Endotoxemia produces an increase in arterial but not venous lipid peroxides in sheep

1988 ◽  
Vol 64 (2) ◽  
pp. 592-598 ◽  
Author(s):  
R. H. Demling ◽  
C. Lalonde ◽  
P. Ryan ◽  
D. G. Zhu ◽  
Y. P. Liu
Keyword(s):  
Lung Injury ◽  
Lipid Peroxide ◽  
Lipid Peroxides ◽  
Conjugated Dienes ◽  
Base Line ◽  
Two Phase ◽  
Lymph Lipid ◽  
Protein Rich ◽  
Lung Lymph ◽  
State Increase

Our purpose was to determine the effect of an endotoxin-induced lung injury on circulating lipid peroxides. We measured both malondialdehyde (MDA) and conjugated dienes (as optical density at 233 nm) in aortic and venous plasma and lung lymph in 10 unanesthetized sheep given 1 microgram/kg of Escherichia coli endotoxin. Total lipids and prostanoids 6-ketoprostaglandin F1 alpha and thromboxane B2 were also measured. Six control sheep were also studied. Animals were monitored for a 12-h period and then killed, and lung tissue MDA was determined. A two-phase endotoxin response was noted with an initial pulmonary hypertension followed by a steady-state increase in protein-rich lung lymph flow (QL) between a 3- and 6-h period. Aortic plasma MDA was significantly increased from a base line of 4.8 +/- 1.4 to 8.9 +/- 1.6 and 7.5 +/- 1.3 nmol/ml at 1 and 4 h post-endotoxin. Aortic plasma conjugated dienes increased in all 10 sheep post-endotoxin. Venous levels of both MDA and conjugated dienes were not significantly increased. Lung QL increased two- to three-fold. Lung lymph MDA increased significantly at 1 h post-endotoxin. Lymph conjugated dienes decreased. Plasma and lymph lipid peroxide levels returned to base line by 12 h in most animals. However, tissue MDA remained significantly increased in all sheep from base line of 45 +/- 9 to 85 +/- 14 nmol/g tissue. We conclude that both MDA and conjugated dienes are transiently released into aortic plasma during endotoxin-induced oxidant lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary injury and prostaglandin production during endotoxemia in conscious sheep

1981 ◽  
Vol 240 (3) ◽  
pp. H348-H353 ◽  
Author(s):  
R. H. Demling ◽  
M. Smith ◽  
R. Gunther ◽  
J. T. Flynn ◽  
M. H. Gee
Keyword(s):  
Flow Rate ◽  
Phase 1 ◽  
Base Line ◽  
Pulmonary Injury ◽  
Two Phase ◽  
Prostanoid Production ◽  
Conscious Sheep ◽  
Pulmonary Microcirculation ◽  
Protein Rich ◽  
Lung Lymph

Prostaglandins F2 alpha, E2, and I2 (as 6-keto-PGF1 alpha) and TxA2 (as TxB2) were measured by radioimmunoassay in plasma and lymph from 12 conscious sheep with chronic lung lymph fistulas given Escherichia coli endotoxin (2-10 micrograms/kg) and followed for 24 h. Endotoxin produced a two-phase pulmonary injury. Phase 1 was characterized by transient severe pulmonary hypertension and increased lymph flow rate (QL). Plasma and lymph PGF2 alpha concentrations increased from base-line values of 0.13 +/- 0.08 and 0.30 +/- 0.10 ng/ml to 0.96 +/- 0.37 and 2.8 +/- 0.80 ng/ml, respectively. Values for TxB2 increased from 0.7 +/- 0.1 to 5.5 +/- 1.1 ng/ml in lymph and to 3.2 +/- 0.6 in plasma. Plasma PGI2 increased from 0.48 +/- 0.29 to 4.97 +/- 1.21 ng/ml and lymph PGI2 from 1.80 +/- 0.73 to 14.19 +/- 2.79 ng/ml. Phase 2 was characterized by moderately elevated pulmonary vascular pressures and a maintained high flow rate of protein-rich lymph. Lung lymph and plasma PGF2 alpha concentrations returned to base line. Lymph PGI2 decreased significantly to 5.23 +/- 2.47 ng/ml, whereas plasma PGI2 decreased to 2.70 +/- 1.07 ng/ml. We conclude that prostaglandins, particularly PGF2 alpha and prostacyclin, are released from the lung after endotoxemia and appear in lung lymph as sensitive indicators of pulmonary microvascular injury. Prostanoid production appears to temporally correspond with changes in the pulmonary microcirculation.

