Lung lymph flow during volume infusions

We investigated the effect of intravenous isotonic crystalloid solution infusion on lung lymph flow. Tracheobronchial lung lymph vessels were cannulated in 13 anesthetized dogs. The lymph flow rate was measured 1) with the lymph flowing against atmospheric pressure (QL), and 2) with the pressure at the outflow end of the lymph cannula equal to systemic venous pressure (QLV). QL and QLV were measured alternately in each lymph vessel. In one group of nine dogs, the base-line QL and QLV were 18 +/- 9 and 13 +/- 6 (SD) microliter/min, respectively (P less than 0.05). QL increased by 4.8 +/- 1.4-fold, and QLV increased by 3.5 +/- 2.1-fold during a 4-h infusion of 25 ml X kg-1 X h-1 of Ringer solution. QLV was significantly less than QL at all times. The increases in lymph flow were caused primarily by a reduction in the effective resistance of the lymph vessels with little rise in the pressure driving lymph from the lungs. Because QLV flowed against systemic venous pressure, the increase in QLV was blunted by a 3.1 +/- 2.3 cmH2O rise in venous pressure during the infusions. In the remaining four dogs, we infused Ringer solution rapidly in order to raise venous pressure to greater than 15 cmH2O. This caused QL to increase by 25 +/- 7-fold; however, QLV decreased to zero. We conclude that elevations in venous pressure which occur during volume infusions oppose lung lymph flow and lead to accumulation of excess fluid in the lungs.     

Effect of outflow pressure on lung lymph flow in unanesthetized sheep

Studies in anesthetized animals have shown that the flow rate from lung lymphatics (QL) depends on the pressure at the outflow end of the vessels (Po). We tested this in unanesthetized sheep prepared with chronic lung lymph cannula. We measured QL with the lymph cannula held at various heights above the olecranon and calculated Po as the height + QL X cannula resistance. QL decreased with increases in Po (delta QL/delta Po = -8.2 +/- 6.4 microliter X min-1 X cmH2O-1, mean +/- SD). We increased QL by raising left atrial pressure or infusing Ringer solution or Escherichia coli endotoxin and found that QL was even more sensitive to Po (delta QL/delta Po = -32 +/- 22). Cannula resistance caused a 9-70% reduction in QL. Changes in QL caused by increasing Po were not associated with changes in lymph protein concentration for up to 330 min. This indicates that increases in Po shunt lymph away from cannulated vessels but do not substantially effect microvascular filtration rate. The shunted lymph may flow into other vessels or collect in the lung. We conclude that QL does not accurately represent microvascular filtration rate because it depends on the cannula resistance and position at which the investigator chooses to place the cannula.     

Lung expansion and the perialveolar interstitial pressure gradient

We have determined the combined effects of lung expansion and increased extravascular lung water (EVLW) on the perialveolar interstitial pressure gradient. In the isolated perfused lobe of dog lung, we measured interstitial pressures by micropuncture at alveolar junctions (Pjct) and in adventitia of 30- to 50-microns microvessels (Padv) with stopped blood flow at vascular pressure of 3-5 cmH2O. We induced edema by raising vascular pressures. In nonedematous lobes (n = 6, EVLW = 3.1 +/- 0.3 g/g dry wt) at alveolar pressure of 7 cmH2O, Pjct averaged 0.5 +/- 0.8 (SD) cmH2O and the Pjct-Padv gradient averaged 0.9 +/- 0.5 cmH2O. After increase of alveolar pressure to 23 cmH2O the gradient was abolished in nonedematous lobes, did not change in moderately edematous lobes (n = 9, EVLW = 4.9 +/- 0.6 g/g dry wt), and increased in severely edematous lobes (n = 6, EVLW = 7.6 +/- 1.4 g/g dry wt). Perialveolar interstitial compliance decreased with increase of alveolar pressure. We conclude that increase of lung volume may reduce perialveolar interstitial liquid clearance by abolishing the Pjct-Padv gradient in nonedematous lungs and by compressing interstitial liquid channels in edematous lungs.     

Effect of interstitial edema on lung lymph flow in goats in the absence of filtration.

