Cerebrospinal Fluid Malondialdehyde Research Articles

The increment of annexin V-positive microvesicles versus annexin V-negative microvesicles in CSF of an animal model of Alzheimer’s disease

ObjectiveExtracellular microvesicles (MVs) as a specific signaling molecule have received much attention in nervous system studies. Alterations in the tissue redox status in pathological conditions, such as Alzheimer’s disease (AD), facilitate the translocation of cell membrane phosphatidylserine to the outer leaflet and lead to the MVs shedding. Annexin V binds with high affinity to phosphatidylserine. Some arguments exist about whether Annexin V-negative MVs should be considered in pathological conditions. Material and methodWe compared the kinetics of two phenotypes of Annexin V-positive and Annexin V-negative MVs in the cerebrospinal fluid (CSF) of amyloid-β (Aβ)-treated male Wistar rats with flow cytometry technique. The Aβ was injected bilaterally into the cerebral ventricles. Thioflavin T staining was used to confirm the presence of hippocampal Aβ fibrils two weeks post-Aβ injection. Levels of hippocampal interleukin-1β were assessed as an inflammatory index. The CSF malondialdehyde (MDA) concentration was determined. The cognitive impairment and anxiety behaviors were assessed by object recognition and elevated plus maze tests, respectively. ResultsElevation of MDA levels and a significant rise in the scoring of IL-1β staining were found in the Aβ group. The Aβ induced anxiogenic behavior, impaired novel object recognition memory, and increased the CSF levels of the total number of MVs. The number of Annexin V-positive MVs was significantly higher than Annexin V-negative MVs in all groups. ConclusionData showed that Annexin V-positive MVs potentially have a significant contribution to the pathophysiology of the Aβ-induced cognitive impairment. To catch a clear image of microvesicle production in pathological conditions, both phenotypes of Annexin V-positive and Annexin V-negative MVs should be analyzed and reported.

Continuous lumbar drainage after aneurysmal subarachnoid hemorrhage decreased malondialdehyde in cerebrospinal fluid and improved outcome

The use of a continuous lumbar drain (LD) for the treatment of aneurysmal subarachnoid hemorrhage (aSAH), and malondialdehyde (MDA), a marker of oxidative stress, is correlated with clinical outcome. This study aimed to investigate the relationship between LD placement and MDA level after aSAH. Patients with modified Fisher's grade III and IV aSAH who underwent early aneurysm obliteration were enrolled. Cerebrospinal fluid (CSF) was obtained on day 7 after aSAH in non-LD group. In LD group, the LD was inserted on day 3 after aSAH for continuous CSF drainage. The levels of intrathecal hemoglobin, total bilirubin, ferritin, and MDA were measured. There were 41 patients in non-LD group (age: 58.7±13.7 years; female: 61.0%) and 48 patients in LD group (age: 58.3±10.4 years; female: 79.2%). There were more favorable outcomes (Glasgow Outcome Scale ≥4) at 3 months after aSAH in LD group (p=0.0042). The intrathecal hemoglobin, total bilirubin, ferritin, and MDA levels at day 7 after aSAH were all significantly lower in LD group. An older age (>60 years) (p=0.0293), higher MDA level in the CSF (p=0.0208), and delayed ischemic neurological deficit (p=0.0451) were independent factors associated with unfavorable outcomes. LD placement was associated with a decreased intrathecal MDA level on day 7 after aSAH (p<0.001). The intrathecal MDA level at day 7 after aSAH can be an effective outcome indicator in modified Fisher's grade III/IV aSAH. Continuous CSF drainage via a LD can decrease the intrathecal MDA level and improve the functional outcome.

