The change of extra vascular lung water volume in patients undergoing surgery for esophageal cancer

In 27 operations on esophageal cancer, extra vascular lung water (EVLW) was used as pre- and postoperative parameter in the control of the respiratory function. The cases were divided into 2 groups. Group I consisted of 6 cases with pulmonary complications and group II, 21 cases without them. The changes of EVLW and the circulatory and respiratory parameters were compared between 2 groups. Preoperative EVLWs were 5.56 +/- 0.67 ml/kg in group I and 5.76 +/- 0.41 ml/kg in group II. The immediate postoperative EVLWs were 6.65 +/- 1.90 ml/kg in group I and 4.86 +/- 0.31 ml/kg in group II, but the difference was insignificant. Beyond the 12th hour of the postoperative period there was no significant difference in the EVLW levels of groups I and II. In group II the immediate postoperative EVLW was significantly less than the preoperative value. Only 2 cases had pulmonary edema. The immediate postoperative EVLWs of these patients were extremely elevated as compared with the preoperative value. Many reports said EVLW correlated with colloid osmotic pressure-pulmonary wedge pressure gradient or PaO2, but in our cases EVLW did not correlate with any parameter. From these results, it was assumed EVLW was the good parameter for early diagnosis and management of pulmonary complication after surgery for esophageal cancer.     

Evaluation of the thermal technic for the quantitative measurement of extravascular lung water

To evaluate the accuracy of the method, sequential measurements (n = 159) of extravascular lung water (EVLW) using the thermo-dye double-indicator dilution technique were performed in 22 critically surgical ill patients. Radiographic grading of lung water content served as clinical standard. Normal mean EVLW defined radiographically without evidence of pulmonary edema was 4.8 +/- 1.1 ml/kg. Early interstitial fluid accumulation was quite accurately detected with 6.9 +/- 2.1 ml/kg EVLW (p less than 0.001 vs normal lung water content). The mean EVLW present with definitive interstitial and alveolar edema was 11.5 +/- 3.8 ml/kg and 19.1 +/- 4.5 ml/kg, respectively. Despite some objections to the method (diffusion limitation of the thermal indicator, uneven regional lung perfusion), this technique for measuring EVLW reliably assesses the degree of pulmonary edema. Even when properly performed, chest roentgenograms only confirm gross changes in the lung water content.     

Preoperative normvolemic hemodilution in heart surgery. Pulmonary changes with the use of new technics

Interest in preoperative hemodilution (HD) has intensified perceptibly again, because of the increasing risk of adverse reactions to donor blood. However, in coronary surgery patients the use of HD is still the subject of controversy, as it may possibly influence organ function and especially lung water content. New techniques, including membrane oxygenation, extracorporeal circulation (ECC) with only "partial" bypass due to 2-stage cannulation, and hemoconcentration with cell separators, have significantly modified patient management in the field of cardiac surgery. Therefore, the influence of moderate hemodilution (12 ml/kg) on extravascular lung water (EVLW) was investigated under these conditions in 45 patients with coronary artery disease. Volume replacement was performed either with hydroxyethyl starch solution (HD-HES group, n = 15, ratio of replacement 1:1) or with Ringer's lactate (HD-RL-group, n = 15, ratio 2.5:1); 15 patients not subjected to HD served as controls. ECC was carried out with membrane oxygenators only in partial bypass. Both during and after ECC, blood was concentrated by means of a cell-saving system allowing separation and reinfusion of the red cells while the plasma is discarded. EVLW was measured using a double-indicator dilution technique with indocyanine green. Starting from comparable baseline values, EVLW was not significantly changed by hemodilution. After ECC, however, the HD-RL group showed a significant increase in lung water content (means: +2.49 ml/kg equal 42.6%), whereas this was not significantly changed in the other groups. By 5 h after ECC, the lung water content had returned to baseline values and no more differences could be observed between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of arachidonic acid metabolites in oleic acid induced pulmonary injury in a canine model. Effect of ketoconazole (thromboxane synthetase inhibitor)

