Furosemide reduces lung fluid filtration in lambs with lung microvascular injury from air emboli

1989 ◽  
Vol 67 (5) ◽  
pp. 1990-1996 ◽  
Author(s):  
M. E. Berner ◽  
W. G. Teague ◽  
R. G. Scheerer ◽  
R. D. Bland

To study the effects of furosemide on the neonatal pulmonary circulation in the presence of lung injury, we measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma of nine lambs that received furosemide, 2 mg/kg iv, during a continuous 8-h intravenous infusion of air. Air embolism increased pulmonary vascular resistance by 71% and nearly tripled steady-state lung lymph flow, with no change in lymph-to-plasma protein ratio. These findings reflect an increase in lung vascular protein permeability. During sustained lung endothelial injury, diuresis from furosemide led to a rapid reduction in cardiac output (average 29%) and a 2-Torr decrease in left atrial pressure. Diuresis also led to hemoconcentration, with a 15% increase in both plasma and lymph protein concentrations. These changes were associated with a 27% reduction in lung lymph flow. In a second set of studies, we prevented the reduction in left atrial pressure after furosemide by inflating a balloon catheter in the left atrium. Nevertheless, lymph flow decreased by 25%, commensurate with the reduction in cardiac output that occurred after furosemide. In a third series of experiments, we minimized the furosemide-related decrease in cardiac output by opening an external fistula between the carotid artery and jugular vein immediately after injection of furosemide. In these studies, the reduction in lung lymph flow (average 17%) paralleled the smaller (17%) decrease in cardiac output. These results suggest that changes in lung vascular filtration pressure probably do not account for the reduction in lung lymph flow after furosemide in the presence of lung vascular injury.(ABSTRACT TRUNCATED AT 250 WORDS)

1988 ◽  
Vol 254 (3) ◽  
pp. H487-H493
Author(s):  
J. U. Raj ◽  
T. A. Hazinski ◽  
R. D. Bland

To determine the effect of left atrial hypertension on the vascular response to hypoxia in the newborn lung, we measured pulmonary artery and left atrial pressures, lung blood flow and lymph flow, and concentrations of protein in lymph and plasma of 13 lambs that spontaneously breathed air for 2-6 h (control period), followed by 8-11% O2 mixed with 3-5% CO2 and N2 for 2-4 h (experimental period). In eight studies, the lambs were made hypoxic first, after which we elevated their left atrial pressure by 10-12 Torr for 2-3 h. In 10 additional studies, we reversed the sequence by raising left atrial pressure first followed by addition of hypoxia. In lambs with normal left atrial pressure, alveolar hypoxia increased both pulmonary blood flow and lymph flow, with an associated reduction in lymph-to-plasma protein ratio (L/P). When left atrial pressure was increased in the presence of hypoxia, lymph flow increased by a small amount and L/P decreased further. In lambs with preexisting left atrial pressure elevation, addition of alveolar hypoxia increased both blood flow and lymph flow with no significant change in L/P. These results suggest that in newborn lambs with normal left atrial pressure, alveolar hypoxia increases lung lymph flow mainly by increasing microvascular filtration pressure, whereas in lambs with elevated left atrial pressure, hypoxia increases lymph flow by another mechanism, perhaps by increasing the perfused surface area for fluid filtration.


1982 ◽  
Vol 53 (2) ◽  
pp. 432-435 ◽  
Author(s):  
R. P. Simon ◽  
L. L. Bayne ◽  
M. P. Naughton

We compared the effects of elevated left atrial pressure of central nervous system origin (bicuculline-induced seizures) with an identical pulmonary vascular pressure elevation induced in six sheep by inflation of a balloon in the left atrium. The degree and duration of the consequent elevation in pulmonary lymph flow and the alteration in protein movement in the two groups was identical. Alterations in pulmonary fluid and protein flux resulting from generalized seizures can be explained by the pressor response alone; specific brain-lung neural interactions need not be postulated.


1984 ◽  
Vol 56 (4) ◽  
pp. 1083-1089 ◽  
Author(s):  
G. R. Bernard ◽  
J. R. Snapper ◽  
A. A. Hutchison ◽  
K. L. Brigham