The Influence of Oxidative Stress on Neurological Outcomes in Spontaneous Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) causes, besides the primary brain injury, a secondary brain injury (SBI), which is induced, amongst other things, by oxidative stress (OS) and inflammation, determining the patient’s outcome. This study aims to assess the impact of OS in plasma and cerebrospinal fluid (CSF) on clinical outcomes in patients with ICH. A total of 19 ICH (volume > 30 cc) patients and 29 control patients were included. From day one until seven, blood and CSF samples were obtained, and ICH volume was calculated. OS markers, like malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione-sulfhydryl (GSH), and the total antioxidant status (TAS) were measured. Clinical data on treatment and outcome were determined. Patients with mRS ≤ 4 showed significantly elevated SOD and GSH-Px levels in plasma compared to patients with poor CO (p = 0.004; p = 0.002). Initial increased TAS in plasma and increased MDA in CSF were linked to an unfavorable outcome after six months (p = 0.06, r = 0.45; p = 0.05, r = 0.44). A higher ICH volume was associated with a worse outcome at week six (p = 0.04, r = 0.47). OS plays a significant role in SBI. Larger ICHs, elevated MDA in CSF, and TAS in plasma were associated with a detrimental outcome, whereas higher plasma-SOD and -GSH-Px were associated with a favorable outcome.

Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage.

Poor-grade subarachnoid hemorrhage still has a poor prognosis. This randomized controlled clinical trial evaluated intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy in patients with poor-grade subarachnoid hemorrhage. Thirty-seven patients with poor-grade subarachnoid hemorrhage were randomized to Mg+H2, Mg, and control groups. Mg and Mg+H2 groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H2 group also received intravenous hydrogen-rich solution infusion for 14 days. Primary outcome measures were occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures were modified Rankin Scale and Karnofsky performance status at 3 and 12 months, Barthel index at 12 months, and serum and cerebrospinal fluid malondialdehyde and neuron-specific enolase. Serum neuron-specific enolase levels were significantly lower in the Mg+H2 group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H2 group from days 3 to 7 than in the control group. Incidences of cerebral vasospasm and delayed cerebral ischemia were significantly higher in the control group than in other groups. Modified Rankin Scale and Karnofsky performance status did not significantly differ between the three groups at 3 months. Modified Rankin Scale scores 0 to 2 were more common in the Mg and Mg+H2 groups at 1 year. Barthel index was higher in the Mg+H2 group than in the control group. Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects. Registration: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000014696.

Lipid Peroxidation and Antioxidant Consumption as Early Markers of Neurosurgery-Related Brain Injury in Children.

Lipid peroxidation represents a marker of secondary brain injury both in traumatic and in non-traumatic conditions-as in major neurosurgical procedures-eventually leading to brain edema amplification and further brain damage. Malondialdehyde (MDA), a lipid peroxidation marker, and ascorbate, a marker of antioxidant status, can represent early indicators of this process within the cerebrospinal fluid (CSF). We hypothesized that changes in cerebral lipid peroxidation can be measured ex vivo following neurosurgery in children. Thirty-six children (M:F = 19/17, median age 32.9months; IQR 17.6-74.6) undergoing neurosurgery for brain tumor removal were admitted to the pediatric intensive care unit (PICU) in the postoperative period with an indwelling intraventricular catheter for intracranial pressure monitoring and CSF drainage. Plasma and CSF samples were obtained for serial measurement of MDA, ascorbate, and cytokines. An early brain-limited increase in lipid peroxidation was measured, with a significant increase from baseline of MDA in CSF (p = 0.007) but not in plasma. In parallel, ascorbate in CSF decreased (p = 0.05). Systemic inflammatory response following brain surgery was evidenced by plasma IL-6/IL-8 increase (p 0.0022 and 0.0106, respectively). No correlation was found between oxidative response and tumor site or histology (according to World Health Organization grading). Similarly, lipid peroxidation was unrelated to the length of surgery (mean 321 ± 73min), or intraoperative blood loss (mean 20.9 ± 16.8% of preoperative volemia, 44% given hemotransfusions). Median PICU stay was 3.5days (IQL range 2-5.5 d.), and postoperative ventilation need was 24h (IQL range 20-61.5h). The elevation in postoperative MDA in CSF compared with preoperative values correlated significantly with postoperative ventilation need (P = 0.05, r2 0168), while no difference in PICU stay was recorded. Our results indicate that lipid peroxidation increases consistently following brain surgery, and it is accompanied by a decrease in antioxidant defences; intraventricular catheterization offers a unique chance of oxidative process monitoring. Further studies are needed to evaluate whether monitoring post-neurosurgical oxidative stress in CSF is of prognostic utility.

