Lymph flow from edematous dog lungs

We measured the flow rate (QLV) from cannulated lung lymph vessels in anesthetized dogs. Low-resistance lymph cannulas were used and the vessels were cannulated at the lung hilus. When we increased left atrial pressure to 42.9 +/- 5.7 (SD) cmH2O (base line = 6.6 +/- 4.6 cmH2O), the lungs became edematous and QLV increased from a base line of 20.4 +/- 21.5 microliters/min to 388 +/- 185 microliters/min. QLV plateaued at the higher level. We also measured the relationship between lymph flow rate and the height of the outflow end of the lymph cannula. From this relationship, determined at the end of the period of elevated left atrial pressure, we calculated the effective resistance and pressure driving lymph from the lungs. We also cannulated lymph vessels in the downstream direction and estimated the effective resistance and pressure opposing flow into the part of the lymphatic system between the lung hilus and the veins (extrapulmonary lymph vessels). We found that the effective resistance of the extrapulmonary part of the lymph system (0.042 +/- 0.030 (SD) cmH2O X min X microliter-1) was large compared with the resistance of the lymph vessels from the lungs (0.026 +/- 0.027). These data indicate that the resistance of the extrapulmonary part of the lung lymph system limits the maximum flow of lymph from edematous 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 overexpansion increases pulmonary microvascular protein permeability in young lambs

To study the effects of inflation pressure and tidal volume (VT) on protein permeability in the neonatal pulmonary microcirculation, we measured lung vascular pressures, blood flow, lymph flow (QL), and concentrations of protein in lymph (L) and plasma (P) of 22 chronically catheterized lambs that received mechanical ventilation at various peak inflation pressures (PIP) and VT. Nine lambs were ventilated initially with a PIP of 19 +/- 1 cmH2O and a VT of 10 +/- 1 ml/kg for 2-4 h (base line), after which we overexpanded their lungs with a PIP of 58 +/- 3 cmH2O and a VT of 48 +/- 4 ml/kg for 4-8 h. QL increased from 2.1 +/- 0.4 to 13.9 +/- 5.0 ml/h. L/P did not change, but the ratio of albumin to globulin in lymph relative to the same ratio in plasma decreased, indicating altered protein sieving in the pulmonary microcirculation. Seven other lambs were mechanically ventilated for 2-4 h at a PIP of 34 +/- 1 cmH2O and a VT of 23 +/- 2 ml/kg (base line), after which their chest and abdomen were bound so that PIP increased to 54 +/- 1 cmH2O for 4-6 h without a change in VT. QL decreased on average from 2.8 +/- 0.6 to 1.9 +/- 0.3 ml/h (P = 0.08), and L/P was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fluid balance in sheep lungs before and after extracorporeal perfusion

Lung fluid balance was studied in sheep under the following conditions: 1) unanesthetized, standing in a metabolic cage; 2) anesthetized, in a supine position; 3) 1 h after extracorporeal perfusion; and 4) either 4-6 h after extracorporeal perfusion (i.e., control experiments) or 1.5 h after left atrial pressure was increased by 15 cmH2O. Lung lymph flow rate (QL), plasma and lymph concentrations for nine protein fractions, urea permeability-surface area product (PS), urea effective diffusivity (D1/2S), and extravascular lung water (VE) were measured under each condition. Bloodless wet and dry lung weights were measured at the end of each experiment. QL increased and lymph-to-plasma concentration ratio for total proteins (L/P) decreased after the sheep were anesthetized and placed in a supine position. This possibly resulted from an increase in microvascular pressure induced by anesthesia and/or reorientation of the lungs. PS, D1/2S, and VE decreased, indicating a decrease in perfused surface area associated with a decreased cardiac output or alteration in lung orientation. After 90 min of extracorporeal perfusion, no significant differences were found in QL, PS, and D1/2S compared with those measured during the anesthetized period. No changes in PS or D1/2S could be detected after an average of 4.2 h of extracorporeal perfusion. The average bloodless wet-to-dry lung weight ratio [(W-D)/D] was 3.77 +/- 0.12, well within the range for normal sheep lungs. An increase in venous pressure of 15 cmH2O produced a response similar to that observed in the unanesthetized sheep lung lymph preparation: QL increased, L/P decreased, PS and D1/2S did not increase, and VE and (W-D)/D increased slightly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Portal venous infusions of L-glutamine in anaesthetized dogs do not influence renal function.

