scholarly journals Alveolar Overdistension as a Cause of Lung Injury: Differences among Three Animal Species

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Manuel García-Delgado ◽  
Inés Navarrete-Sánchez ◽  
Virginia Chamorro-Marín ◽  
Juan Carlos Díaz-Monrové ◽  
Javier Esquivias ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Animal Species ◽  
Tension Pneumothorax ◽  
Weight Ratio ◽  
Dry Weight ◽  
In Vivo Studies ◽  
High Tidal Volume ◽  
Alveolar Collapse ◽  
Alveolar Overdistension

This study analyses characteristics of lung injuries produced by alveolar overdistension in three animal species. Mechanical ventilation at normal tidal volume (10 mL/Kg) and high tidal volume (50 mL/Kg) was applied for 30 min in each species. Data were gathered on wet/dry weight ratio, histological score, and area of alveolar collapse. Five out of six rabbits with high tidal volume developed tension pneumothorax, and the rabbit results were therefore not included in the histological analysis. Lungs from the pigs and rats showed minimal histological lesions. Pigs ventilated with high tidal volume had significantly greater oedema, higher neutrophil infiltration, and higher percentage area of alveolar collapse than rats ventilated with high tidal volume. We conclude that rabbits are not an appropriate species for in vivo studies of alveolar overdistension due to their fragility. Although some histological lesions are observed in pigs and rats, the lesions do not appear to be relevant.

scholarly journals Ibuprofen Protects Ventilator-Induced Lung Injury by Downregulating Rho-Kinase Activity in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Liang-Ti Huang ◽  
Chien-Huang Lin ◽  
Hsiu-Chu Chou ◽  
Chung-Ming Chen
Keyword(s):  
Lung Injury ◽  
Protein Expression ◽  
Tidal Volume ◽  
Kinase Activity ◽  
Rho Kinase ◽  
Weight Ratio ◽  
Dry Weight ◽  
High Tidal Volume ◽  
Rhoa Activity ◽  
Ventilator Induced Lung Injury

Background. Ventilator-induced lung injury-(VILI-) induced endothelial permeability is regulated through the Rho-dependent signaling pathway. Ibuprofen inhibits Rho activation in animal models of spinal-cord injury and Alzheimer’s disease. The study aims to investigate ibuprofen effects on high tidal volume associated VILI.Methods. Twenty-eight adult male Sprague-Dawley rats were randomized to receive a ventilation strategy with three different interventions for 2 h: (1) a high-volume zero-positive end-expiratory pressure (PEEP) (HVZP) group; (2) an HVZP + ibuprofen 15 mg/kg group; and (3) an HVZP + ibuprofen 30 mg/kg group. A fourth group without ventilation served as the control group. Rho-kinase activity was determined by ratio of phosphorylated ezrin, radixin, and moesin (p-ERM), substrates of Rho-kinase, to total ERM. VILI was characterized by increased pulmonary protein leak, wet-to-dry weight ratio, cytokines level, and Rho guanine nucleotide exchange factor (GEF-H1), RhoA activity, p-ERM/total ERM, and p-myosin light chain (MLC) protein expression.Results. Ibuprofen pretreatment significantly reduced the HVZP ventilation-induced increase in pulmonary protein leak, wet-to-dry weight ratio, bronchoalveolar lavage fluid interleukin-6 and RANTES levels, and lung GEF-H1, RhoA activity, p-ERM/total ERM, and p-MLC protein expression.Conclusion. Ibuprofen attenuated high tidal volume induced pulmonary endothelial hyperpermeability. This protective effect was associated with a reduced Rho-kinase activity.