Novel biomarker for neurodegenerative diseases- motor neuron disease (MND), cerebellar ataxia (CA) and Parkinson's disease (PD)

Oxygen is the most mandatory component of living organism and it may at times produce highly reactive species, the free radicals, which are destructive to normal living tissues. Degenerative diseases of central nervous system (CNS) are quite common, contributing significantly to morbidity as well as mortality %. In neurodegenerative diseases such as motor neuron disease (MND), Cerebellar Ataxia (CA) and Parkinson's disease (PD), there is no direct evidence for involvement of metals and free radicals in the etiology but circumstantial evidence provides a hypothesis that alteration in metals and free radicals contribute to the pathogenesis of neurodegeneration in these disorders. The aim of the present study was to estimate free radicals cascade i.e. damage caused in terms of malondialdehyde (MDA) and defense system Superoxide dismutase (SOD) and catalase in blood and cerebro-spinal fluid (CSF) of neurodegenerative diseases (MND, CA and PD), to analyze correlation with level of free radical and the clinical variables like age, severity of diseases and duration of illness and any possibility from this clinical parameters to identify a biomarker for diagnosis of neurodegenerative diseases. The level of MDA in CSF was 0.46 ± 0.17 in case of MND, 0.49 ± 0.13 in case of CA and 0.47 ± 0.16 in case of PD as compared control group (0.22 ± 0.06) whereas in blood MDA level was 0.10 ± 0.04 in case of MND, 0.33 ± 0.41 in case of CA and 0.47 ± 0.46 in case of PD as compared control group (0.04 ± 0.03). It was found to be highly significant (p < .001). In CSF and blood both catalase activity was statistically significantly higher as compared to control group of all cases (MND, CA and PD) and SOD activity was statistically significantly lower as compared to control group of all cases. Free radical parameters in human CSF might be a novel biomarker for the early clinical identification of neurodegenerative diseases.

Serum and cerebrospinal fluid excitatory amino acid, nitric oxide and cerebrospinal fluid malondialdehyde levels in West syndrome

West syndrome (WS) is an epileptic syndrome of early childhood. There have been a limited numbers of studies of cerebrospinal fluid (CSF) excitatory amino acid (EAA), nitric oxide (NO), and malondialdehyde (MDA) levels, as well as plasma levels of EAA, and NO, in WS. In this article, CSF EAA, NO, and MDA levels and plasma EAA, NO status, and a determination of the effects of antiepileptic drug therapy on these values were investigated in children with WS. Evaluation of CSF and serum EAA, NO, and MDA levels and of serum EAA and NO levels after 3 mo of antiepileptic drug therapy revealed a statistically significant decrease in CSF aspartate, glutamate, NO and MDA levels. In conclusion, the decrease in CSF MDA levels in this study is the result of both the decrease in glutamate activity and neuronal damage after controlling seizures with antiepileptic drugs.

Changes in vitamin C and oxidative stress status during the treatment of tuberculous meningitis

Tuberculosis (TB) is associated with oxidative stress and is traditionally linked to vitamin C deficiency. To evaluate the time course of the oxidative stress marker, malondialdehyde (MDA), and vitamin C status during the clinical treatment of tuberculous meningitis (TBM). MDA and vitamin C reduction/oxidation (redox) status were spectrophotometrically measured at admission and during hospital treatment in cerebrospinal fluid (CSF) and serum from 27 TBM patients and 20 controls. Baseline CSF and serum MDA levels in TBM patients were higher than in controls (both P < 0.05), and remained elevated throughout the study. CSF MDA steadily increased from baseline 0.66 ± 0.24 mol/l to 1.02 ± 0.33 μmol/l at the end of the sixth week of treatment (P < 0.05), and then returned to baseline levels. Baseline CSF and serum total vitamin C were lower in TBM patients than in controls, but were soon normalised. CSF and serum ascorbate, reduced/oxidised vitamin C ratios and ascorbate CSF/serum ratio were markedly decreased in TBM patients (P < 0.05), and showed no improvement during treatment. These results indicate increased local and systemic oxidative stress, accompanied by impaired redox status, but not total vitamin C deficiency, which persisted during conventional clinical treatment of TBM.