This study was designed to investigate the effects of ketoconazole, a thromboxane synthetase inhibitor, on pulmonary and systemic hemodynamics and pulmonary function in experimental respiratory distress syndrome. Pulmonary artery infusion of oleic acid (PAIOA), 0.1 ml/kg, was used to cause lung injury. Ten dogs were randomized into two groups (Gps): Gp I (n = 5) acted as control, whereas Gp II (n = 5) were treated with IV ketoconazole (2.5 mg/kg bolus then 10 mg/kg/hour for 2.5 hours). Hemodynamics, extravascular lung water (EVLW), serum levels of PGE2, and TxB2 were obtained at baseline (BL) and at 30-minute intervals for 2.5 hours (T30-T150). After 30 minutes of PAIOA the mean arterial pressure (MAP) decreased significantly in both Gps (131 +/- 17 vs. 88 +/- 9 mmHg Gp 1, 119 +/- 9 vs. 79 +/- 8 mmHg Gp II, P less than 0.05); however, while MAP returned to BL values in Gp II, it remained significantly lower throughout the experimental interval in Gp I. Mean pulmonary artery pressure (MAP) was not significantly affected by PAIOA in either Gp, while pulmonary vascular resistance increased significantly from BL at T120 in Gp II. Pulmonary function measured by partial pressure of arterial O2 (PaO2) and extravascular lung water (EVLW) were significantly affected by PAIOA. There was a significant decrease in PaO2 (66 +/- 6 vs. 96 +/- 8 mmHg, Gp I and 60 +/- 7 vs. 100 +/- 6 mmHg, Gp II) as well as an increase in EVLW (604 +/- 61 vs. 135 +/- 9 ml, Gp I and 641 +/- 110 vs. 117 +/- 18 ml, Gp II) in both Gps.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurogenic pulmonary edema in the acute stage of hemorrhagic cerebrovascular disease

Extravascular lung water (EVLW) was measured by the double-indicator dilution method in 25 patients with hemorrhagic cerebrovascular diseases. EVLW had a significantly positive correlation with both alveolar-arterial oxygen difference (AaDO2) and intrapulmonary shunt. The value of EVLW in the acute stage in 15 patients with increased AaDO2 more than 20 mm Hg was 7.8 +/- 2.2 ml/kg and that in the chronic stage 4 weeks after onset significantly decreased to 4.6 +/- 0.7 ml/kg (P less than 0.001). The value of EVLW in the acute stage in 10 patients with normal AaDO2 less than 20 mm Hg was 4.7 +/- 1.1 ml/kg and that in the chronic stage 4 weeks after onset was 4.5 +/- 0.2 ml/kg. There was no significant difference between them. Pulmonary arterial blood pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac index, systemic vascular resistance index, and pulmonary vascular resistance index in the acute stage in the 25 patients were all within the normal range. Three patients with neurogenic pulmonary edema had markedly increased EVLW without abnormalities in pulmonary arterial blood pressure, pulmonary capillary wedge pressure, central venous pressure, cardiac index, systemic vascular resistance index, and pulmonary vascular resistance index. From these facts, the main cause of the increase in EVLW cannot be explained by left ventricular failure, but can be explained by high permeability pulmonary edema.     

Effects of pleural fluid and positive end-expiratory pressure on the measurement of extravascular lung water by the double-indicator dilution technique

The reliability of the double-indicator dilution technique (dye/cold) for measuring extravascular lung water (EVLW) has been studied in lung-healthy dogs after pleural fluid injection of saline (up to 20 ml/kg) during mechanical ventilation at zero and 10 cmH2O (1.0 kPa) end-expiratory pressure (ZEEP and PEEP, respectively). Pleural fluid injection had no effect on EVLW at either ZEEP or PEEP. PEEP induced changes in cardiac output, and reduced both the intravascular (dye) and the thermal indicator volumes, but with no effect on the calculated EVLW. It is concluded that pleural fluid up to 20 ml/kg and ventilation with PEEP of 10 cmH2O (1.0 kPa) do not affect the reliability of the double-indicator dilution technique for measuring extravascular lung water in the dog.     