It has been reported that the intraportal infusion of glutamine in Munich-Wistar rats will cause depression of renal perfusion and the urinary excretion of salt and water. We have attempted to reproduce these findings in anaesthetized dogs. L-Glutamine was infused at doses between 120 and 150 mumol/min into the portal vein and femoral vein of anaesthetized dogs. No effect was observed on portal venous pressure, blood pressure, or kidney function. Similar data were obtained with D-glutamine. Liver biopsy revealed no abnormalities. When 1.5-3 micrograms histamine (free base) was infused into the portal system, portal venous pressure rose from 15.2 +/- 0.33 to 24.8 +/- 0.40 cmH2O (p < 0.05) (1 cmH2O = 98.1 Pa). Glutamine infusions do not appear to initiate hepatorenal reflexes in dogs as they have been reported to do in rats.     

Effect of isoproterenol or exercise on pulmonary lymph flow and hemodynamics

Experiments were performed to determine whether different methods of increasing cardiac output would have similar effects on lung lymph flow, and to assess the contribution of the microvasculature (fluid-exchanging vessels) to the total calculated pulmonary vascular resistance. Yearling unanesthetized sheep with chronic vascular catheters and lung lymph fistulas underwent intravenous infusions of isoproterenol at 0.2 micrograms X kg-1. min-1 (n = 8) or were exercised on a treadmill (n = 16). Both isoproterenol and exercise increased cardiac output, lowered calculated total pulmonary and systemic vascular resistances, and had no effect on the calculated pulmonary microvascular pressure. Isoproterenol infusions did not affect lung lymph flow, whereas exercise increased lung lymph flow in proportion to the increase in cardiac output. We conclude that 1) the sheep has a different pulmonary hemodynamic response to exercise than dogs and man, 2) the microvasculature is recruited during exercise-induced but not isoproterenol-induced increases in cardiac output, and 3) the microvasculature represents only a small proportion of the total calculated pulmonary vascular resistance.     

Regional differences in interstitial fluid albumin concentration in edematous lamb lungs.

We have determined regional lung interstitial fluid albumin concentration in lambs with hydrostatic pulmonary edema and correlated it with lung lymph and plasma albumin concentrations. In anesthetized lambs, we raised left atrial pressure to 25-30 cmH2O by obstructing the aorta and volume overloading the lambs with infusions of Ringer lactate solution (group I, n = 10) or sheep's blood (group II, n = 9). We measured lung lymph flow and concentrations of total protein and albumin in plasma and lymph. With micropipettes we also collected interstitial fluid from interlobular septal pools and peribronchial, periarterial, and perivenous liquid cuffs near the hilum for measurement of albumin concentration by the gel immunoelectrophoresis method. In both groups, lung lymph flow increased with left atrial hypertension, and the ratio of lymph to plasma protein concentration fell. For group I, plasma and lymph albumin concentrations during the phase of hydrostatic edema were 1.97 +/- 0.49 and 1.15 +/- 0.36, respectively; for group II, they were 3.77 +/- 0.42 and 2.43 +/- 0.39 g/dl, respectively. Lung wet-to-dry weight ratio averaged 6.0 in both groups. Albumin concentration was always lower in interstitial fluid than in plasma. In both groups, albumin concentration was similar in periarterial and peribronchial fluid cuffs (group I 1.19 +/- 0.6 and 1.36 +/- 0.79 g/dl, respectively; group II 2.87 +/- 1.05 and 2.33 +/- 0.58 g/dl, respectively) but was always greater than that in perivenous and interlobular septal pools (group I 0.61 +/- 0.21 and 0.67 +/- 0.23 g/dl, respectively; group II 1.76 +/- 0.49 and 1.55 +/- 0.52 g/dl, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dextran sulfate inhibits PMN-dependent hydrostatic pulmonary edema induced by tumor necrosis factor.