We tested the effect of interstitial edema on lung lymph flow when no filtration occurred. In 16 anesthetized open-thorax ventilated supine goats, we set pulmonary arterial and left atrial pressures to nearly zero and measured lymph flow for 3 h from six lungs without edema and ten with edema. Lymph flow decreased exponentially in all experiments as soon as filtration ceased. In the normal lungs the mean half time of the lymph flow decrease was 12.7 +/- 4.8 (SD) min, which was significantly shorter (P less than 0.05) than the 29.1 +/- 14.8 min half time in the edematous lungs. When ventilation was stopped, lymph flow in the edematous lungs decreased as rapidly as in the normal lungs. The total quantity of lymph after filtration ceased was 2.7 +/- 0.8 ml in normal lungs and 9.5 +/- 6.3 ml in edematous lungs, even though extravascular lung water was doubled in the latter (8.4 +/- 2.4 vs. 3.3 +/- 0.4 g/g dry lung, P less than 0.01). Thus the maximum possible clearance of the interstitial edema liquid by the lymphatics was 6.3 +/- 4.8%. When we restarted pulmonary blood flow after 1-2 h in four additional goats, lymph flow recovered within 30 min to the baseline level. These findings support the hypothesis that lung lymph flow originates mainly from alveolar wall perimicrovascular interstitial liquid and that the contribution of the lung lymphatic system to the clearance of interstitial edema (bronchovascular cuffs, interlobular septa) is small.     

Changes of deep cervical lymph flow following the infusion of isotonic, hypotonic, and hypertonic NaCl in rabbit.

Isotonic, hypotonic, or hypertonic saline was infused in anesthetized rabbits in order to test the effects of osmolality in cerebral vessels on lymph flow. The jugular lymph trunk was cannulated by PE tubing in a headward direction. Either a hypo-(100 mosmol), iso-(310 mosmol), or hypertonic (605 mosmol) NaCl solution was infused into the internal carotid artery (ICA) or the right lateral ventricle (RIV). Lymph was continuously collected at slight negative pressure, and measured over a 90 min preinfusion period, as well as during saline infusion and intermittent recovery periods. Mean peak flow rates for the first 30 min infusion of hypertonic saline via ICA and RLV were 5.1 +/- 1.2 and 6.7 +/- 1.6 microliters/min, respectively, or a significant increase of 38% and 40% over those of isotonic saline (3.7 +/- 0.9 microliters/min via ICA; 4.8 +/- 1.0 microliters/min via RLV). Conversely, for hypotonic saline, lymph flow rates were significantly reduced by 19% (2.9 +/- 0.6 microliters/min) and 23% (3.7 +/- 0.7 microliters/min) for the first 30 min infusion via ICA and RLV, respectively. Increases in arterial and intracranial pressures, as well as an enhancement of respiratory movements following hypertonic saline infusion, augmented lymph formation. The results suggest that the observed changes in jugular lymph flow following saline infusion can be correlated to the resulting increase in intracranial pressure and respiratory movements, and changes in the osmolality and blood pressure of cerebral vessels.     

Perialveolar interstitial resistance and compliance in isolated rat lung

We have developed a method to characterize fluid transport through the perialveolar interstitium using micropuncture techniques. In 10 experiments we established isolated perfused rat lung preparations. The lungs were initially isogravimetric at 10 cmH2O arterial pressure, 2 cmH2O venous pressure, and 5 cmH2O alveolar pressure. Perialveolar interstitial pressure was determined by micropuncture at alveolar junctions by use of the servo-null technique. Simultaneously a second micropipette was placed in an alveolar junction 20-40 microns away, and a bolus of albumin solution (3.5 g/100 ml) was injected. The resulting pressure transient was recorded for injection durations of 1 and 4 s in nonedematous lungs. The measurements were repeated after gross edema formation induced by elevated perfusion pressure. We model the interstitium as a homogeneous linearly poroelastic material and assume the initial pressure distribution due to the injection to be Gaussian. The pressure decay is inversely proportional to time, with time constant T, where T is a measure of the ratio of interstitial tissue stiffness to interstitial resistance to fluid flow. A linear regression was performed on the reciprocal of the pressure for the decaying portion of the transients to determine T. Comparing pressure transients in nonedematous and edematous lungs, we found that T was 4.0 +/- 1.4 and 1.4 +/- 0.6 s, respectively. We have shown that fluid transport through the pulmonary interstitium on a local level is sensitive to changes in interstitial stiffness and resistance. These results are consistent with the decreased stiffness and resistance in the perialveolar interstitium that accompany increased hydration.     