Studies on pre- and postoperative extravascular lung water changes in patients with esophageal cancer

Pre- and postoperative extravascular lung water (EVLW) changes in a series of twenty patients with esophageal cancer were studied using thermal-dye double-indicator dilution method. Preoperative EVLW was 8.2 +/- 2.3 ml/kg (M +/- SD), being greater as compared to the normal range of EVLW. The pattern of postoperative EVLW changes varied between patients and changes could not be predicted by the conventional examinations including chest X-ray, determination of pulmonary hemodynamics and blood gas analysis. Analysing the relationship between the changes in COP-PWP gradient and EVLW, COP-PWP gradient decreased on the first postoperative day regardless of the EVLW changes. With regard to the changes for the 2nd to the 3rd day or for the 3rd to the 4th day, however, the patients with elevating EVLW showed falling COP-PWP gradient, whereas the patients having decreasing EVLW had an increase in COP-PWP gradient. Especially, the patients in which EVLW had increased during the 3rd to the 4th day showed a remarkable rise of PWP possibly due to depressed left ventricular function. It is considered that the EVLW increase on the first postoperative day is attributable to an alteration of the permeability characteristics of alveolar capillary but that the increase in the 3rd to 4th day is simply due to an elevated hydrostatic pressure. This suggests that there are two different kinds of mechanism involving in the production of wet lung following esophageal cancer surgery.     

Fluid challenge in patients at risk for fluid loading-induced pulmonary edema

BACKGROUND: This study evaluated the effects of protocol-guided fluid loading on extravascular lung water (EVLW) and hemodynamics in a group of patients at high risk for volume expansion-induced pulmonary and systemic edema. METHODS: Nine acutely admitted septic patients with acute lung injury (ALI) were prospectively studied. In addition to sepsis and ALI, the following criteria indicating increased risk for edema formation had to be fulfilled: increased vascular permeability defined as microalbuminuria greater than fivefold normal and hypoalbuminemia < 30 g l(-1). Two hundred-ml boluses of a 10% hydroxyethyl starch (HES) was titrated to obtain best filling pressure/stroke volume relation. Extravascular lung water and intrathoracic blood volume (ITBV) were measured using a transpulmonary double-indicator dilution technique. Baseline data were compared with data at the end of fluid loading and 3 h postchallenge. RESULTS: At study entry the mean EVLW was 13 ml kg(-1), and the mean EVLW/ITBV ratio (indicator of pulmonary permeability) was 0.72 (normal range 0.20-0.30). To attain optimal preload/stroke volume relation 633 +/- 240 ml of HES was needed. Fluid loading significantly increased preload (CVP, PAOP and ITBV), and stroke volume. Effective pulmonary capillary pressure (Pcap) rose only slightly. As a result, the Pcap-PAOP gradient decreased. Despite increased cardiac output, EVLW did not change by plasma expansion. CONCLUSION: In this selected group of at-risk patients, the optimization of cardiac output guided by the concept of best individual filling pressure/stroke volume relationship did not worsen permeability pulmonary edema.     

Pulmonary edema: reversal by ultrafiltration

Ultrafiltration, the process by which plasma water is removed from the blood was utilized to determine its effect on lowering lung water in pulmonary edema produced by fluid overload, steam inhalation, and endotoxin. Lung water was measured by the thermal-dye indicator dilution technique which correlated well with lung water measured gravimetrically over a wide range (r = 0.95). Edema was produced by fluid overload in five mongrel dogs (Group I), by steam inhalation (Group II), and by endotoxin (Group III). Extravascular lung water (EVLW) rose significantly (P = less than 0.05) from control levels with the production of the edematous states (Group I: 8.0 ml/kg (mean) +/- 1.9 (SD) to 13.1 +/- 1.9); (Group II: 8.1 +/- 1.0 to 10.7 +/- 0.7); (Group III: 7.4 +/- 0.9 to 10.3 +/- 1.2). EVLW then fell significantly (P = less than 0.05) after ultrafiltration in all three groups (Group I: 8.9 +/- 2.4; Group II: 7.8 +/- 1.9; Group III: 7.7 +/- 1.4). Ultrafiltration was effective in reversing pulmonary edema and may have clinical application when excess lung water interferes with cardiac or pulmonary function.     