We tested the hypothesis that neutrophil sequestration is required for the development of tumor necrosis factor- (TNF) induced neutrophil- (PMN) dependent pulmonary edema. TNF (3.2 X 10(5) U/kg ip) was injected into guinea pigs 18 h before lung isolation. After isolation, the lung was perfused with a phosphate-buffered Ringer solution. Dextran sulfate (mol wt 500,000) prevented the changes in pulmonary capillary pressure (Ppc; 8.5 +/- 0.8 vs. 12.8 +/- 0.8 cmH2O), lung weight gain (dW; +0.240 +/- 0.135 vs. +1.951 +/- 0.311 g), and pulmonary edema formation or wet-to-dry wt ratio [(W - D)/D; 6.6 +/- 0.2 vs. 8.3 +/- 0.5] at 60 min induced by PMN infusion into a TNF-pretreated lung. The unsulfated form of dextran had no protective effect [Ppc, dW, and (W - D)/D at 60 min: 11.9 +/- 0.9 cmH2O, +1.650 +/- 0.255 g, and 7.3 +/- 0.2, respectively], whereas the use of another anionic compound, heparin, inhibited the TNF + PMN response [Ppc, dW, and (W - D)/D at 60 min: 5.6 +/- 0.4 cmH2O, +0.168 +/- 0.0.052 g, and 6.4 +/- 0.2, respectively]. Isolated lungs showed increased PMN myeloperoxidase (MPO) activity compared with control in TNF-treated lungs at baseline and 60 min after PMN infusion. Dextran sulfate, dextran, and heparin inhibited the increase in MPO activity. The data indicate that inhibition of PMN sequestration alone is not sufficient for the inhibition of PMN-mediated TNF-induced hydrostatic pulmonary edema and that a charge-dependent mechanism mediates the protective effect of dextran sulfate.     

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.     

Effects of arachidonate on permeability and resistance distribution in canine lungs

In this study, 14 canine lung lobes were isolated and perfused with autologous blood at constant pressure (CP) or constant flow (CF). Pulmonary capillary pressure (Pc) was measured via venous occlusion or simultaneous arterial and venous occlusions. Arterial and venous pressures and blood flow were measured concurrently so that total pulmonary vascular resistance (RT) as well as pre- (Ra) and post- (Rv) capillary resistances could be calculated. In both CP and CF perfused lobes, 5-min arachidonic acid (AA) infusions (0.085 +/- 0.005 to 2.80 +/- 0.16 mg X min-1 X 100 g lung-1) increased RT, Rv, and Pc (P less than 0.05 at the highest dose), while Ra was not significantly altered and Ra/Rv fell (P less than 0.05 at the highest AA dose). In five CP-perfused lobes, the effect of AA infusion on the pulmonary capillary filtration coefficient (Kf,C) was also determined. Neither low-dose AA (0.167 +/- 0.033 mg X min-1 X 100 g-1) nor high-dose AA (1.35 +/- 0.39 mg X min-1 X 100 g-1) altered Kf,C from control values (0.19 +/- 0.02 ml X min-1 X cmH2O-1 X 100 g-1). The hemodynamic response to AA was attenuated by prior administration of indomethacin (n = 2). We conclude that AA infusion in blood-perfused canine lung lobes increased RT and Pc by increasing Rv and that microvascular permeability is unaltered by AA infusion.     

Flow characteristics of open vessels in zone 1 rabbit lungs

To describe the flow characteristics of vessels open in zone 1, we perfused isolated rabbit lungs with Tyrode's solution containing 1% albumin, 4% dextran, and papaverine (0.05 mg/ml). Lungs were expanded by negative pleural pressure (Ppl) of -10, -15, -20, and -25 cmH2O. Pulmonary arterial (Ppa) and venous (Ppv) pressures were varied relative to alveolar pressure (PA = 0) and measured 5-10 mm inside the pleura (i) and outside (o) of the lungs. With Ppa(o) at -2.5 cmH2O, we constructed pressure-flow (P-Q) curves at each Ppl by lowering Ppv(o) until Q reached a maximum, indicating fully developed zone 1 choke flow. Maximum flows were negligible until Ppl fell below -10 cmH2O, then increased rapidly at Ppl of -15 and -20 cmH2O, and at Ppl of -25 cmH2O reached about 15 ml.min-1.kg body wt-1. The Ppv(o) at which flow became nearly constant depended on degree of lung inflation and was 5-8 cmH2O more positive than Ppl. As Ppv(o) was lowered below Ppa(o), Ppv(i) remained equal to Ppv(o) until Ppv(i) became fixed at a pressure 2-3 cmH2O more positive than Ppl. At this point the choke flow was therefore located in veins near the pleural boundary. No evidence of choke flow (only ohmic resistance) was seen in the intrapulmonary segment of the vessels remaining open in zone 1. With Ppv(o) held roughly at Ppl, Q could be stopped by lowering Ppa(o), at which time Ppa(i) was several cmH2O above Ppv(i), showing that intrapulmonary vessel closure had occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Effects of coronary ischemia on lung fluid balance in conscious sheep