Immunotargeting of catalase to lung endothelium via anti-angiotensin-converting enzyme antibodies attenuates ischemia-reperfusion injury of the lung in vivo

2007 ◽  
Vol 293 (1) ◽  
pp. L162-L169 ◽  
Author(s):  
Kai Nowak ◽  
Sandra Weih ◽  
Roman Metzger ◽  
Ronald F. Albrecht ◽  
Stefan Post ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Dry Weight ◽  
Serum Levels ◽  
Converting Enzyme ◽  
Pulmonary Endothelium ◽  
Preferential Expression

Limitation of reactive oxygen species-mediated ischemia-reperfusion (I/R) injury of the lung by vascular immunotargeting of antioxidative enzymes has the potential to become a promising modality for extension of the viability of banked transplantation tissue. The preferential expression of angiotensin-converting enzyme (ACE) in pulmonary capillaries makes it an ideal target for therapy directed toward the pulmonary endothelium. Conjugates of ACE monoclonal antibody (MAb) 9B9 with catalase (9B9-CAT) have been evaluated in vivo for limitation of lung I/R injury in rats. Ischemia of the right lung was induced for 60 min followed by 120 min of reperfusion. Sham-operated animals (sham, n = 6) were compared with ischemia-reperfused untreated animals (I/R, n = 6), I/R animals treated with biotinylated catalase (CAT, n = 6), and I/R rats treated with the conjugates (9B9-CAT, n = 6). The 9B9-CAT accumulation in the pulmonary endothelium of injured lungs was elucidated immunohistochemically. Arterial oxygenation during reperfusion was significantly higher in 9B9-CAT (221 ± 36 mmHg) and sham (215 ± 16 mmHg; P < 0.001 for both) compared with I/R (110 ± 10 mmHg) and CAT (114 ± 30 mmHg). Wet-dry weight ratio of I/R (6.78 ± 0.94%) and CAT (6.54 ± 0.87%) was significantly higher than of sham (4.85 ± 0.29%; P < 0.05), which did not differ from 9B9-CAT (5.58 ± 0.80%). The significantly lower degree of lung injury in 9B9-CAT-treated animals compared with I/R rats was also shown by decreased serum levels of endothelin-1 (sham, 18 ± 9 fmol/mg; I/R, 42 ± 12 fmol/mg; CAT, 36 ± 11 fmol/mg; 9B9-CAT, 26 ± 9 fmol/mg; P < 0.01) and mRNA for inducible nitric oxide synthase (iNOS) [iNOS-GAPDH ratio: sham, 0.15 ± 0.06 arbitrary units (a.u.); I/R, 0.33 ± 0.08 a.u.; CAT, 0.26 ± 0.05 a.u.; 9B9-CAT, 0.14 ± 0.04 a.u.; P < 0.001]. These results validate immunotargeting by anti-ACE conjugates as a prospective and specific strategy to augment antioxidative defenses of the pulmonary endothelium in vivo.

Impairment of transalveolar fluid transport and lung Na+-K+-ATPase function by hypoxia in rats

1999 ◽  
Vol 87 (3) ◽  
pp. 962-968 ◽  
Author(s):  
Satoshi Suzuki ◽  
Masafumi Noda ◽  
Makoto Sugita ◽  
Sadafumi Ono ◽  
Kaoru Koike ◽  
...  
Keyword(s):  
Fluid Transport ◽  
Weight Ratio ◽  
Dry Weight ◽  
Hydrolytic Activity ◽  
Hypoxic Exposure ◽  
Blue Dye ◽  
Alveolar Type ◽  
Alveolar Fluid Clearance ◽  
Exposure In Vivo

We examined whether hypoxic exposure in vivo would influence transalveolar fluid transport in rats. We found a significant decrease in alveolar fluid clearance of the rats exposed to 10% oxygen for 48 h. Terbutaline did not stimulate alveolar fluid clearance, and alveolar fluid cAMP levels were lower than those determined in normoxia experiment. Hypoxia did not influence the alveolar fluid lactate dehydrogenase levels, Evans blue dye fluid-to-serum concentration ratio, or lung wet-to-dry weight ratio, indicating no significant change in the permeability of alveolar-capillary barrier. Histological examination showed no significant fluid accumulation into the interstitium and the alveolar space. Hypoxia did not reduce lung ATP content; however, we found significant decrease in Na+-K+-ATPase hydrolytic activity in lung tissue preparations and isolated alveolar type II cells. Our data indicate that hypoxic exposure in vivo impairs transalveolar fluid transport, and this impairment is related to the decrease in alveolar epithelial Na+-K+-ATPase hydrolytic activity but is not secondary to the alteration of cellular energy source.