Resuscitation and extravascular lung fluid in cardiac surgery

Cardiovascular arrest may be followed by severe respiratory insufficiency due to an increase in the pressure in the pulmonary vascular system, an alteration in capillary permeability, or both. Extracorporeal circulation (ECC), on the other hand, can lead to a change in capillary integrity ('capillary leakage') caused by the unphysiologic perfusion patterns and/or activation of various mediator systems. Pulmonary hyperhydration (increased extravascular lung water [EVLW]) seems to be the most important factor limiting pulmonary function in this situation. This retrospective study was designed to investigate the influence of resuscitation in the period before ECC on pulmonary EVLW thereafter. Eight coronary surgery patients who had to be resuscitated in the period before the start of ECC due to cardiocirculatory arrest were compared to 8 patients without resuscitation selected randomly (control group). There were no differences between the two groups with regard to age, catheterization data, and ECC conditions. All patients underwent identical monitoring, including estimation of EVLW. Lung water measurement was performed by the thermal dye technique with indocyanine green (= non-diffusible indicator) dissolved in ice-cold dextrose (= diffusible indicator) and a bedside microprocessor before resusciation and after ECC (15 min, 45 min, 5h). Simultaneously, hemodynamics and parameters of pulmonary gas exchange were monitored. Baseline values of EVLW were comparable in both groups. After ECC a transient increase in EVLW could be demonstrated in the controls, indicating an altered fluid flux even in 'uncomplicated' courses; 5 h after ECC lung water content had again reached baseline values. In contrast, there was a significant increase in EVLW in the 'complicated group' immediately after ECC (+2.60 ml/kg) and 5 h after ECC (+1.38 ml/kg); in consequence, the paO2 was significantly decreased (-180 mmHg) while Qs/Qt was increased (+6.79%). It is concluded that the combination of two factors that potentially damage pulmonary tissue and increase lung water content (reanimation due to circulatory arrest and extracorporeal circulation) lead to a significant increase in extravascular lung water combined with a deterioration of pulmonary function, resulting in severe respiratory failure.     

Procalcitonin (PCT) in cardiac surgery: diagnostic value in systemic inflammatory response syndrome (SIRS), sepsis and after heart transplantation (HTX)

PURPOSE: Since it is of great importance to distinguish between a systemic inflammatory response syndrome (SIRS) and an infection caused by microbes especially after heart transplantation (HTX), we examined patients following heart surgery by determining procalcitonin (PCT), because PCT is said to be secreted only in patients with microbial infections. METHODS: Sixty patients undergoing coronary artery bypass grafting (CABG) and 14 patients after heart transplantation were included in this prospective study. In the CABG group we had 30 patients without any postoperative complications (group A). Furthermore we took samples of 30 patients who suffered postoperatively from a sepsis (group B, n=15) or a systemic inflammatory response syndrome (C, n=15). In addition we measured the PCT-levels in 65 blood samples of 14 patients after heart transplantation (Group I: rejection > IIa, II: viral infection (CMV), III: bacterial/fungal infection, IV: controls). RESULTS: In all patients of group A the pre- and intraoperative PCT-values and the measurement at arrival on intensive care unit (ICU) were less than 0.2 ng/ml. On the second postoperative day the PCT-value was 0.33+/-0.15 ng/ml in the control group. At the same time it was 19.6+/-6.2 ng/ml in sepsis and 0.7+/-0.4 ng/ml in systemic inflammatory response syndrome patients (P<0.05). In transplanted patients we could find the following PCT-values: Gr.I: 0.18+/-0.06 II: 0.30+/-0.09 III: 1.63+/-1.16 IV: 0.21+/-0.09 ng/ml (P<0.05 comparing group III with I, II and IV). CONCLUSIONS: These results show that extracorporeal circulation (ECC) and systemic inflammatory response syndrome do not initiate a PCT-secretion. Septic conditions cause a significant increase of PCT. In addition, PCT is a reliable indicator concerning the essential differentiation of bacterial or fungal--not viral--infection and rejection after heart transplantation.     