Lung fluid balance during acute renal failure in sheep

To determine whether uremia changes lung vascular permeability, we measured the flow of lymph and proteins from the lungs of acutely uremic sheep. Acute renal failure was induced by either bilateral nephrectomy or by reinfusing urine. Both models of renal failure increased the plasma creatinine from 0.8 +/- 0.3 to 11 +/- 1 mg/dl in 3 days but caused no significant change in the flow of lymph from the lungs. To determine whether uremia increased the protein clearance response to elevated pulmonary microvascular pressures, we inflated a balloon in the left atrium for 2 h before and 3 days after inducing acute renal failure. In seven sheep, before removing the kidneys, the 20 cmH2O elevation of left atrial pressure increased the protein clearance 3.9 +/- 3.0 ml/h (from 9.5 +/- 4.9 to 13.4 +/- 5.4 ml/h). Three days after the bilateral nephrectomy the same increase in left atrial pressure increased the protein clearance 6.4 +/- 3.6 ml/h (from 6.1 +/- 2.1 to 12.5 +/- 5.2 ml/h), which was a significantly larger increase than that measured before the nephrectomy (P less than 0.05). Sham nephrectomy in seven sheep caused the protein clearance response to the elevated left atrial pressure to fall from 4.7 +/- 1.9 ml/h before the sham nephrectomy to 2.6 +/- 1.4 ml/h 3 days later (P less than 0.05). Uremia due to reinfusion of urine in five sheep did not affect the protein clearance response to elevations in left atrial pressure. Neither model of acute uremia increased the postmortem extravascular lung water volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of airway and left atrial pressures on microcirculation of newborn lungs

To determine the effect of lung inflation and left atrial pressure on the hydrostatic pressure gradient for fluid flux across 20- to 60-microns-diam venules, we isolated and perfused the lungs from newborn rabbits, 7-14 days old. We used the micropuncture technique to measure venular pressures in some lungs and perivenular interstitial pressures in other lungs. For all lungs, we first measured venular or interstitial pressures at a constant airway pressure of 5 or 15 cmH2O with left atrial pressure greater than airway pressure (zone 3). For most lungs, we continued to measure venular or interstitial pressures as we lowered left atrial pressure below airway pressure (zone 2). Next, we inflated some lungs to whichever airway pressure had not been previously used, either 5 or 15 cmH2O, and repeated venular or interstitial pressures under one or both zonal conditions. We found that at constant blood flow a reduction of left atrial pressure below airway pressure always resulted in a reduction in venular pressure at both 5 and 15 cmH2O airway pressures. This suggests that the site of flow limitation in zone 2 was located upstream of venules. When left atrial pressure was constant relative to airway pressure, the transvascular gradient (venular-interstitial pressures) was greater at 15 cmH2O airway pressure than at 5 cmH2O airway pressure. These findings suggest that in newborn lungs edema formation would increase at high airway pressures only if left atrial pressure is elevated above airway pressure to maintain zone 3 conditions.     