Lung dysfunction after thermal injury in relation to prostanoid and oxygen radical release

1986 ◽  
Vol 61 (1) ◽  
pp. 103-112 ◽  
Author(s):  
L. J. Jin ◽  
C. Lalonde ◽  
R. H. Demling
Keyword(s):  
Lipid Peroxidation ◽  
Lung Tissue ◽  
Lipid Peroxide ◽  
Lung Compliance ◽  
Base Line ◽  
Lung Water ◽  
Control Value ◽  
Lung Dysfunction ◽  
Dynamic Lung Compliance ◽  
Lung Lymph

We studied whether changes in lung function after burns (1- to 12-h period) were due to changes in lung water or airways resistance and the relationship of the changes to prostanoid and O2 radical activity (measured as lipid peroxidation). Twenty-five anesthetized mechanically ventilated adult sheep were given a 40% of body surface scald burn and resuscitated to restore and maintain base-line filling pressures. Dynamic lung compliance (Cdyn) decreased by 40% from 38 +/- 5 to 24 +/- 4 ml/cmH2O at 12 h. Venous thromboxane B2 transiently increased from 210 +/- 40 to 1,100 +/- 210 pg/ml, and the value in lung lymph increased from 180 +/- 80 to 520 +/- 80 pg/ml. Prostacyclin levels in lung lymph and plasma remained at base line. Protein-poor lung lymph flow increased two- to threefold, but postmortem lung analysis revealed no increase in lung water from the control of 3.5 +/- 0.3 g H2O/g dry wt. No increase in protein permeability was seen. However, the lipid peroxidation of lung tissue measured as malondialdehyde was significantly increased from the control value of 56 +/- 4 nmol/g lung to a value of 69 +/- 6. Ibuprofen pretreatment (12.5 mg/kg) markedly attenuated the decrease in Cdyn, with the value at 12 h being 90% of base line. Ibuprofen also decreased the amount of lung lipid peroxidation but did not decrease the lung lymph response. We conclude that the decrease in Cdyn seen early postburn is not due to increased lung water, but, rather, is due to a mediator-induced bronchoconstriction, attenuated by ibuprofen; the mediator being either thromboxane or a byproduct of O2 radicals as evidenced by increased lipid peroxide production in lung tissue.

Effects of thromboxane synthase inhibition on air emboli lung injury in sheep

1986 ◽  
Vol 60 (6) ◽  
pp. 1828-1833 ◽  
Author(s):  
M. Fukushima ◽  
T. Kobayashi
Keyword(s):  
Pulmonary Hypertension ◽  
Lung Injury ◽  
Pulmonary Artery ◽  
Air Embolism ◽  
Base Line ◽  
Pulmonary Vascular Permeability ◽  
Thromboxane Synthase ◽  
Pulmonary Hemodynamic ◽  
Synthase Inhibitor ◽  
Lung Lymph

We tested the effects of OKY-046, a thromboxane synthase inhibitor, on lung injury induced by 2 h of pulmonary air infusion (1.23 ml/min) in the pulmonary artery of unanesthetized sheep with chronic lung lymph fistula so as to assess the role of thromboxane A2 (TxA2) in the lung injury. We measured pulmonary hemodynamic parameters and the lung fluid balance. The concentrations of thromboxane B2 (TxB2) and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) in plasma and lung lymph were determined by radioimmunoassay. Air infusion caused sustained pulmonary hypertension and an increase in pulmonary vascular permeability. The levels of TxB2 and 6-keto-PGF1 alpha in both plasma and lung lymph were significantly elevated during the air infusion. TxB2 concentration in plasma obtained from the left atrium was higher than that from the pulmonary artery at 15 min of air infusion. When sheep were pretreated with OKY-046 (10 mg/kg iv) prior to the air infusion, increases in TxB2 were prevented. The pulmonary arterial pressure, however, increased similarly to that of untreated sheep (1.8 X base line). The increase in lung lymph flow was significantly suppressed during the air infusion. Our data suggest that the pulmonary hypertension observed during air embolism is not caused by TxA2.