Does the technique of cardiopulmonary bypass affect lung water content?

Several efforts have been made to improve the technique of cardiopulmonary bypass (CPB), including the use of pulsatile flow and the modification of cannulation technique. The present study focused upon extravascular lung water (EVLW) in 60 aortocoronary bypass patients subjected to four different perfusion techniques during CPB: group 1 (n = 15): non-pulsatile flow and standard cannulation; group 2 (n = 15); pulsatile flow and standard cannulation; group 3 (n = 15): nonpulsatile flow and monoatrial cannulation (i.e., always "partial" bypass during CPB); group 4 (n = 15): pulsatile flow and monoatrial cannulation. EVLW content was measured using the double-indicator dilution technique with indocyanine green; in addition, various hemodynamic and laboratory variables were measured. Lung water content rose above normal values (mean: 5.79 +/- 0.33 ml/kg) only in the groups submitted to the standard cannulation technique, irrespective of whether the perfusion flow was pulsatile or not (group 1: + 27.4%; group 2: + 25.5%). Pulmonary gas exchange, too, was compromised only in these patients (PaO2 in group 1 -19% and in group 2 -17%; Qs/Qt in group 1 + 36 rel. % and in group 2 + 29 rel. %), whereas all patients with monoatrial cannulation and partial bypass throughout the CPB period showed no rise in EVLW content or Qs/Qt and no drop in PaO2. From the results of this study we conclude that pulsatile perfusion during open heart surgical procedure has no advantages in regard to lung water content. Monoatrial cannulation with partial bypass at all times during CPB, however, seems to be beneficial, probably owing to the maintenance of pulmonary circulation during the bypass period.     

Measurement of extravascular lung water in sheep during colloid and crystalloid resuscitation from smoke inhalation

The pathophysiology of pulmonary inhalation injury, a major cause of morbidity and mortality from fires, is poorly understood. To examine the effects of colloid and crystalloid resuscitation on extravascular lung water (EVLW) during a standard smoke inhalation injury, we subjected 12 sheep to 8 minutes of cool pine smoke inhalation. The animals were then resuscitated to a pulmonary capillary wedge pressure (PCWP) of 10 +/- 1.5 mm Hg with either lactated Ringer's solution or plasma protein derivative. EVLW, cardiac output, vascular resistance, colloid oncotic pressure (COP), arterial and pulmonary artery pressures, PCWP, and blood gases were monitored during 4 hours of resuscitation. In colloid-treated animals, EVLW increased from 8.3 +/- 1.2 to 11.1 +/- 0.9 ml/kg with injury; it increased only to 12.5 +/- 1.3 ml/kg during resuscitation. In crystalloid-treated animals, EVLW increased from 8.0 +/- 1.0 to 10.3 +/- 0.8 ml/kg with injury and further increased to 17.4 +/- 1.6 ml/kg during resuscitation, a level significantly higher than that in the colloid group (P less than 0.05). The increases in EVLW were associated with progressive hypoxia, which was worse in the crystalloid group. In the crystalloid group, COP decreased from 27.3 +/- 0.9 to 14.2 +/- 0.4 mm Hg and intravascular driving force (COP-PCWP) dropped from 17.6 to 3.26 +/- 1.5 mm Hg; COP and COP-PCWP were maintained in the colloid group. These data demonstrate that supporting serum COP minimizes the increase in EVLW with smoke inhalation injury and suggests that smoke inhalation does not lead to a dramatic increase in alveolar capillary membrane permeability to protein.     