Oxidant and Antioxidant Status in Children With Subacute Sclerosing Panencephalitis

We analyzed serum alpha-tocopherol, beta-carotene, retinol, and ascorbic acid levels and malondialdehyde and reduced glutathione concentrations on erythrocyte and cerebrospinal fluid in 30 patients with subacute sclerosing panencephalitis to evaluate oxidant and antioxidant status. Serum alpha-tocopherol, beta-carotene, retinol, ascorbic acid levels, and erythrocyte and cerebrospinal fluid reduced glutathione concentrations were decreased; however, erythrocyte and cerebrospinal fluid malondialdehyde levels were increased in the patients. Cerebrospinal fluid malondialdehyde levels were different between clinical stages of the disease (P < .05). Higher cerebrospinal fluid malondialdehyde level was associated with the more severe clinical stage. A positive correlation was found between cerebrospinal fluid malondialdehyde level and clinical stages (r = 0.42; P < .05) and between erythrocyte malondialdehyde level and clinical stages (r = 0.40; P < .05). Our findings showed presence of oxidative damage in subacute sclerosing panencephalitis and that antioxidants were increased as defense mechanisms of the organism against oxidative damage.

Oxidative Stress in Children with Bacterial Meningitis

Bacterial meningitis is a common cause of morbidity and mortality in children. The oxidative stress in bacterial meningitis is barely determined. Forty children with bacterial meningitis were studied for their oxidants and antioxidants status in serum and cerebrospinal fluid. Fever (95%) was commonest presentation followed by seizure and vomiting. Neck rigidity and Kernig's sign were present in 37.5% and 27.5% cases, respectively. Plasma and cerebrospinal fluid malondialdehyde, protein carbonyl and nitrite levels were significantly raised in cases (p < 0.001). Plasma and cerebrospinal fluid ascorbic acid, glutathione and superoxide dismutase levels were significantly decreased in children with septic meningitis (p < 0.001). Significantly elevated malondialdehyde, nitrite and protein carbonyl levels reflect increased oxidative stress, whereas decreased concentrations of glutathione, ascorbic acid and superoxide dismutase indicates utilization of the antioxidants in septic meningitis. Thus, changes in oxidants and antioxidants observed suggest production of reactive oxygen species and their possible role in pathogenesis of septic meningitis.

Serum and Cerebrospinal Fluid Antioxidant Activity and Lipid Peroxidation in Guillain–Barre Syndrome and Multiple Sclerosis Patients

ABSTRACTOxidative stress through the changes in the levels of reactive oxygen species and antioxidative parameters can cause various neurological disorders. The aim of the present study was to show antioxidant activity (AOA) and malondialdehyde (MDA) levels in affected people with Guillain–Barre syndrome (GBS) and multiple sclerosis (MS). A total of 15 GBS patients, 13 MS patients, and 15 age and sex matched controls were included in this study. MDA and AOA values were determined in both cerebrospinal fluid (CSF) and serum, spectrophotometrically. We have shown an increase in the values of MDA in the CSF of both GBS and MS patients (0.32 ± 0.073 and 0.22 ± 0.06 μmol/L) compared to the control (undetectable levels). Furthermore, a significant decrease in the serum MDA levels was shown in both GBS and MS patients (0.81 ± 0.18 and 0.73 ± 0.18 μmol/L) when compared to the control (1.7 ± 0.46 μmol/L). A decrease was shown for serum AOA in both GBS (1.7 ± 0.21 mmol/L) and MS patients (2.6 ± 0.62 mmol/L) when compared to the control (3.2 ± 0.17 mmol/L). However, a significant increase in the values of CSF AOA was shown in both MS and GBS patients (1.47 ± 0.19 and 1.42 ± 0.26 mmol/L) compared to the control (0.71 ± 0.19 mmol/L). An imbalance between the levels of AOA and MDA in both CSF and serum can be followed in both MS and GBS patients.