To study the mechanism by which infused histamine increases lung fluid and solute exchange, the effects of left atrial pressure elevation (using a Foley catheter positioned at the mitral valve orifice) on lung lymph flow and protein content were studied in the presence and absence of histamine infusion in nine chronically instrumented unanesthetized sheep. In six sheep, histamine infusion (1–3 micrograms X kg-1 X min-1) was begun 2 h before increasing left atrial pressure by 10 and 20 cmH2O for 3 h each. Control experiments were performed on the same sheep to study the effects of left atrial pressure elevation alone and histamine infusion alone. Left atrial pressure elevation in the presence of histamine infusion did not cause a disproportionate increase in lung lymph flow nor was the lymph-to-plasma protein concentration ratio (L/P) different from left atrial pressure elevation alone. This argues against the presence of increased microvascular permeability at the time of these elevations. In three sheep, left atrial pressure was elevated by 20 cmH2O, and then histamine was infused at 2 micrograms X kg-1 X min-1. Histamine infusion caused a transient increase in L/P and a large increase in lymph flow, findings like those we have previously taken to represent an increase in microvascular permeability. However, L/P decreased to values comparable to those seen with elevated left atrial pressure alone. These observations suggest that histamine infusion may have a biphasic effect on lung lymph. There is an early (1–3 h) transient increase in lymph protein clearance that could result from a transient increase in permeability followed by a sustained increase in microvascular surface area. The early response is difficult to interpret because the changes are transient and could be affected by alterations outside the lung.


1986 ◽  
Vol 61 (3) ◽  
pp. 1139-1148 ◽  
Author(s):  
T. A. Hazinski ◽  
R. D. Bland ◽  
T. N. Hansen ◽  
E. G. Sedin ◽  
R. B. Goldberg

To study the influence of plasma protein concentration on fluid balance in the newborn lung, we measured pulmonary arterial and left atrial pressures, lung lymph flow, and concentrations of protein in lymph and plasma of eight lambs, 2–3 wk old, before and after we reduced their plasma protein concentration from 5.8 +/- 0.3 to 3.6 +/- 0.6 g/dl. Each lamb underwent two studies, interrupted by a 3-day period in which we drained protein-rich systemic lymph through a thoracic duct fistula and replaced fluid losses with feedings of a protein-free solution of electrolytes and glucose. Each study consisted of a 2-h control period followed by 4 h of increased lung microvascular pressure produced by inflation of a balloon in the left atrium. Body weight and vascular pressures did not differ significantly during the two studies, but lung lymph flow increased from 2.6 +/- 0.1 ml/h during normoproteinemia to 4.1 +/- 0.1 ml/h during hypoproteinemia. During development of hypoproteinemia, the average difference in protein osmotic pressure between plasma and lymph decreased by 1.6 +/- 2 Torr at normal left atrial pressure and by 4.9 +/- 2.2 Torr at elevated left atrial pressure. When applied to the Starling equation governing microvascular fluid balance, these changes in liquid driving pressure were sufficient to account for the observed increases in lung fluid filtration; reduction of plasma protein concentration did not cause a statistically significant change in calculated filtration coefficient. Protein loss did not influence net protein clearance from the lungs nor did it accentuate the increase in lymph flow associated with left atrial pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)


1988 ◽  
Vol 255 (6) ◽  
pp. H1336-H1341 ◽  
Author(s):  
W. G. Teague ◽  
M. E. Berner ◽  
R. D. Bland

To study the effect of pulmonary perfusion on fluid filtration in the newborn lung, we measured pulmonary vascular pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma of nine healthy, awake lambs, 2–3 wk old, before and during sustained alterations in pulmonary blood flow. A 12% reduction in cardiac output (from partial occlusion of the inferior vena cava) led to a corresponding decrease in lymph flow, consistent with a reduction in net lung fluid filtration. A 20% increase in pulmonary blood flow (from opening an external shunt between the carotid artery and jugular vein) increased lymph flow by approximately 40%, without a significant change in lymph protein concentration. These findings suggest that lung microvascular surface area expanded in response to increased perfusion, with little or no change in filtration pressure. In five lambs, lung microvascular pressure was increased by inflating a balloon catheter in the left atrium to establish full patency of the pulmonary microcirculation. In the presence of left atrial pressure elevation, increased perfusion through the arteriovenous shunt had no significant effect on pulmonary vascular pressures or lymph flow. Thus, in young lambs, modest changes in pulmonary blood flow may affect lung fluid filtration by altering perfused microvascular surface area; this response is inhibited in the presence of left atrial hypertension.


1987 ◽  
Vol 62 (6) ◽  
pp. 2416-2420 ◽  
Author(s):  
R. E. Drake ◽  
S. J. Allen ◽  
J. P. Williams ◽  
G. A. Laine ◽  
J. C. Gabel

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.