Manipulation of tissue forces in treating the adult respiratory distress syndrome

In 16 anesthetized dogs, low-pressure pulmonary edema was induced by the intravenous infusion of oleic acid (0.02 mL/kg). One group of four animals served as controls. In the remaining 12 animals, the pulmonary capillary wedge pressure (Pcwp) was lowered in an effort to decrease the accumulation of extravascular lung water (EVLW). In eight dogs, the EVLW value decreased as measured by the thermal green dye, double-indicator method. The low Pcwp was maintained until the EVLW reached a minimum. In four dogs, reduction of the Pcwp did not decrease the accumulation of EVLW but did reduce the rate of accumulation. In animals in which the EVLW reached a minimum, restoration of Pcwp to baseline values did not increase edema, while the control animals continued to deteriorate. Presumably, changes in tissue and lymphatic dynamics compensated for the increased capillary permeability.     

Measurement of dynamic lung fluid balance in the mechanically ventilated dog. Theory and results

An expression (LN) is presented for the net fluid leakage from the intravascular to the extravascular space in the lung. It is based on a new dog model and is the sum of rate of change in extravascular lung water content (EVLW), thoracic lymph flow, and pleural fluid formation. The rate of change of EVLW (delta EVLW) in ml/kg/h was calculated from repeated measurements of EVLW with a double-indicator dilution technique (dye/cold) and corrected according to the relation between EVLW measured by this technique and gravimetry. LN was studied in lung-healthy mechanically ventilated dogs during a prolonged period of mechanical ventilation with and without the application of a positive end-expiratory pressure of 10 cmH2O (1.0 kPa). During mechanical ventilation, LN was found to be 0.3 ml/kg/h in the basal condition, increasing to 0.5 ml/kg/h (P less than 0.01) after a mean period of 7 h. After the application of a positive end-expiratory pressure (PEEP) of 10 cmH2O (1 kPa) for 0.5-2 h, LN was found to increase significantly, from a mean of 0.3 ml/kg/h to 0.9 ml/kg/h (P less than 0.01). We conclude that LN is a useful quantitative expression in experimental studies on lung fluid balance.     

Sildenafil extends survival and graft function in a large animal lung transplantation model.

OBJECTIVE: Restoring intracellular cGMP and inducing NO-synthesis attenuates ischemia-associated early pulmonary allograft dysfunction. Phosphodiesterase-5 (PDE), predominantly expressed in lung tissue, plays a pivotal role in modulating the cGMP/NO-synthase pathway in endothelial and epithelial cells. In this study, we evaluate the effect of employing sildenafil (Viagra), a specific inhibitor of PDE-5, to counteract ischemia/reperfusion (I/R) injury in a single lung transplantation model of extended ischemia. METHODS: Donor animals (weight matched outbred pigs, 28-35 kg) in the treatment group (I) (n=5) were injected with 0.7 mg sildenafil/kg into the pulmonary artery (PA) prior to inflow occlusion. For perfusion, Perfadex, containing 0.7 mg sildenafil/l was used, and the graft stored at 1 degrees C in the perfusion solution. After 24h ischemia, unilateral left lung transplantation was performed. Starting at reperfusion, group I received continuous sildenafil (0.7 mg sildenafil/kg), over 6h. Except for the sildenafil application, the control group (II) (n=4) was treated identically (PGE1 was injected into the PA). One hour after reperfusion, the right main bronchus (MB) and right PA were occluded. Over the next 5h, cardiopulmonary parameters (systemic atrial, PA, central venous, left atrial pressure, pCO(2), pO(2)) were measured, including extravascular lung water (EVLW). Thiobarbituric acid-reactive substance assay (TBARS) and myeloperoxidase (MPO) analysis from lung tissue were run. RESULTS: All recipients of group I survived the 6-h reperfusion period; in contrast, all control animals died within 1-2h after occlusion of the right side. In comparison to a marked rise in pulmonary vascular resistance (PVR) in group II (>1000 dynescm(-5)), PVR in group I remained stable, moderately elevated from baseline (baseline: 150-180 dynescm(-5) vs endpoint: 1000 dynescm(-5)). EVLW in group I did not increase during reperfusion (baseline: 6.75+/-1.4 mg/kg vs endpoint: 6.7+/-1.0mg/kg), in contrast to group II, where pulmonary edema at 2-h reperfusion preceded terminal graft failure (group I: 9.7+/-0.1mg/kg vs group II: 6.48+/-1.8 mg/kg). Tissue reactive free radicals at endpoint measurement in group I did not differ significantly from native tissue. Yet, when compared to specimen taken from group II at time of terminal graft failure, a significant increase in free radicals was noted (group I: 13.8+/-1.6 pmol/g vs group II: 18.5+/-3.0 pmol/g, p<0.05). CONCLUSION: Sildenafil treatment prevents terminal early graft failure, allowing lung transplantation after 24-h ischemia time. Reperfusion edema was strikingly diminished, preserving pulmonary structural and functional integrity while prolonging graft ischemia time. Employing the established PDE-5 inhibitor sildenafil during lung perfusion, storage, and implantation, ischemic tolerance may be extended and early graft function improved.     