Stress wave velocity measured in intact pig lungs with cross-spectral analysis

1994 ◽  
Vol 76 (2) ◽  
pp. 565-571 ◽  
Author(s):  
M. Jahed ◽  
S. J. Lai-Fook
Keyword(s):  
Spectral Analysis ◽  
Stress Wave ◽  
Intratracheal Instillation ◽  
Weight Ratio ◽  
Transpulmonary Pressure ◽  
Dry Weight ◽  
Stress Waves ◽  
Wave Velocities ◽  
Esophageal Balloon

In anesthetized pigs (25–40 kg), we generated stress waves in the lung by rapid deflation of an esophageal balloon. The source distortion was measured by an accelerometer (1 g wt) bonded to the balloon. Stress waves were detected by three accelerometers bonded to intercostal muscle and to the skin near midchest. The distance between the source and chest receivers were measured radiographically. Cross-spectral analysis was used to calculate transit times. We measured stress wave velocities at airway pressures of 0 (functional residual capacity) and 25 cmH2O. Transpulmonary pressure (Ptp) was measured by an esophageal balloon. In vivo, stress wave velocities increased from 291 +/- 117 (SD) cm/s at 3.0 +/- 0.9 cmH2O Ptp to 573 +/- 73 cm/s at 13.8 +/- 3.5 cmH2O Ptp (n = 6). These velocities agreed with longitudinal wave velocities measured in isolated sheep lungs and predictions based on the elastic moduli of lung parenchyma. Post-mortem edema was induced by intratracheal instillation of 200 ml of saline, resulting in a wet-to-dry weight ratio of 7.7 +/- 1.4 (n = 5). At 15 cmH2O Ptp, stress wave velocities decreased from 565 +/- 155 cm/s before edema to 445 +/- 130 cm/s after edema. This decrease correlated well with predictions based on the increased lung density, as dictated by elasticity theory.

Inhibition of matrix metalloproteinase-9 prevents neutrophilic inflammation in ventilator-induced lung injury

2006 ◽  
Vol 291 (4) ◽  
pp. L580-L587 ◽  
Author(s):  
Je Hyeong Kim ◽  
Min Hyun Suk ◽  
Dae Wui Yoon ◽  
Seung Heon Lee ◽  
Gyu Young Hur ◽  
...  
Keyword(s):  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Tidal Volume ◽  
Weight Ratio ◽  
Dry Weight ◽  
Neutrophil Infiltration ◽  
Neutrophilic Inflammation ◽  
Ventilator Induced Lung Injury ◽  
Metalloproteinase 9 ◽  
Expression And Activity