It has been suggested that coronary ischemia increases extravascular lung water. To determine whether pulmonary microvascular permeability is increased by coronary ischemia, we measured pulmonary hemodynamics, lung lymph flow (QL), and lymph-to-plasma protein concentration ratio (L/P) in 12 sheep with chronic lung lymph fistulas. Studies were done in 3 groups: in group 1 (n = 7) a marginal branch of the left circumflex artery (Lcx) was occluded, in group 2 (n = 5) left atrial pressure (Pla) was mechanically raised by 10 mmHg, and in group 3 (n = 5) Lcx was occluded and Pla was raised by 10 mmHg. In group 1, coronary occlusion increased QL (4.6 +/- 0.4 to 8.3 +/- 2.6 ml/h) without changes in L/P. In group 2, elevated Pla increased QL (5.1 +/- 1.2 to 10.1 +/- 3.0 ml/h) with decreases in L/P (0.71 +/- 0.02 to 0.61 +/- 0.02). In group 3, coronary occlusion with elevated Pla caused a further increase in QL (5.0 +/- 1.5 to 16.9 +/- 4.6 ml/h) without significant decreases in L/P (0.71 +/- 0.01 to 0.65 +/- 0.06). Lung lymph concentrations of 6-keto-prostaglandin F1 alpha (a degradation product of prostacyclin) increased transiently after coronary occlusion. These results indicate that coronary occlusion can increase transcapillary protein transport in lungs of conscious sheep and simultaneously increase prostacyclin production in the lung.     

Hydraulic conductivity of lung venules determined by split-drop technique

The split-drop method has been used to determine filtration rate per unit surface area in the single pulmonary venule. In isolated perfused lungs of nine dogs, blood flow was stopped at different vascular pressures. By means of a double-micropuncture technique under stereomicroscopy, an oil drop was injected in a subpleural venule. The oil drop was then split with a solution of albumin (5.6 g/100 ml) in Ringer lactate. As the Ringer-albumin solution filtered, the distance between the menisci of the split oil drop (split-drop length) decreased. The split-drop geometry and the rate of change of split-drop length were recorded. The calculated venular filtration rate per unit surface area related linearly with vascular pressure (P less than 0.05). The slope of the line equaled venular hydraulic conductivity, which averaged 2.9 +/- 0.02 x 10(-7) ml/(cm2.s.cmH2O). Hydraulic conductivity is lower in lung than in systemic venules.     

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.     

Longitudinal distribution of vascular compliance in the canine lung

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

Extra-alveolar vessel fluid filtration coefficients in excised and in situ canine lobes

We continuously weighed fully distended excised or in situ canine lobes to estimate the fluid filtration coefficient (Kf) of the arterial and venous extra-alveolar vessels compared with that of the entire pulmonary circulation. Alveolar pressure was held constant at 25 cmH2O after full inflation. In the in situ lobes, the bronchial circulation was interrupted by embolization. Kf was estimated by two methods (Drake and Goldberg). Extra-alveolar vessels were isolated from alveolar vessels by embolizing enough 37- to 74-micron polystyrene beads into the lobar artery or vein to completely stop flow. In excised lobes, Kf's of the entire pulmonary circulation by the Drake and Goldberg methods were 0.122 +/- 0.041 (mean +/- SD) and 0.210 +/- 0.080 ml X min-1 X mmHg-1 X 100 g lung-1, respectively. Embolization was not found to increase the Kf's. The mean Kf's of the arterial extra-alveolar vessels were 0.068 +/- 0.014 (Drake) and 0.069 +/- 0.014 (Goldberg) (24 and 33% of the Kf's for the total pulmonary circulation). The mean Kf's of the venous extra-alveolar vessels were similar [0.046 +/- 0.020 (Drake) and 0.065 +/- 0.036 (Goldberg) or 33 and 35% of the Kf's for the total circulation]. No significant difference was found between the extra-alveolar vessel Kf's of in situ vs. excised lobes. These results suggest that when alveolar pressure, lung volume, and pulmonary vascular pressures are high, approximately one-third of the total fluid filtration comes from each of the three compartments.     