Measurement of bronchial arterial blood flow and bronchovascular resistance in sheep

We studied the bronchial arterial blood flow (Qbr) and bronchial vascular resistance (BVR) in sheep prepared with carotid-bronchial artery shunt. Nine adult sheep were anesthetized, and through a left thoracotomy a heparinized Teflon-tipped Silastic catheter was introduced into the bronchial artery. The other end of the catheter was brought out through the chest wall and through a neck incision was introduced into the carotid artery. A reservoir filled with warm heparinized blood was connected to this shunt. The height of blood column in the reservoir was kept constant at 150 cm by adding more blood. Qbr was measured, after interrupting the carotid-bronchial artery flow, by the changes in the reservoir volume. The bronchial arterial back pressure (Pbr) was measured through the shunt when both carotid-bronchial artery and reservoir Qbr had been temporarily interrupted. The mean Qbr was 34.1 +/- 2.9 (SE) ml/min, Pbr = 17.5 +/- 3.3 cmH2O, BVR = 3.9 +/- 0.5 cmH2O X ml-1 X min, mean pulmonary arterial pressure = 21.5 +/- 3.6 cmH2O, and pulmonary capillary wedge pressure (Ppcw) = 14.3 +/- 3.7 cmH2O. We further studied the effect of increased left atrial pressure on these parameters by inflating a balloon in the left atrium. The left atrial balloon inflation increased Ppcw to 25.3 +/- 3.1 cmH2O, Qbr decreased to 21.8 +/- 2.4 ml/min (P less than 0.05), and BVR increased to 5.5 +/- 1.0 cmH2O.ml-1.min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Microvascular pressures measured by micropipettes in isolated edematous rabbit lungs

To study the mechanical effects of lung edema on the pulmonary circulation, we determined the longitudinal distribution of vascular resistance in the arteries, veins, and microvessels, and the distribution of blood flow in isolated blood-perfused rabbit lungs with varying degrees of edema. Active vasomotor changes were eliminated by adding papaverine to the perfusate. In three groups of lungs with either minimal [group I, mean wet-to-dry weight ratio (W/D) = 5.3 +/- 0.6 (SD), n = 7], moderate (group II, W/D = 8.5 +/- 1.2, n = 10), or severe (group III, W/D = 9.9 +/- 1.6, n = 5) edema, we measured by direct micropuncture the pressure in subpleural arterioles and venules (20-60 micron diam) and in the interstitium surrounding these vessels. We also measured pulmonary arterial and left atrial pressures and lung blood flow, and in four additional experiments we used radio-labeled microspheres to determine the distribution of blood flow during mild and severe pulmonary edema. In lungs with little or no edema (group I) we found that 33% of total vascular pressure drop was in arteries, 60% was in microvessels, and 7% was in veins. Moderate edema (group II) had no effect on total vascular resistance or on the vascular pressure profile, but severe edema (group III) did increase vascular resistance without changing the longitudinal distribution of vascular resistance in the subpleural microcirculation. Perivascular interstitial pressure relative to pleural pressure increased from 1 cmH2O in group I to 2 in group II to 4 in group III lungs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human recombinant tumor necrosis factor alpha infusion mimics endotoxemia in awake sheep

The macrophage-derived cytokine tumor necrosis factor alpha (TNF alpha) has been proposed as the major mediator of endotoxin-induced injury. To examine whether a single infusion of human recombinant TNF alpha (rTNF alpha) reproduces the pulmonary effects of endotoxemia, we infused rTNF alpha (0.01 mg/kg) over 30 min into six chronically instrumented awake sheep and assessed the ensuing changes in hemodynamics, lung lymph flow and protein concentration, and number of peripheral blood and lung lymph leukocytes. In addition, levels of thromboxane B2, 6-ketoprostaglandin F1 alpha, prostaglandin E2, and leukotriene B4 were measured in lung lymph. Pulmonary arterial pressure (Ppa) peaked within 15 min of the start of rTNF alpha infusion [base-line Ppa = 22.0 +/- 1.5 (SE) cmH2O; after 15 min of rTNF alpha infusion, Ppa = 54.2 +/- 5.4] and then fell toward base line. The pulmonary hypertension was accompanied by hypoxemia and peripheral blood and lung lymph leukopenia, both of which persisted throughout the 4 h of study. These changes were followed by an increase in protein-rich lung lymph flow (base-line lymph protein clearance = 1.8 +/- 0.4 cmH2O; 3 h after rTNF alpha infusion, clearance = 5.6 +/- 1.2), consistent with an increase in pulmonary microvascular permeability. Cardiac output and left atrial pressure did not change significantly throughout the experiment. Light-microscopic examination of lung tissue at autopsy revealed congestion, neutrophil sequestration, and patchy interstitial edema. We conclude that rTNF alpha induces a response in awake sheep remarkable similar to that of endotoxemia. Because endotoxin is a known stimulant of TNF alpha production, TNF alpha may mediate endotoxin-induced lung injury.     