Neutrophils are considered to play a central role in ventilator-induced lung injury (VILI). However, the pulmonary consequences of neutrophil accumulation have not been fully elucidated. Matrix metalloproteinase-9 (MMP-9) had been postulated to participate in neutrophil transmigration. The purpose of this study was to investigate the role of MMP-9 in the neutrophilic inflammation of VILI. Male Sprague-Dawley rats were divided into three groups: 1) low tidal volume (LVT), 7 ml/kg of tidal volume (VT); 2) high tidal volume (HVT), 30 ml/kg of VT; and 3) HVT with MMP inhibitor (HVT+MMPI). As a MMPI, CMT-3 was administered daily from 3 days before mechanical ventilation. Degree of VILI was assessed by wet-to-dry weight ratio and acute lung injury (ALI) scores. Neutrophilic inflammation was determined from the neutrophil count in the lung tissue and myeloperoxidase (MPO) activity in the bronchoalveolar lavage fluid (BALF). MMP-9 expression and activity were examined by immunohistochemical staining and gelatinase zymography, respectively. The wet-to-dry weight ratio, ALI score, neutrophil infiltration, and MPO activity were increased significantly in the HVT group. However, in the HVT+MMPI group, pretreatment with MMPI decreased significantly the degree of VILI, as well as neutrophil infiltration and MPO activity. These changes correlated significantly with MMP-9 immunoreactivity and MMP-9 activity. Most outcomes were significantly worse in the HVT+MMPI group compared with the LVT group. In conclusion, VILI mediated by neutrophilic inflammation is closely related to MMP-9 expression and activity. The inhibition of MMP-9 protects against the development of VILI through the downregulation of neutrophil-mediated inflammation.

Shen-Fu Attenuates Endotoxin-Induced Acute Lung Injury in Rats

2006 ◽  
Vol 34 (04) ◽  
pp. 613-621 ◽  
Author(s):  
Yanning Qian ◽  
Jie Sun ◽  
Zhongyun Wang ◽  
Jianjun Yang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Inflammation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Nf Kappa B ◽  
Lung Weight ◽  
Tnf Α ◽  
Male Wistar Rats

Sepsis is associated with the highest risk of progression to acute lung injury or acute respiratory distress syndrome. Shen-Fu has been advocated to treat many severely ill patients. Our study was designed to investigate the effect of Shen-Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were randomly divided into 6 groups: controls; those challenged with endotoxin (5 mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100 mg/kg). TNF-α, IL-6, and NF-kappa B were investigated in the lung two hours later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated six hours later. Intravenous administration of endotoxin provoked significant lung injury, which was characterized by increment increase of MPO activity and wet/dry lung weight ratio, and TNF-α and IL-6 expression and NF-kappa B activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight ratio and inhibited TNF-α and IL-6 production, endotoxin-induced NF-kappa B activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg inhibited endotoxin-induced pulmonary inflammation in vivo.

Temperature affects lung fluid and recoil during high tidal ventilation at low resting volume

1987 ◽  
Vol 63 (5) ◽  
pp. 1705-1710
Author(s):  
T. Horie ◽  
T. Izumi ◽  
K. Hodaka ◽  
T. Akashiba ◽  
Y. Hosokawa ◽  
...  
Keyword(s):  
Activity Index ◽  
Weight Ratio ◽  
Dry Weight ◽  
Elastic Recoil ◽  
Edema Formation ◽  
Lung Fluid ◽  
Open Chest ◽  
Tidal Ventilation ◽  
Minimum Surface Tension

Effects of tidal volume (VT), end-expiratory pressure (EEP), and environmental temperature (Tenv) on elastic recoil force (Pel) and edema formation were examined in open-chest anesthetized rabbits. Sixty-two rabbits in four groups were ventilated for 3 h with VT of either 10 or 25 ml/kg body wt, EEP of 0 or 2 cmH2O, and Tenv of 18 or 35 degrees C. After ventilation, Pel at 80% of total lung capacity (P80) was significantly increased when ventilation was performed with the combination of large VT, 0 EEP, and low Tenv. This change was prevented by altering any one of the three conditions, e.g., small VT, positive EEP, or high Tenv. Similarly, elevation of minimum surface tension and reduction of surface activity index of lavages from excised lungs after ventilation were observed only when increased P80 was noted. Additionally, the increase of P80 was well correlated with increment of wet weight-to-dry weight ratio and degree of perivascular cuffing and alveolar edema formation of excised lungs. These results indicate that elevation of Pel after high tidal ventilation in open-chest animals in vivo was influenced by level of EEP and Tenv and that the degree of edema formation was closely related to the increase of Pel. The increased Pel is presumably primary and causes fluid accumulation.