1988 ◽  
Vol 255 (5) ◽  
pp. H1149-H1155 ◽  
Author(s):  
F. A. Grimbert ◽  
D. Martin ◽  
J. C. Parker ◽  
A. E. Taylor

We studied the effects of an increase in pulmonary blood flow (PBF) on steady-state lung lymph flow (QL) and protein transport in anesthetized dogs (n = 7) to estimate the effect of vascular recruitment in zone 3 on transvascular filtration. At the end of each experiment, we increased left atrial pressure to 25-30 mmHg using a balloon catheter and obtained a washdown of the lymph protein concentration. PBF was increased with an extracorporeal circuit, which pumped blood from the left to the right atrium, and increases in pulmonary capillary pressure (Pc) were minimized by lowering left atrial pressure. PBF was measured by thermodilution, and Pc was measured by transient analysis of arterial occlusion pressure with a Swan-Ganz catheter. PBF increases averaged 78% with increases ranging from 36 to 118%. Pc increases ranged from 0.5 to 6.3 mmHg, and QL increases averaged 31% with changes ranging from -2 to +138%. We observed a 16% increase in QL for each 1-mmHg increase in Pc during increased PBF, which was comparable to the relationship previously observed after an increased left atrial pressure. Lymph-to-plasma total protein concentration ratios (CL/CP) decreased from 0.71 +/- 0.04 to 0.625 +/- 0.06 during increased PBF. The relationship between CL/CP, QL, and Pc for both increased blood flow and increased left atrial pressure were within the expected range for increased pressure alone. These data suggest that there was minimal vascular recruitment for transvascular filtration in zone 3 when pulmonary blood flow was increased. Microvascular filtration pressure was the main determinant of fluid and protein transvascular filtration under these conditions.


1983 ◽  
Vol 61 (7) ◽  
pp. 714-716
Author(s):  
G. Coates ◽  
L. W. Belbeck ◽  
G. W. Gray

We measured pulmonary artery [Formula: see text] and left atrial [Formula: see text] pressures, lung lymph flow, and lymph/plasma protein concentrations in four adult sheep at a barometric pressure of 380 Torr (1 Torr = 133.322 Pa) for 22 h. Hypobaric hypoxia caused an immediate increase in [Formula: see text] from 20 to 39 Torr. There was no significant change in [Formula: see text], lymph flow, or lymph protein concentrations. We conclude that hypobaric hypoxia does not affect lung fluid or protein exchange in awake adult sheep at rest.


2005 ◽  
Vol 99 (2) ◽  
pp. 556-563 ◽  
Author(s):  
David B. Pearse ◽  
Robert M. Searcy ◽  
Wayne Mitzner ◽  
Solbert Permutt ◽  
J. T. Sylvester

Ventilation (V̇) increases lung lymph flow (Q̇l), but the separate effects of tidal volume (Vt) and frequency (f) and the role of V̇-induced changes in edema formation are poorly understood. An isolated, in situ sheep lung preparation was used to examine these effects. In eight sheep with f = 10 min−1, results obtained during 30-min periods with Vt = 5 or 20 ml/kg were compared with values obtained during bracketed 30-min control periods (Vt = 12.5 ml/kg). Eight other sheep with constant Vt (12.5 ml/kg) were studied at f = 5 or 20 min−1 and compared with f = 10 min−1. Three additional groups of six sheep were perfused for 100 min with control V̇ (10 ml/kg, 10 min−1). Vt was then kept constant or changed to 20 or 3 ml/kg during a second 100-min period. Increases in Vt or f increased Q̇l and vice versa, without corresponding effects on the rate of edema formation. For the same change in V̇, changing Vt had a greater effect on Q̇l than changing f. The change in Q̇l caused by an increase in Vt was significantly greater after the accumulation of interstitial edema. The change in Q̇l caused by a sustained increase in Vt was transient and did not correlate with the rate of edema formation, suggesting that V̇ altered Q̇l through direct mechanical effects on edema-filled compartments and lymphatic vessels rather than through V̇-induced changes in fluid filtration.


1985 ◽  
Vol 58 (4) ◽  
pp. 1314-1318 ◽  
Author(s):  
T. N. Hansen ◽  
A. L. Gest ◽  
S. Landers

The purpose of this study was to examine the effects of inspiratory airway obstruction on lung fluid balance in newborn lambs. We studied seven 2- to 4-wk-old lambs that were sedated with chloral hydrate and allowed to breathe 30–40% O2 spontaneously through an endotracheal tube. We measured lung lymph flow, lymph and plasma protein concentrations, pulmonary arterial and left atrial pressures, mean and phasic pleural pressures and airway pressures, and cardiac output during a 2-h base-line period and then during a 2- to 3-h period of inspiratory airway obstruction produced by partially occluding the inspiratory limb of a nonrebreathing valve attached to the endotracheal tube. During inspiratory airway obstruction, both pleural and airway pressures decreased 5 Torr, whereas pulmonary arterial and left atrial pressures each decreased 4 Torr. As a result, calculated filtration pressure remained unchanged. Inspiratory airway obstruction had no effect on steady-state lung lymph flow or the lymph protein concentration relative to that of plasma. We conclude that in the spontaneously breathing lamb, any decrease in interstitial pressure resulting from inspiratory airway obstruction is offset by a decrease in microvascular hydrostatic pressure so that net fluid filtration remains unchanged.


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