAP-PCWP/Q during normoxia appears to be pulmonary vasodilatation.     

Effects of sildenafil on hypoxic pulmonary vascular function in dogs.

Sildenafil has been shown to be an effective treatment of pulmonary arterial hypertension and is believed to present with pulmonary selectivity. This study was designed to determine the site of action of sildenafil compared with inhaled nitric oxide (NO) and intravenous sodium nitroprusside (SNP), known as selective and nonselective pulmonary vasodilators, respectively. Inhaled NO (40 ppm), and maximum tolerated doses of intravenous SNP and sildenafil, (5 microg x kg(-1) x min(-1) and 0.1 mg x kg(-1) x h(-1)), respectively, were administered to eight dogs ventilated in hypoxia. Pulmonary vascular resistance (PVR) was evaluated by pulmonary arterial pressure (Ppa) minus left atrial pressure (Pla) vs. flow curves, and partitioned into arterial and venous segments by the occlusion method. Right ventricular hydraulic load was defined by pulmonary arterial characteristic impedance (Zc) and elastance (Ea) calculations. Right ventricular arterial coupling was estimated by the ratio of end-systolic elastance (Ees) to Ea. Decreasing the inspired oxygen fraction from 0.4 to 0.1 increased Ppa - Pla at a standardized flow of 3 l x min(-1) x m(-2) from 6 +/- 1 to 18 +/- 1 mmHg (mean +/- SE). Ppa - Pla was decreased to 9 +/- 1 by inhaled NO, 14 +/- 1 by SNP, and 14 +/- 1 mmHg by sildenafil. The partition of PVR, Zc, Ea, and Ees/Ea was not affected by the three interventions. Inhaled NO did not affect systemic arterial pressure, which was similarly decreased by sildenafil and SNP, from 115 +/- 4 to 101 +/- 4 and 98 +/- 5 mmHg, respectively. We conclude that inhaled NO inhibits hypoxic pulmonary vasoconstriction more effectively than sildenafil or SNP, and sildenafil shows no more selectivity for the pulmonary circulation than SNP.     

Effect of PEEP and type of injury on thermal-dye estimation of pulmonary edema

We investigated the effect of positive end-expiratory pressure (PEEP) on the extravascular thermal volume of the lung (ETV) determined by the thermal-dye technique in three canine models of pulmonary edema created by injection of alpha-naphthylthiourea (ANTU) or oleic acid (OA) into the pulmonary circulation or intrabronchial instillation of hydrochloric acid (HCl). ETV was determined before, during, and after ventilation with 14 cmH2O PEEP, and final ETV was compared with the extravascular lung mass (ELM) determined postmortem. Final ETV correctly estimated ELM in 12 animals with ANTU injury, ETV/ELM = 1.04 +/- 0.13, but underestimated after HCl injury (n = 5), ETV/ELM = 0.61 +/- 0.23, and OA injury (n = 6), ETV/ELM = 0.73 +/- 0.19. Whereas PEEP had no consistent effect on extravascular thermal volume in ANTU edema, there was a reversible increase in ETV during PEEP in animals with HCl or OA injury and underestimation of ELM. The increase in ETV during PEEP averaged 9.3 +/- 3.8 ml/kg (62 +/- 42%) over the mean of the pre- and post-PEEP values after HCl injury (P less than 0.01) and 6.7 +/- 4.4 ml/kg (47 +/- 35%) after OA injury (P less than 0.02). There was an inverse correlation between the change in ETV during PEEP and the ETV/ELM ratio for animals with HCl and OA injury (r = -0.94). We conclude that PEEP produces a reversible increase in ETV in some models of lung injury by allowing for distribution of thermal indicator through a larger fraction of the lung water and that this response may be useful to detect underestimation when gravimetric measurements are not available.