Furosemide during sustained left atrial hypertension in functionally anephric dogs: intravascular and extravascular pulmonary fluid volumes. V

The response of intravascular (PBV) and extravascular (EVLW) pulmonary fluid volume was examined using double-indicator techniques (thermal-green dye) in 11 open-chest anesthetized dogs during the production of sustained left atrial (LA) hypertension by a LA balloon over a period of 195 min. In 6 of these animals data were also acquired after the intravenous administration of furosemide (1 mg/kg). The renal effects of the diuretic were blocked by tying off the ureters and the vascular supply of both kidneys. Left atrial pressure (N = 11) was abruptly increased from 2.2 +/- 2.1 mm Hg to 30.2 +/- 4.0 mm Hg (P less than 0.01) and maintained at that level for 120 min. Data were obtained prior to pressure elevation, immediately upon pressure elevation, and then every 60 min for a total of 120 min. At that point EVLW had increased (8.1 +/- 0.8 cc/kg at control to 21.7 +/- 2.0 cc/kg at 120 min, P less than 0.001), as had PBV (6.2 +/- 2.1 cc/kg to 9.1 +/- 3.1 cc/kg P less than 0.01). After furosemide injection (N = 6), LA pressure declined (mean peak reduction of approximately 6 mm Hg at 60-75 min, P less than 0.01), aortic and pulmonary arterial pressure both declined (P less than 0.01). However, EVLW remained unchanged, though PBV decreased significantly (peak decrease at 75 min after furosemide administration of 2.0 +/- 0.4 cc/kg, P less than 0.01). In the untreated dogs, EVLW continued to climb (P less than 0.05 vs treated dogs at 75 min postfurosemide).(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental studies on reimplantation response after lung transplantation

The reimplantation response after lung transplantation may critically impair the function of transplanted lungs in the early postoperative period. The purpose of this study is to evaluate the factors which cause this reimplantation response. Using canine left lungs, four groups were studied. Group I underwent complete hilar stripping (n = 6). Group II underwent complete hilar stripping and kept in warm ischemia for 60 min. by clamping left pulmonary artery and veins (n = 6). Group III underwent the same surgery as Group II and administered superoxide dismutase (SOD) (12000 U/kg/h) during reperfusion (n = 7). Group IV underwent autotransplantation of left lung (n = 6). To evaluate the function of left lung, arterial blood gas, pulmonary arterial pressure, aortic pressure, cardiac output and left extravascular lung water (liter EVLW) were measured in a transient contralateral pulmonary arterial occlusion before operation and 60 min. after reventilation and reperfusion. The measurement of EVLW was performed by thermal-green dye double indicator dilution method. The results obtained were as follows. 1) The values of liter EVLW measured in rt. pulmonary arterial occlusion were extremely well correlated with those of both lung EVLW. (r = 0.943 p less than 0.001). 2) The ratios of postoperative-liter EVLW: preoperative-liter EVLW and postoperative-total pulmonary resistance (TPR): preoperative-TPR were as follows: Group I; 1.29 +/- 0.19 and 1.23 +/- 0.36, Group II; 1.85 +/- 0.49 and 1.69 +/- 0.36, Group III; 1.28 +/- 0.17 and 1.50 +/- 0.36 Group IV; 2.28 +/- 0.40 and 1.70 +/- 0.34. These data indicate that the most important factor of reimplantation response at the time of this acute phase is the oxygen free radical-induced reperfusion injury. Hilar stripping, ischemic injury and surgical trauma are also important factors of reimplantation response. Vascular anastomosis is not so important when it is done well technically. 3) Administration of SOD provides protection against lung edema after lung transplantation.     

