Lung lysosomal enzyme release during hemorrhagic shock and endotoxemia.
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Biomedical subjects
Publications and source records attributed to R H Demling.
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Burns due to hot tar present a difficult management problem because the tar is difficult to remove without inflicting further injury to the underlying burn. We have found the surface active agent polyoxyethylene sorbitan (Tween 80, Sigma, St. Louis, MO) or Polysorbate (Sigma), by itself or in combination with an antibiotic ointment (neomycin sulfate) to be a safe and effective means of tar removal.
Plasma and lung lymph beta-glucuronidase and aryl sulfatase A specific activity were measured before and for 48 hours after a 50% full-thickness burn in the adult sheep. We noted a significant increase in plasma activity of both enzymes with maximum increase occurring 3 hours postburn, with levels returning toward baseline at 48 hours. Increase in plasma activity correlated in time course with increases in pulmonary vascular resistance. Lung lymph specific activity increased to levels identical to that in plasma but the time course lagged behind by 1 to 3 hours.
The measurement of pulmonary vascular pressure and plasma oncotic pressure (pi p) is reported to be useful for predicting excess fluid transport across the pulmonary microcirculation in the critically ill. However, interpretation of change in these forces must take into consideration the compensatory changes in the other Starling forces, particularly interstitial oncotic pressure (pi i) and the permeability characteristics of the membrane. We calculated pulmonary microvascular pressure Pmv, pi p, and pi i in unanesthetized sheep with lung lymph fistulae. We altered Pmv by fluid loading and pi p by producing a severe hypoproteinemia after hemorrhagic shock and altered the membrane with endotoxin. We compared these with changes in the pulmonary transvascular fluid filtration rate (Qf). We found Pmv correlated very well with Qf during volume loading and during the post-shock hypoproteinemic state. pi i decreased in response to decreases in pi p, producing a relatively constant oncotic gradient (pi p-pi i). pi p then correlated very poorly with Qf when hypoproteinemia was present. There was essentially no correlation between any of the pressures and Qf after the severe permeability change produced by endotoxin.
The ability of macrophages of phagocytize particulate matter is largely dependent on fibronectin, a nonspecific opsonin found in plasma. Fibronectin depletion, resulting in reticuloendothelial system (RES) depression, occurs following a variety of physical insults. RES depression may contribute to postinjury sequelae such as respiratory distress syndrome and septicemia. Fibronectin concentration was measured in the plasma of sheep with chronic lung lymph fistulas subjected to controlled thermal injury. Fibronectin levels were significantly (p < 0.05) decreased at 4, 24, 48, and 72 hours following burning. Fibronectin concentration decreased in parallel with serum albumin concentration; serum globulin concentrations did not decrease. Fibronectin concentration had an inverse relationship to lung lymph flow, a reflection of pulmonary transvascular fluid filtration rate. The role of fibronectin in the pathogenesis of postinjury respiratory distress syndrome deserves further exploration.
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We wanted to compare the systemic and pulmonary vascular response to Escherichia coli endotoxin with changes in lysosomal enzyme activity in plasma and lung lymph in the unanesthetized sheep with a lung lymph fistula. We wanted to determine whether lysosomal enzyme activity (LE) was a reliable marker of injury and LE increase appears to be different for the two systems.
The colloid osmotic pressure of plasma, pi p, and lung lymph pi i, in the adult sheep was measured with a membrane osmometer and calculated from the protein content using the Landis and Pappenheimer equation. Measured (M) plasma oncotic pressure was 6 mm Hg lower than calculated (C), for normal sheep plasma. The difference between (M) and (C) decreased as protein content decreased. The (M) lymph value, considered to be equal to interstitial fluid, was only 1 mm Hg lower than (C) for normal lymph. This resulted in a difference between the calculated and measured oncotic gradient (pi p-pi i) of nearly 5 mm Hg. This difference decreased as protein content decreased in plasma and lymph. The difference between measured and calculated values may in part be explained by the differences in A/G ratio between human and sheep plasma and between sheep plasma and lymph. Measured oncotic pressure in plasma and lymph after severe hemorrhagic and endotoxic shock did not differ significantly from that in the normal animal.
We compared the response of the pulmonary microcirculation to fluid overload before and 24 hours after hemorrhagic shock, resuscitated with either blood or crystalloid, to determine whether vascular permeability was altered, making the lung more susceptable to fluid overload after shock and whether this response differed depending on the type of resuscitation fluid. Fourteen unanesthetized sheep with chronic lung lymph fistula were given a fluid challenge (one half of blood volume) before and 24 hours after hemorrhagic shock. Seven sheep were resuscitated after whock with shed blood and seven sheep were resuscitated with Ringer's lactate alone equal to 2.5 times the amount of shed blood. Pulmonary vascular pressures and lung lymph flow Ql were at baseline in both groups 24 hours after resuscitation except for the decreased plasma oncotic pressure pi p in the crystalloid group. Interstitial oncotic pressure, pi i was also lowered in this group such that the gradient (pi p-pi i) remained at baseline. In the blood group, pulmonary vascular pressures and QL increased transiently after fluid loading before and after shock with the mean time for QL to return to baseline being 5.5 and 5.9 hours for the preshock and postshock periods, respectively. In the crystalloid group, fluid loading after shock produced an increase in pulmonary vascular pressures resulting in a significant increase in QL over the preshock fluid response with the mean time for QL to return to baseline being 10.1 hours. However, changes in the value of (pi p-pi i) were identical to those seen before shock. Therefore we noted that 24 hours after shock, lung permeability was not significantly altered but crystalloid resuscitation did make the lung more susceptible to volume overload.