Factors affecting perfusion distribution in canine oleic acid pulmonary edema

Factors affecting perfusion distribution in oleic acid pulmonary edema were examined in 28 anesthetized open-chest dogs. Sixteen had unilobar oleic acid edema produced by left lower lobe pulmonary artery infusion of 0.03 ml/kg of oleic acid, and 12 had the same amount of edema produced by left lower lobe endobronchial instillation of hypotonic plasma. Lobar perfusion (determined from flow probes) and lobar shunt (determined from mixed venous and lobar venous blood) were measured at base line, 1.5 h after edema, and 10 min after 10 cmH2O positive end-expiratory pressure (PEEP). Fourteen dogs (8 oleic acid, 6 plasma) received sodium nitroprusside (11.72 +/- 7.10 micrograms X kg-1 X min-1). Total and lobar shunts increased to the same extent in all animals. Lobar perfusion decreased by 49.8 +/- 4.8% without nitroprusside and 34.0 +/- 3.6% with nitroprusside in the oleic acid group, corresponding values being 40.3 +/- 0.8% and 26.4 +/- 1.7% in the hypotonic plasma group. PEEP returned perfusion and shunt to base line. In oleic acid edema, most of the decreased perfusion results from mechanical effects of the edema, a smaller fraction results from other vascular effects of the oleic acid, and approximately 30% is reversible by nitroprusside. PEEP normalizes the perfusion distribution.     

Interaction of chemical and high vascular pressure injury in isolated canine lung

Because both chemical and mechanical insults to the lung may occur concomitantly with trauma, we hypothesized that the pressure threshold for vascular pressure-induced (mechanical) injury would be decreased after a chemical insult to the lung. Normal isolated canine lung lobes (N, n = 14) and those injured with either airway acid instillation (AAI, n = 18) or intravascular oleic acid (OA, n = 25) were exposed to short (5-min) periods of elevated venous pressure (HiPv) ranging from 19 to 130 cmH2O. Before the HiPv stress, the capillary filtration coefficient (Kf,c) was 0.12 +/- 0.01, 0.27 +/- 0.03, and 0.31 +/- 0.02 ml.min-1.cmH2O-1 x 100 g-1 and the isogravimetric capillary pressure (Pc,i) was 9.2 +/- 0.3, 6.8 +/- 0.5, and 6.5 +/- 0.3 cmH2O in N, AAI, and OA lungs, respectively. However, the pattern of response to HiPv was similar in all groups: Kf,c was no different from the pre-HiPv value when the peak venous pressure (Pv) remained less than 55 cmH2O, but it increased reversibly when peak Pv exceeded 55 cmH2O (P less than 0.05). The reflection coefficient (sigma) for total proteins measured after pressure exposure averaged 0.60 +/- 0.03, 0.32 +/- 0.04, and 0.37 +/- 0.09 for N, AAI, and OA lobes respectively. However, in contrast to the result expected if pore stretching had occurred at high pressure, in all groups the sigma measured during the HiPv stress when Pv exceeded 55 cmH2O was significantly larger than that measured during the recovery period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Permeability of barriers to albumin flux in lungs of sheep resuscitated from hemorrhagic shock

We assessed pulmonary endothelial and epithelial permeability and lung lymph flow in nine adult sheep under base-line conditions and after resuscitation from profound hemorrhagic shock. Animals were mechanically ventilated and maintained on 1% halothane anesthesia while aortic pressure was held at 40 Torr for 3 h. Systemic heparin was not used. After reinfusion of shed blood, sheep recovered from anesthesia and we measured lung lymph flow (QL), lymph-to-plasma concentration ratio for proteins, and time taken to reach half-equilibrium concentration of intravenous tracer albumin in lymph (t1/2). Twenty-four hours after bolus injection of radio-albumin we lavaged subsegments of the right upper lobe and determined fractional equilibration of the tracer in the alveolar luminal-lining layer. In each sheep we had measured these parameters 7 days earlier under base-line conditions. Animals were killed, and the lungs were used for gravimetric determination of extravascular lung water (gravimetric extravascular lung water-to-dry weight ratio) 24 h after resuscitation from shock. Pulmonary endothelial injury after resuscitation was evidenced by marked increase in QL, without fall in lymph-to-plasma ratio. Time taken to reach half-equilibrium concentration fell from 169 +/- 47 (SD) min in base-line studies to 53 +/- 33 min after shock. There was no evidence of lung epithelial injury. Gravimetric extravascular lung water-to-dry weight ratio was significantly increased in these animals killed 24 h after resuscitation (4.94 +/- 0.29) compared with values in our laboratory controls (4.13 +/- 0.09, mean +/- SD). These data demonstrate a loss of lung endothelial integrity in sheep after resuscitation from profound hemorrhagic shock.