Catalase prevents prostanoid release and lung lipid peroxidation after endotoxemia in sheep

1988 ◽  
Vol 65 (3) ◽  
pp. 1210-1216 ◽  
Author(s):  
A. Seekamp ◽  
C. Lalonde ◽  
D. G. Zhu ◽  
R. Demling
Keyword(s):  
Lipid Peroxidation ◽  
Water Content ◽  
Fold Increase ◽  
Conjugated Dienes ◽  
Base Line ◽  
Lipid Peroxidation Process ◽  
Adult Sheep ◽  
Lung Lipid ◽  
Arterial Plasma ◽  
Lung Lymph

We determined the effect of H2O2 on both the physiological and biochemical lung changes seen in the adult sheep after endotoxin. Fourteen unanesthetized adult sheep with chronic lung lymph fistula were given Escherichia coli endotoxin (1 microgram/kg) over 30 min. Seven sheep were given catalase (32,500 U/kg body wt) as an intravenous bolus 30 min before endotoxin. Four sheep were given catalase alone. Oxidant lung changes were measured using arterial plasma conjugated dienes and lung tissue malondialdehyde (MDA) content, both reflecting the lipid peroxidation process. Animals were killed 5 h after endotoxin. We found that endotoxin alone caused an early increase in pulmonary arterial pressure lung lymph flow (QL), plasma thromboxane B2, 6-keto-prostaglandin F1 alpha, and plasma conjugated dienes. A decrease in cardiac output and arterial PO2 was also seen. A three- to four-fold increase in protein-rich QL was noted at 3-4 h as well as a continued increase in arterial conjugated dienes. Lung MDA and water content were also significantly increased from base line. Catalase pretreatment significantly attenuated both the physiological changes and the prostanoid and conjugated diene release. Lung MDA and water content also remained at base line. We conclude that H2O2 plays a major role in endotoxin-induced lung injury as well as the resulting lipid peroxidation process.

Superoxide dismutase with heparin prevents increased lung vascular permeability during air emboli in sheep

1983 ◽  
Vol 55 (4) ◽  
pp. 1284-1291 ◽  
Author(s):  
M. R. Flick ◽  
J. M. Hoeffel ◽  
N. C. Staub
Keyword(s):  
Superoxide Dismutase ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Lymph Flow ◽  
Microvascular Permeability ◽  
Base Line ◽  
Pulmonary Arterial ◽  
The Right ◽  
Protein Rich ◽  
Lung Lymph

We studied the effects of bovine superoxide dismutase on the increased lung microvascular permeability to fluid and protein during air emboli in unanesthetized sheep. We measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and lymph and plasma protein concentrations. In air emboli experiments we continuously infused the same dose of air bubbles 1 mm in diameter into the right atrium of each sheep to increase pulmonary vascular resistance to 2-4 times base-line values. We did experiments in pairs so that each sheep served as its own control. We found an increase in protein-rich lymph flow from the lung during embolization in untreated sheep, indicating an increase in microvascular permeability to both fluid and protein. When we pretreated the sheep with heparin (300 U/kg) and infused them with intravenous bovine superoxide dismutase (1 mg X kg-1 X h-1 beginning before the air infusion), we found that vascular pressures and pulmonary vascular resistance were not different from untreated sheep but that the expected increases in transvascular fluid and protein flow during emboli were significantly decreased (P less than 0.0005). Heparin alone did not significantly attenuate the increased microvascular permeability but we found that it greatly enhanced the effectiveness of superoxide dismutase in preserving microvascular functional integrity during air emboli. We conclude that superoxide anion, probably produced and released by leukocytes, is a central factor in the microvascular injury that results in increased permeability in the lungs of sheep during air microembolization.

Effects of dibutyryl cAMP on pulmonary air embolism-induced lung injury in awake sheep

1987 ◽  
Vol 63 (6) ◽  
pp. 2201-2207 ◽  
Author(s):  
H. Kobayashi ◽  
T. Kobayashi ◽  
M. Fukushima
Keyword(s):  
Lung Injury ◽  
Untreated Control ◽  
Air Embolism ◽  
Intracellular Camp ◽  
Base Line ◽  
Dibutyryl Camp ◽  
Plasma Protein Concentration ◽  
Pulmonary Vascular Permeability ◽  
Pulmonary Arterial ◽  
Lung Lymph