Fluid and protein flow across the pulmonary microcirculation was measured during hemorrhagic shock resuscitation and recovery using either blood or crystalloid as the resuscitation fluid. Fluid filtration rate (Qf) and protein permeability were measured using, as reliable indicators, lung lymph flow and lymph protein content in the unanesthetized sheep with chronic lung lymph fistula. During shock, Qf was maintained, probably because of an increase in pulmonary venous resistance. During resuscitation Qf was significantly increased, but no increase in protein permeability was noted. This increase in Qf was not affected by the type of resuscitation fluid, as the decrease in plasma oncotic pressure with crystalloid was compensated for by a decrease in plasma oncotic pressure with crystalloid was compensated for by a decrease in the interstitial oncotic pressure. Crystalloid resuscitation did, however, increase the Qf response to a fluid challenge in the recovery period, whereas blood resuscitation did not.
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The accumulation of excess lung water is a major concern after the infusion of large amounts of crystalloid solution. The parameters used to monitor total body and lung water balance include changes in body weight, and the measurement of pulmonary vascular and plasma colloid osmotic pressures. We studied the reliability of these parameters in predicting lung water during severe fluid overload in nephrectomized sheep. We found that the normal lung appeared resistant to excess fluid accumulation, particularly when compared to the splanchnic circulation. Body weight change was an unreliable index of lung water with a correlation coefficient of 0.43. Pulmonary vascular pressures were the best index (r = 0.83) with lung water accumulating rapidly after capillary pressure exceeded 30 cm H2O. The difference between pulmonary capillary pressure and plasma colloid osmotic pressure was not as reliable (r = 0.72) as was capillary pressure alone.
Massive wound edema after a burn may impair healing and help to convert partial to full-thickness injury. Cold treatment (usually by immersion) has been reported to decrease wound edema and is useful in first-aid treatment of burns. Reliable quantitative data have been lacking and frequently a superficial burn has been studied. Since cold by decreasing peripheral blood flow could actually be harmful to a deep burn, especially if applied late, we measured the effect of cold immediately and 2 minutes postburn on edema formation and resorption in a deep second-degree burn in sheep hindlimbs. We used Dichromatic Absorptiometry, a noninvasive, reliable method for measuring tissue fluid, to quantitate edema. Immediate application of cold by immersion in 15 degrees C saline for 30 minutes reduced the edema of a deep second-degree burn and did not impair resorption rate compared with control limbs, fluid content returning to baseline after 1 week. Cold treatment beginning 2 minutes after the burn did not decrease edema formation and did impair resorption. Fifteen per cent of the edema fluid was still present 1 week postburn, suggesting further injury to the burn wound vasculature with use of cold immersion 2 minutes postburn.
We studied the effect of hemorrhagic shock, resuscitation, and recovery on the pulmonary microcirculation. We used lung lymph flow (QL) and lymph-to-plasma protein ratio as sensitive indices of transvascular fluid filtration rate and protein permeability. We measured pulmonary vascular pressures, cardiac output, blood gases, lymph flow, and lymph and plasma proteins before and during a 2-h period of shock, a 3-h period of resuscitation, and a 72-h period of recovery, in nine unanesthetized sheep with chronic lung lymph fistula. We found a 30% decrease in QL during early shock as animals were bled into bags containing an acetate citrate dextrose solution until aortic pressure was 50 Torr. QL gradually increased to or exceeded base line in five of nine animals during late shock as pulmonary vascula resistance increased by 250%. During the 3-h resuscitation period, mean QL increased by 110%, with the lymph-to-plasma protein ratio being significantly decreased, indicating no protein permeability change. In five of nine studies, lymph became visible bloody. The increased QL and lymph RBCs were felt to be secondary to an elevation in microvascular pressure. During the recovery period, pressures and QL returned to base line.
Our purpose was to determine the reliability of the currently used measurements of pulmonary vascular hydrostatic and oncotic pressures in monitoring pulmonary water after a major burn. The flow of pulmonary lymph, a reliable indicator of the rate of filtration of pulmonary transvascular fluid (Qf), was measured before and for 72 hours after a third-degree burn over 40 to 55 percent of the total body surface in sheep. Changes in Qf were correlated with measured changes in pulmonary microvascular (Pmv), plasma colloid osmotic pressure (pi p), and interstitial colloid osmotic pressure (pi i), as measured in the pulmonary lymph. The periods from 0 to 24 hours (resuscitation), from 24 to 48 hours (early mobilization of fluid), and from 48 to 72 hours (early recovery) were compared with baseline. Regression equations and correlation coefficients for Qf vs Pmv, Qf vs Pmv minus pi p, and Qf vs Pmv minus (pi p -ph i), the oncotic gradient, were calculated. There were significant differences in slopes between the periods of time, with all three comparisons indicating that the response of the microcirculation to the same changes in pressure was different in each of the periods. The correlation between Qf and the comparisons of pressures was clearly best in the period from 48 to 72 hours. The comparison of Pmv minus pi p was not better than Pmv alone, while the comparison of Pmv minus the gradient (pi p -- pi i) was significantly better than either of the other comparisons in predicting Qf.
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