Effects of ibuprofen on a pig Pseudomonas ARDS model

The effects of ibuprofen (I) were studied in the Pseudomonas (P) porcine ARDS model. Pigs, 14-26 kg (5 in each group), were anesthetized and ventilated with 0.5 FiO2 and 5 cm H2O PEEP. A control (C) group received saline only, a second group was given P, 1 X 10(8) org/ml at 0.3 cc/20 kg/min, and a third group was given P followed by 12.5 mg I at 20 and 120 min. Pulmonary arterial (PAP), wedge (PWP) and systemic arterial pressures, cardiac output (CO), and thermal-cardiogreen extravascular lung water (EVLW), thromboxane (TxB2), 6-keto-PGF1 alpha, PaO2, PaCO2 were determined every 30 min. Albumin flux was measured with scintigraphic determination of lung:heart radioactivity ratios versus time, called slope index (SI). At 3 hr, P produced marked (P less than 0.05) increases in PAP (18 +/- 7 to 37 +/- 2 mm Hg), TxB2 (471 +/- 513 to 9216 +/- 3615 pg/ml), 6-keto-PGF1 alpha, EVLW (6.4 +/- 1.4 to 14.6 +/- 5.7 mg/kg), and SI (0.4 +/- 0.2 to 1.7 +/- 0.5 X 10(-3) U/min) with decreases in PaO2 (214 +/- 47 to 101 +/- 41 torr), CO and SAP. Ibuprofen caused a rapid clearing of TxB2 and 6-keto-PGF1 alpha associated with a transient decrease in PAP; PaO2 was considerably improved compared to P; however, CO, SAP, EVLW, and SI were unaffected. Prostaglandin blockage temporarily ameliorated the pulmonary hypertension and markedly improved oxygenation in this porcine septic ARDS model, but failed to alter increased permeability, confirming other studies that the increased pulmonary shunt in ARDS is not only dependent upon capillary leak.     

Experimental inhalation injury with concomitant surface burn: dextran resuscitation improves lung water and oxygenation.

The role of extravascular lung water (EVLW) in the pathogenesis of inhalation injury (INH) when associated with concomitant major burn (B) remains controversial. Previous experimental models have investigated isolated INH without surface burn. This study measured the effects of isolated and combined INH on EVLW and pO2 in a porcine experimental model. The beneficial effects of early resuscitation with dextran-40 (DEX) were assessed, using a control group receiving standard Parkland formula (LR). In the first part of the study (INH vs. INH + B), a group of animals with a standardized INH was compared to a group also receiving a standardized 40% BSA third-degree surface burn (n = 8, each group). With serial measurements for 5 hours, EVLW was only modestly increased unless INH was accompanied by surface burn: 20.3 +/- 4.2 vs. 32.0 +/- 4.1 ml/kg at 5 hours (p less than 0.01). Similarly, pO2 fell much more dramatically in the INH + B group, 61 +/- 5 vs. 37 +/- 5 torr (p less than 0.05). The second part of the study compared standard Parkland crystalloid resuscitation with dextran-40 resuscitation in animals receiving a combined INH + B injury (LR vs. DEX, n = 8, each group). DEX resuscitation resulted in substantially lower accumulation of EVLW out to 5 hours, 34.1 +/- 5.0 vs. 13.1 +/- 3.0 ml/kg (p less than 0.01), and significantly better pO2, 35 +/- 5 vs. 64 +/- 4 torr (p less than 0.01). Conclusions: Inhalation injury did not dramatically increase EVLW in this animal model unless accompanied by concomitant major surface burn. The deterioration in EVLW and pO2 seen in the combined injury was significantly improved with DEX resuscitation when compared to standard crystalloid resuscitation. Further study is indicated and clinical trials may be warranted.