To assess the role of intracellular adenosine 3′,5′-cyclic monophosphate (cAMP), we tested the effects of dibutyryl cAMP (DBcAMP), an analogue of cAMP, on lung injury induced by pulmonary air embolism in awake sheep with chronic lung lymph fistula. We infused air (1.23 ml/min) in the pulmonary artery for 2 h in untreated control sheep. In DBcAMP-pretreated sheep DBcAMP was infused (1 mg/kg bolus and 0.02 mg.kg-1.min-1 constantly for 5 h); after 1 h from beginning of DBcAMP administration the air infusion was started. After the air infusion, pulmonary arterial pressure (Ppa) and lung lymph flow rate (Qlym) significantly increased in both groups. DBcAMP-pretreated sheep showed significantly lower responses in Qlym (2.7 X base line) compared with untreated control sheep (4.6 X base line); however, Ppa, left atrial pressure, and lung lymph-to-plasma protein concentration ratio were not significantly different between the two groups. Although plasma and lung lymph thromboxane B2 and 6-ketoprostaglandin F1 alpha concentrations increased significantly during the air infusion, DBcAMP-pretreated sheep showed significantly lower responses. Thus DBcAMP infusion attenuated pulmonary microvascular permeability induced by air embolism. We conclude that pulmonary vascular permeability is in part controlled by the intracellular cAMP level.

Acute effects of thoracic irradiation on lung function and structure in awake sheep

1987 ◽  
Vol 62 (1) ◽  
pp. 208-218 ◽  
Author(s):  
J. E. Loyd ◽  
J. M. Bolds ◽  
J. R. Sheller ◽  
S. S. Duke ◽  
A. W. Gillette ◽  
...  
Keyword(s):  
Lung Injury ◽  
Structural Changes ◽  
Morphological Changes ◽  
Large Animal Model ◽  
Large Animal ◽  
Base Line ◽  
Structural Studies ◽  
Peripheral Lung ◽  
Lung Irradiation ◽  
Lung Lymph

To investigate the acute physiological and structural changes after lung irradiation, the effects of whole-lung irradiation were investigated in fourteen sheep. Ten sheep were prepared with vascular and chronic lung lymph catheters, then a week later were given 1,500 rad whole-lung radiation and monitored for 2 days. Four sheep were given the same dose of radiation and were killed 4 h later for structural studies. Lung lymph flow increased at 3 h after radiation (14.6 +/- 2.1 ml/h) to twice the base-line flow rate (7.5 +/- 1.3), with a high lymph-to-plasma protein concentration. Pulmonary arterial pressure increased twofold from base line (18 +/- 1.6 cmH2O) at 2 h after radiation (33 +/- 3.8). Cardiac output and systemic pressure in the aorta did not change after lung radiation. Arterial O2 tension decreased from 85 +/- 3 to 59 +/- 4 Torr at 1 day after radiation. Lymphocyte counts in both blood and lung lymph decreased to a nadir by 4 h and remained low. Thromboxane B2 concentration in lung lymph increased from base line (0.07 +/- 0.03 ng/ml) to peak at 3 h after radiation (8.2 +/- 3.7 ng/ml). The structural studies showed numerous damaged lymphocytes in the peripheral lung and bronchial associated lymphoid tissue. Quantitative analysis of the number of granulocytes in peripheral lung showed no significant change (base line 6.2 +/- 0.8 granulocytes/100 alveoli, 4 h = 10.3 +/- 2.3). The most striking change involved lung airways. The epithelial lining of the majority of airways from intrapulmonary bronchus to respiratory bronchiolus revealed damage with the appearance of intracellular and intercellular cell fragments and granules. This new large animal model of acute radiation lung injury can be used to monitor physiological, biochemical, and morphological changes after lung radiation. It is relevant to the investigation of diffuse oxidant lung injury as well as to radiobiology per se.

Concentration of aerosolized 99mTc-albumin in the pulmonary lymph of anesthetized sheep

1990 ◽  
Vol 68 (3) ◽  
pp. 1233-1240
Author(s):  
B. T. Peterson ◽  
K. D. Dickerson
Keyword(s):  
Lung Injury ◽  
Fold Increase ◽  
Lymph Flow ◽  
Base Line ◽  
A Value ◽  
Lung Epithelial ◽  
Air Space ◽  
Lung Lymph ◽  
Pulmonary Vascular Hypertension ◽  
Lung Lymph Flow