186Re-HEDP: A Potential Therapeutic Bone Agent

1984 ◽  
Vol 23 (02) ◽  
pp. 81-82 ◽  
Author(s):  
A. R. Ketring ◽  
E. A. Deutsch ◽  
J. Weininger
Keyword(s):  
Chromatographic Analysis ◽  
Animal Species ◽  
In Vivo Studies ◽  
High Pressure Liquid Chromatographic ◽  
Normal Bone ◽  
Liquid Chromatographic Analysis ◽  
Main Component ◽  
Liquid Chromatographic

SummaryA lyophilized kit preparation of HEDP for labelling with 186Re has been developed as a potential bone agent useful for both diagnosis and therapy. High pressure liquid chromatographic analysis showed that the 186Re-HEDP is a mixture of several components. Preliminary in vivo studies in several animal species showed that both the 186Re-HEDP mixture and the HPLC-purified main component are bone-seeking agents with slow blood and soft-tissue clearance rates. HPLC purification slightly improved the quality of the image. In mice and rats with trauma-induced osteogenetic activity in one leg, the bone uptake of the traumatized leg was 1.7-1.9 times higher than of the normal leg. The lesion-to-normal bone ratio was 4-5.4.

scholarly journals Tidal volume dependency of gas exchange in bronchoconstricted pig lungs

2007 ◽  
Vol 103 (1) ◽  
pp. 148-155 ◽  
Author(s):  
Axel Kleinsasser ◽  
I. Mark Olfert ◽  
Alex Loeckinger ◽  
G. Kim Prisk ◽  
Susan R. Hopkins ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Dynamic Compliance ◽  
Inert Gas ◽  
High Tidal Volume ◽  
Pulmonary Resistance ◽  
Mechanically Ventilated ◽  
High Tidal Volume Ventilation ◽  
Volume Ventilation ◽  
Closed Airway

Independent of airway pressure, pulmonary resistance is known to fall with increasing tidal volumes, traditionally thought to result from radial traction on the airways. R. C. Anafi and T. A. Wilson ( J Appl Physiol 91: 1185–1192, 2001) recently presented a model of a single terminal airway that explains the tidal volume-associated fall in resistance with an additional mechanism pertinent to narrow airways: a stable, nearly closed airway that is challenged with an increase in tidal volume “pops open” to become a stable, well-opened airway, and thus resistance drops suddenly. To test this model in vivo, the effects of high (24 ml/kg) and low (9 ml/kg) tidal volume in bronchoconstricted lungs were assessed using 1) the multiple inert gas elimination technique (MIGET) and 2) a 15-breath multiple breath inert gas washout (MBW) technique in anesthetized pigs. With high tidal volume, ventilation/perfusion (V̇a/Q̇) mismatch was reduced (log SD Q̇ from 1.30 ± 0.11 to 1.09 ± 0.12, P < 0.05), and blood flow to lung units with V̇a/Q̇ ratios < 0.1 was significantly reduced (37 ± 4% of cardiac output to 7 ± 4%, P < 0.05). Dynamic compliance was twice as high during high-tidal-volume ventilation ( P = 0.002). MBW analysis revealed that, while heterogeneity of ventilation during bronchoconstriction was not significantly different between either low or high tidal volume (log SD V̇mbw = 1.39 ± 0.09 and 1.34 ± 0.02, respectively), preinspiratory lung volume (PILV) decreased by 42% with low-tidal-volume ventilation ( P < 0.05), whereas it did not change with high-tidal-volume ventilation. The higher PILV during high tidal volume is also consistent with Anafi and Wilson's model. In summary, the outcomes from MIGET, and to some extent the MBW, in our anesthetized and mechanically ventilated pigs are consistent with a bistable terminal airway model as proposed by Anafi and Wilson. However, our data do not allow exclusion of other mechanisms that may lead to improved ventilatory distribution when tidal volume is increased.

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