Pulmonary lymphatic clearance of 99mTc-DTPA from air spaces during lung inflation and lung injury

A total of 22 sheep with lymphatic cannulas were used to determine if 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) clears directly from the air spaces of the lungs into the lymph vessels. Each sheep was anesthetized and ventilated with an aerosol of the DTPA for 2-5 min, and the DTPA activities in the lymph and plasma were measured every 15 min for 2 h. After the first 45 min, the average ratio of the DTPA in the lymph to that in the plasma (L/P) was 1.03 +/- 0.06 (SD) in the six control experiments and 1.11 +/- 0.05 in the six experiments in which the lungs were inflated with a positive end-expired pressure of 10 cmH2O throughout the study. Direct movement of the DTPA from the air spaces into the lymph was not necessary to account for the DTPA clearance in these experiments because the L/P ratio was not significantly different from 1.0. Eight additional sheep received intravenous infusions of air at 0.2 ml.kg-1.min-1 for 2 h to induce lung injury before depositing the DTPA. In these sheep L/P was 1.53 +/- 0.28, which was significantly higher than the value measured in the control group (P less than 0.01). We considered the possibility that the increased L/P ratio in these sheep could be due to alterations in the distribution of the blood flow to the tissue, but the L/P ratio in four sheep whose distribution of blood flow was altered by inflation of a balloon in the right pulmonary artery was 1.05 +/- 0.10, the same as the control value.(ABSTRACT TRUNCATED AT 250 WORDS)     

Longitudinal distribution of pulmonary vascular pressures as a function of postnatal age in rabbits.

The major purpose of this study was to determine whether the longitudinal distribution of pulmonary vascular pressures changes with postnatal age in rabbits. Using the direct micropuncture technique, we measured pressures in 20- to 80-microns-diam arterioles and venules in isolated lungs of rabbits of different postnatal ages. To determine the contribution of vasomotor tone, we added the vasodilator papaverine to the perfusate of some lungs of each age group. We compared vascular pressures measured at blood flow rates chosen to approximate in vivo cardiac outputs. In untreated lungs, the resistance across 20- to 80-microns-diam microvessels decreased from 12- to 72-h-old (0.022 +/- 0.009 cmH2O.min.kg.ml-1) to 5- to 15-day-old rabbits (0.008 +/- 0.007 cmH2O.min.kg.ml-1) and remained at this lower level in adults (0.013 +/- 0.008 cmH2O.min.kg.ml-1). In contrast, in papaverine-treated lungs, the resistance across 20- to 80-microns-diam microvessels did not change between 12- to 72-h-old (0.007 +/- 0.005 cmH2O.min.kg.ml-1) and 5- to 15-day-old rabbits (0.005 +/- 0.002 cmH2O.min.kg.ml-1) but increased between 5- to 15-day-old and adult rabbits (0.014 +/- 0.007 cmH2O.min.kg.ml-1). Thus vasomotor tone contributed to the postnatal change in the distribution of vascular pressures across lungs of rabbits.     

Effect of progressive exercise on lung fluid balance in sheep

The purpose of this study is to determine the roles of cardiac output and microvascular pressure on changes in lung fluid balance during exercise in awake sheep. We studied seven sheep during progressive treadmill exercise to exhaustion (10% grade), six sheep during prolonged constant-rate exercise for 45-60 min, and five sheep during hypoxia (fraction of inspired O2 = 0.12) and hypoxic exercise. We made continuous measurements of pulmonary arterial, left atrial, and systemic arterial pressures, lung lymph flow, and cardiac output. Exercise more than doubled cardiac output and increased pulmonary arterial pressures from 19.2 +/- 1 to 34.8 +/- 3.5 (SE) cmH2O. Lung lymph flow increased rapidly fivefold during progressive exercise and returned immediately to base-line levels when exercise was stopped. Lymph-to-plasma protein concentration ratios decreased slightly but steadily. Lymph flows correlated closely with changes in cardiac output and with calculated microvascular pressures. The drop in lymph-to-plasma protein ratio during exercise suggests that microvascular pressure rises during exercise, perhaps due to increased pulmonary venous pressure. Lymph flow and protein content were unaffected by hypoxia, and hypoxia did not alter the lymph changes seen during normoxic exercise. Lung lymph flow did not immediately return to base line after prolonged exercise, suggesting hydration of the lung interstitium.     