We examined the lymphatic concentration of 99mTc-albumin deposited in the air spaces of anesthetized sheep to determine whether changes in the concentration reflected changes in lung epithelial function. Five control sheep were ventilated with an aerosol of 99mTc-albumin for 6 min, and the lung lymphatic concentration of the tracer was monitored for the next 2 h. During the last 45 min the lymphatic concentration stabilized at a value that was 0.03 +/- 0.01% of the estimated value in the air spaces. Pulmonary vascular hypertension, induced in seven sheep by increasing the left atrial pressure 20 cmH2O for 4 h, increased the lung lymph flow from a base-line value of 3 +/- 2 to 21 +/- 14 ml/h. This caused the concentration of the 99mTc-albumin in the lymph to double to 0.07 +/- 0.03% of the air space concentration (P less than 0.01). Lung injury induced by infusing 0.08-0.10 ml/kg oleic acid intravenously in seven other sheep increased the lymphatic concentration of the 99mTc-albumin 10-fold to 0.31 +/- 0.09% of the air space concentration (P less than 0.01). The increased tracer concentration in the sheep with pulmonary vascular hypertension could be the result of the increased lymph flow causing a diversion of tracer into the lymphatics. However, a mathematical model showed that the 10-fold increase in the lymphatic concentration in the sheep with lung injury was primarily the result of an increase in both permeability and surface area of the epithelium that participated in the transfer of the 99mTc-albumin from the air spaces into the lung tissue drained by the lymphatics.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Vitamin E Administration on Platelet Function and Serum Lipid Peroxides in DOCA-Salt Hypertensive Rats

1991 ◽  
Vol 65 (04) ◽  
pp. 411-414 ◽  
Author(s):  
Keizo Umegaki ◽  
Hiromi Saegusa ◽  
Masato Kurokawa ◽  
Tomio Ichikawa
Keyword(s):  
Vitamin E ◽  
Platelet Function ◽  
Serum Lipid ◽  
Lipid Peroxide ◽  
Lipid Peroxides ◽  
Hypertensive Rats ◽  
Serotonin Content ◽  
Serum Lipid Peroxide ◽  
Salt Hypertension

SummaryEffects of vitamin E on platelet function and serum lipid peroxide levels were investigated in DOCA-salt hypertensive rats. In the hypertensive rats, ADP- and collagen-induced platelet aggregation in whole blood were markedly attenuated and accompanied by a reduction of serotonin content as compared with the normotensive controls. These facts indicated the appearance of exhausted platelets, which have already been activated in vivo, due to the hypertension. Platelet vitamin E levels were decreased by 50%, while serum lipid peroxide levels were increased 3.6-fold in the hypertensive rats. Vitamin E administration (10 times the dietary intake) during the experimental periods did not influence either the aggregability or the serotonin content of platelets from the hypertensive rats. However, vitamin E administration significantly prevented the elevation of serum tipid peroxides due to the hypertension. These results suggest that vitamin E administration has little effect on platelet activation in vivo due to DOCA-salt hypertension.

scholarly journals Lens Lipid Peroxides and Glutathione Concentrations in Diabetic Cataract

1997 ◽  
Vol 34 (2) ◽  
pp. 190-192 ◽  
Author(s):  
D Özmen ◽  
I Mutaf ◽  
B Özmen ◽  
J Mentes ◽  
O Bayindir
Keyword(s):  
G Protein ◽  
Lipid Peroxide ◽  
Lipid Peroxides ◽  
Thiobarbituric Acid ◽  
Thiobarbituric Acid Reactive Substances ◽  
Diabetic Cataract ◽  
Free Radical Damage ◽  
Significant Difference ◽  
Radical Damage

This study aims to explore the role of reactive oxygen radicals in the genesis of diabetic cataract. Lipid peroxide (LPO) concentrations in senile ( n = 30) and diabetic ( n = 14) cataractous lenses, were determined as thiobarbituric acid-reactive substances (TBARS) by a method modified from Satoh and Yagi, and reduced glutathione (GSH) concentrations were measured according to Beutler. Lens LPO levels (mean, SD; nmol TBARS/g protein) were significantly higher in diabetics (107·54, 18·12) than senile cataractous subjects (53·54, 15·48) ( P < 0·0001). Lens GSH levels (mean, SD; nmol/g protein) showed no significant difference between diabetics (4·29, 2·05) and senile cataractous subjects (4·68, 3·12). These results suggest that free radical damage is more effective in the genesis of diabetic cataract than in senile cataract.

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