PLASMA AND CEREBROSPINAL FLUID HOMOCYSTEINE, NITRIC OXIDE AND MALONDIALDEHYDE LEVELS IN ACUTE ISCHEMIC STROKE: POSSIBLE ROLE OF FREE RADICALS IN THE DEVELOPMENT OF BRAIN INJURY

Aim: Free radical mechanisms may play an important role in brain ischemia / reperfusion injury. The generation of reactive oxygen species by homocysteine (Hcy) or nitric oxide (NO) metabolism might be involved in the induction of lipid peroxidation, as indicated by malondialdehyde (MDA) formation. The purpose of this study was to investigate the behavior of Hcy, NO and MDA in plasma and cerebrospinal fluid (CSF) within 4 days after ischemic stroke onset. Methods: The levels of NO, Hcy and MDA were determined in plasma and CSF on the 3rd or 4th days after the onset of ischemic stroke in 29 patients (12 men and 17 women) and in 13 healthy controls (6 men and 7 women) of comparable age and gender. Results: The plasma MDA, NO and Hcy levels were significantly higher in the stroke patients, while mean MDA, NO and Hcy levels in CSF showed a significant increase in the cases as compared to controls (p<0.01). There were no gender-specific differences in the plasma or CSF MDA, NO and Hcy concentrations. A significant negative correlation was found between duration of diabetes with CSF NO (r=-0.63, p<0.001). The low Glasgow Coma Scale (GKS) was negatively correlated with lethal outcome, (r=-0.76, p<0.001), but it did not correlate significantly with any of the measured parameters. Conclusion: These data support that free radical mechanisms may play a role in the development of brain injury following ischemic stroke. It was suggested that the elevated Hcy may be an important risk factor for acute ischemic cerebral injury.

Oxidative Stress in Perinatal Asphyxia

Oxygen free radicals may cause tissue injury in perinatal asphyxia. We measured plasma and cerebrospinal fluid levels of malondialdehyde and plasma levels of glutathione peroxidase, catalase, and superoxide dismutase in 50 term newborns with perinatal asphyxia and eight newborns without asphyxia. Neonates with sepsis, major congenital malformations, and hemolytic disease were excluded. The levels of plasma and cerebrospinal fluid malondialdehyde, as well as of plasma glutathione peroxidase, catalase, and superoxide dismutase, were significantly higher in newborns with perinatal asphyxia, and demonstrated a progressive increase with greater severity of hypoxic ischemic encephalopathy. Higher levels of plasma and cerebrospinal fluid malondialdehyde and plasma catalase were documented in newborns who died from hypoxic ischemic encephalopathy, compared with those who survived, but no such difference was found in plasma levels of glutathione peroxidase and superoxide dismutase. The data of the present study suggest that, despite the increased activities of antioxidant enzymes in perinatal asphyxia, these neonates experience higher degrees of oxidative stress, as evidenced by increased levels of plasma and cerebrospinal fluid malondialdehyde. Hence, oxygen free radicals can be considered to play a significant role in the pathophysiology of perinatal asphyxia.

Effects of Febrile and Afebrile Seizures on Oxidant State in Children

No comparative studies have addressed the oxidant and antioxidant states of blood and cerebrospinal fluid. To reveal this differential state, the study was designed to identify the seizure type with the worse prognosis by determining erythrocyte arginase and erythrocyte catalase, plasma and cerebrospinal fluid malondialdehyde, and plasma and cerebrospinal fluid nitric oxide levels. Study groups were classified as febrile (group 1, n = 21), afebrile (group 2, n = 21), and control (group 3, n = 41, subdivided as 3a, febris positive, convulsion negative, and 3b, febris negative, convulsion negative). Levels of erythrocyte arginase, erythrocyte catalase, plasma malondialdehyde, cerebrospinal fluid malondialdehyde, plasma nitric oxide, and cerebrospinal fluid nitric oxide levels were determined for all groups. A difference was detected between the control and febrile seizure groups with respect to erythrocyte catalase and plasma and cerebrospinal fluid levels of nitric oxide (P < 0.05). Both febrile states and convulsions influence oxidative mechanism. Oxidative stress-generating potential differs for febrile and afebrile seizures. In afebrile seizures, greater levels of oxidative stress might affect prognosis adversely. This phenomenon can be interpreted in terms of fever as a protective factor against possible neurological damage during convulsive seizures.

Effect of corticosteroid therapy on serum and CSF malondialdehyde and antioxidant proteins in multiple sclerosis.