Effect of lung inflation on fluid flux in zone 1 lungs

Because of conflicting data in the literature, we studied the effect of positive-pressure inflation on transvascular fluid filtration in zone 1 lungs. Lungs from New Zealand White rabbits (n = 10) were excised, perfused with saline and autologous whole blood (1:1), ventilated, and continuously weighed. Pulmonary arterial and venous pressures (Pvas) were referenced to the most dependent part of the lung. A change in vascular volume (delta Vvas) and a fluid filtration rate (FFR) were calculated from the change in lung weight that occurred from 0 to 30 s and from 3 to 5 and 5 to 10 min, respectively, after changing alveolar pressure (PA). FFR's and delta Vvas's were measured with Pvas equal to 2 or 10 cmH2O and PA changing from 15 to 30 cmH2O when the lungs were normal and after they were made edematous. When Pvas = 2 cmH2O, increasing PA increased the Vvas and the FFR in both normal and edematous lungs. However, when Pvas = 10 cmH2O, increasing PA only slightly changed the Vvas and reduced the FFR in the normal lungs, and decreased Vvas and markedly decreased the FFR in the presence of edema. Inflating zone 1 lungs by positive pressure has an effect on transvascular fluid flux that depends on the Pvas. The results suggest that the sites of leakage in zone 1 also vary depending on Pvas and PA.     

Properties of steady maximal expiratory flow within excised canine central airways

Using our transistor model of the lung during forced expiration (J. Appl. Physiol. 62: 2013-2025, 1987), we recently predicted that 1) axially arranged choke points can exist simultaneously during forced expiration with sufficient effort, and 2) overall maximal expiratory flow may be relatively insensitive to nonuniform airways obstruction because of flow interdependence between parallel upstream branches. We tested these hypotheses in excised central airways obtained from five canine lungs. Steady expiratory flow was induced by supplying constant upstream pressure (Pupstream = 0-16 cmH2O) to the bronchi of both lungs while lowering pressure at the tracheal airway opening (16 to -140 cmH2O). Intra-airway pressure profiles obtained during steady maximal expiratory flow disclosed a single choke point in the midtrachea when Pupstream was high (2-16 cmH2O). However, when Pupstream was low (0 cmH2O), two choke sites were evident: the tracheal site persisted, but another upstream choke point (main carina or both main bronchi) was added. Flow interdependence was studied by comparing maximal expiratory flow through each lung before and after introduction of a unilateral external resistance upstream of the bronchi of one lung. When this unilateral resistance was added, ipsilateral flow always fell, but changes in flow through the contralateral lung depended on the site of the most upstream choke. When a single choke existed in the trachea, addition of the external resistance increased contralateral flow by 38 +/- 28% (SD, P less than 0.003). In contrast, when the most upstream choke existed at the main carina or in the bronchi, addition of the external resistance had no effect on contralateral maximal expiratory flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Air interface and elastic recoil affect vascular resistance in three zones of rabbit lungs

We examined the effect of the air interface on pulmonary vascular resistance (PVR) in zones 1, 2, and 3 by comparing pressure-flow data of air- and liquid-filled isolated rabbit lungs. Lungs were perfused with Tyrode's solution osmotically balanced with 1% albumin and 4% dextran and containing the vasodilator papaverine (0.05 mg/ml). Lung volume was varied by negative pleural pressure form 0 to -25 cmH2O. Pulmonary artery (Ppa) and venous (Ppv) pressures were fixed at various levels relative to the lung base. Alveolar pressure (PA) was always zero, and perfusate flow was measured continuously. In zone 1 Ppa was -2.5 cmH2O and Ppv was -15 cmH2O. In zone 2 Ppa was 10 cmH2O and Ppv was -5 cmH2O. In zone 3 Ppa was 15 cmH2O and Ppv was 8 cmH2O. We found that in zone 1 the interface was essential for perfusion, but in zones 2 and 3 it had much lesser effects. In general, PVR depended almost uniquely (i.e., with small hysteresis) on transpulmonary pressure, whereas a large hysteresis existed between PVR and lung volume. PVR was high in collapsed and especially in atelectatic lungs, fell sharply with moderate inflation, and within the ranges of vascular pressure studied did not rise again toward total lung capacity. These results suggest that in zone 1 the interface maintains the patency of some alveolar vessels, probably in corners. The majority of alveolar septal vessels appears to be exposed directly to PA in zones 2 and 3, because at equal transpulmonary pressure the PVR is similar in the presence or absence of an interface.     

Oxygen-induced lung microvascular injury in neutropenic rabbits and lambs

We did two studies to see if severe neutropenia might reduce the severity or delay development of O2-induced lung microvascular injury. First, we treated 11 rabbits with nitrogen mustard until their circulating neurophil count decreased to less than 50/microliters of blood, after which the rabbits breathed pure O2 until death; nine other rabbits received no nitrogen mustard and had normal numbers of circulating neutrophils during O2 breathing. All rabbits died of respiratory failure with pulmonary edema, and although chemotherapy decreased the number of neutrophils in the lungs by greater than 90%, it did not influence survival time or extravascular lung water content. To see if severe neutropenia might slow the development of O2-induced lung microvascular injury, we assessed the effects of sustained hyperoxia on lung fluid balance in unanesthetized lambs treated with hydroxyurea, so that their absolute neutrophil count was less than 50/microliters of blood. We measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma during a 2- to 4-h control period and then daily for 2 to 4 h as the lambs continuously breathed pure O2. After 3 days of hyperoxia, lymph flow doubled and the concentration of protein in lymph increased from 3.3 +/- 0.5 to 4.2 +/- 0.3 g/dl. Tracer studies with 125I-albumin before and 3 days after the start of O2 breathing confirmed the development of increased lung vascular permeability to protein. All lambs died of respiratory failure with pulmonary edema after 3-5 days in O2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of increased surface tension and assisted ventilation on 99mTc-DTPA clearance

Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of 99mTc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreased arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. 99mTc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP [k = 7.57 +/- 0.71%/min (SE)] and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearance curves were biexponential in the former two groups. We conclude that pulmonary clearance of 99mTc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure.     

Inspiratory muscles during exercise: a problem of supply and demand

The capacity of inspiratory muscles to generate esophageal pressure at several lung volumes from functional residual capacity (FRC) to total lung capacity (TLC) and several flow rates from zero to maximal flow was measured in five normal subjects. Static capacity was 126 +/- 14.6 cmH2O at FRC, remained unchanged between 30 and 55% TLC, and decreased to 40 +/- 6.8 cmH2O at TLC. Dynamic capacity declined by a further 5.0 +/- 0.35% from the static pressure at any given lung volume for every liter per second increase in inspiratory flow. The subjects underwent progressive incremental exercise to maximum power and achieved 1,800 +/- 45 kpm/min and maximum O2 uptake of 3,518 +/- 222 ml/min. During exercise peak esophageal pressure increased from 9.4 +/- 1.81 to 38.2 +/- 5.70 cmH2O and end-inspiratory esophageal pressure increased from 7.8 +/- 0.52 to 22.5 +/- 2.03 cmH2O from rest to maximum exercise. Because the estimated capacity available to meet these demands is critically dependent on end-inspiratory lung volume, the changes in lung volume during exercise were measured in three of the subjects using He dilution. End-expiratory volume was 52.3 +/- 2.42% TLC at rest and 38.5 +/- 0.79% TLC at maximum exercise.(ABSTRACT TRUNCATED AT 250 WORDS)