Multiple sclerosis (MS) is a disease characterised by perivascular infiltrates and demyelination of the white matter in the central nervous system. Although the precise cause of MS remains unknown, some investigations have been carried out on antioxidant mechanisms in these patients. In this study, malondialdehyde (MDA), as a lipid peroxidation marker, and ceruloplasmin (Cp) and transferrin (Trf), as antioxidant proteins, levels were determined in cerebrospinal fluid (CSF) and serum of 30 MS patients before and after corticosteroid therapy and in 20 control subjects. Transferrin and Cp levels were measured by the nephelometric method and MDA was measured spectrophotometrically. Mean MDA(serum) and MDA(CSF) levels were found to be highest in the pretreatment group and lowest in the control group. Although there was no significant difference in terms of serum Trf level, serum Cp was found higher in pre- and posttreatment groups than in the control groups. Ceruloplasmin and Trf levels of CSF were not detectable using the nephelometric method. A significant correlation was found between MDA(CSF) and MDA(serum) in the pretreatment group (r=0.58). These data revealed that lipid peroxidation was increased in serum and particulary in CSF of MS patients and was reduced with corticosteroid therapy.

Malondialdehyde, Glutathione Peroxidase, and Superoxide Dismutase in Cerebrospinal Fluid During Cerebral Vasospasm in Monkeys

Cerebral vasospasm may result from lipid peroxidation induced by oxyhemoglobin in the subarachnoid space after subarachnoid hemorrhage. To test this theory, vasospasm was induced in monkeys by intrathecal injections of oxyhemoglobin or supernatant fluid from autologous blood incubated in vitro. Concentration of malondialdehyde (MDA), a product of lipid peroxidation, was elevated in cerebrospinal fluid (CSF) in association with vasospasm caused by oxyhemoglobin and supernatant fluid. Intrathecal injections of methemoglobin or bilirubin did not cause vasospasm or increased CSF MDA. Activity of glutathione peroxidase in CSF increased significantly after injection of oxyhemoglobin and methemoglobin. There were no significant changes in CSF superoxide dismutase activity although there was a trend towards higher activities in animals treated with oxyhemoglobin, methemoglobin, bilirubin, and supernatant fluid. These results show oxyhemoglobin-induced vasospasm is associated with MDA and lipid peroxidation in the subarachnoid space. Furthermore, detection of peroxidation products after injection of oxyhemoglobin in the absence of erythrocyte membranes indicates that oxyhemoglobin may directly damage cerebral arteries and brain by inducing lipid peroxidation in these structures. Depletion of free-radical scavenging enzymes in CSF did not seem necessary for development of vasospasm. In fact, there was a tendency for vasospasm to elevate enzyme activities, as if production of scavengers was induced by excess free radicals in the subarachnoid space.

Pathogenesis of pulmonary edema associated with intracisternal endotoxin in dogs

To examine the role of central nervous system injury in the pathogenesis of pulmonary edema, we injected Escherichia coli endotoxin (5 mg/kg) into the cisterna magna of six dogs (group E) and compared, over 4 h, both the pulmonary edema and cerebrospinal fluid (CSF) abnormalities with those in six control dogs (group C). In group E, intracisternal endotoxin raised intracranial pressure from 21 +/- 6 to 38 +/- 8 cmH2O (P less than 0.001), CSF total protein from 18 +/- 6 to 54 +/- 19 mg/dl (P less than 0.001), and CSF malondialdehyde from 0.12 +/- 0.11 to 0.61 +/- 0.35 nmol/ml (P less than 0.05); all were unchanged in group C. When the pulmonary wedge pressure was maintained at 10 mmHg by fluid infusion, extravascular thermal volume in group E increased from 7.2 +/- 1.2 to 12.0 +/- 2.7 ml/kg (P less than 0.005) at 4 h when the excised lungs weighed 13.6 +/- 1.5 g/kg; in group C, extravascular thermal volume did not increase, and the excised lungs weighed less (10.8 +/- 1.3 g/kg, P less than 0.05) than those in group E. The dry weights of the lungs were not different between groups, and the alveolar lining fluid-to-plasma albumin ratio in both groups remained low, 0.1-0.2. Fluid infusion in group E (9.2 +/- 2.9 liters) caused colloid oncotic pressure to decrease 4.5 +/- 2.8 mmHg; colloid oncotic pressure fell less (0.8 +/- 1.9 mmHg, P less than 0.001) in group C as less fluid (2.2 +/- 1.5 liters, P less than 0.001) was required to maintain pulmonary wedge pressure.(ABSTRACT TRUNCATED AT 250 WORDS)