Glycine ameliorates lung reperfusion injury after cold preservation in an ex vivo rat lung model

AbstractTransfusion-related acute lung injury (TRALI) is a hazardous complication of transfusion and has become the leading cause of transfusion-related death in the United States and United Kingdom. Although leukoagglutinating antibodies have been frequently shown to be associated with the syndrome, the mechanism by which they induce TRALI is poorly understood. Therefore, we reproduced TRALI in an ex vivo rat lung model. Our data demonstrate that TRALI induction by antileukocyte antibodies is dependent on the density of the cognate antigen but does not necessarily require leukoagglutinating properties of the antibody or the presence of complement proteins. Rather, antibody-mediated activation of neutrophils seems to initiate TRALI, a process that could be triggered by neutrophil stimulation with fMLP. Antibody-mediated neutrophil activation and subsequent release of reactive oxygen species may thus represent key events in the pathophysiologic cascade that leads to immune TRALI.

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Preparation of In-Vivo Rat Lung Model for Ischemia-Reperfusion Injury

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-2007-1013877 ◽

1993 ◽

Vol 41 (05) ◽

pp. 304-307 ◽

Cited By ~ 3

Author(s):

N. Ohno ◽

H. Yokomise ◽

T. Fukuse ◽

T. Hirata ◽

S. Hitomi ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Lung Model ◽

Rat Lung

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Keratinocyte growth factor attenuates hydrostatic pulmonary edema in an isolated, perfused rat lung model

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.3.h1311 ◽

2001 ◽

Vol 280 (3) ◽

pp. H1311-H1317 ◽

Cited By ~ 3

Author(s):

David A. Welsh ◽

Benoit P. H. Guery ◽

Bennett P. Deboisblanc ◽

Elizabeth P. Dobard ◽

Colette Creusy ◽

...

Keyword(s):

Growth Factor ◽

Pulmonary Edema ◽

Ex Vivo ◽

Keratinocyte Growth Factor ◽

Lung Model ◽

Rat Lung ◽

Ex Vivo Model ◽

Lung Weight ◽

Edema Formation ◽

Alveolar Epithelial

Hydrostatic pulmonary edema is a common complication of congestive heart failure, resulting in substantial morbidity and mortality. Keratinocyte growth factor (KGF) is a mitogen for type II alveolar epithelial and microvascular cells. We utilized the isolated perfused rat lung model to produce hydrostatic pulmonary edema by varying the left atrial and pulmonary capillary pressure. Pretreatment with KGF attenuated hydrostatic edema formation. This was demonstrated by lower wet-to-dry lung weight ratios, histological evidence of less alveolar edema formation, and reduced alveolar accumulation of intravascularly administered FITC-labeled large-molecular-weight dextran in rats pretreated with KGF. Thus KGF attenuates injury in this ex vivo model of hydrostatic pulmonary edema via mechanisms that prevent increases in alveolar-capillary permeability.

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The protective effect of prone lung position on ischemia–reperfusion injury and lung function in an ex vivo porcine lung model

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2018.08.101 ◽

2019 ◽

Vol 157 (1) ◽

pp. 425-433 ◽

Cited By ~ 10

Author(s):

Hiromichi Niikawa ◽

Toshihiro Okamoto ◽

Kamal S. Ayyat ◽

Yoshifumi Itoda ◽

Carol F. Farver ◽

...

Keyword(s):

Lung Function ◽

Protective Effect ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ex Vivo ◽

Ischemia Reperfusion ◽

Lung Model

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MCI-186 (edaravone), a free radical scavenger, attenuates ischemia–reperfusion injury and activation of phospholipase A2 in an isolated rat lung model after 18h of cold preservation

European Journal of Cardio-Thoracic Surgery ◽

10.1016/j.ejcts.2005.12.005 ◽

2006 ◽

Vol 29 (3) ◽

pp. 304-311 ◽

Cited By ~ 16

Author(s):

Y REYES ◽

T SHIMOYAMA ◽

H AKAMATSU ◽

M SUNAMORI

Keyword(s):

Free Radical ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Free Radical Scavenger ◽

Lung Model ◽

Radical Scavenger ◽

Rat Lung ◽

Cold Preservation ◽

Isolated Rat Lung ◽

Isolated Rat

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Drug Absorption Parameters Obtained Using the Isolated Perfused Rat Lung Model Are Predictive of Rat In Vivo Lung Absorption

The AAPS Journal ◽

10.1208/s12248-020-00456-x ◽

2020 ◽

Vol 22 (3) ◽

Cited By ~ 4

Author(s):

Johanna Eriksson ◽

Erik Sjögren ◽

Hans Lennernäs ◽

Helena Thörn

Keyword(s):

Drug Development ◽

Drug Absorption ◽

Ex Vivo ◽

Lung Model ◽

Pharmacokinetic Data ◽

Rat Lung ◽

Time Profiles ◽

Input Parameters

AbstractThe ex vivo isolated perfused rat lung (IPL) model has been demonstrated to be a useful tool during drug development for studying pulmonary drug absorption. This study aims to investigate the potential use of IPL data to predict rat in vivo lung absorption. Absorption parameters determined from IPL data (ex vivo input parameters) in combination with intravenously determined pharmacokinetic data were used in a biopharmaceutics model to predict experimental rat in vivo plasma concentration-time profiles and lung amount after inhalation of five different inhalation compounds. The performance of simulations using ex vivo input parameters was compared with simulations using in vitro input parameters, to determine whether and to what extent predictability could be improved by using input parameters determined from the more complex ex vivo model. Simulations using ex vivo input parameters were within twofold average difference (AAFE < 2) from experimental in vivo data for all compounds except one. Furthermore, simulations using ex vivo input parameters performed significantly better than simulations using in vitro input parameters in predicting in vivo lung absorption. It could therefore be advantageous to base predictions of drug performance on IPL data rather than on in vitro data during drug development to increase mechanistic understanding of pulmonary drug absorption and to better understand how different substance properties and formulations might affect in vivo behavior of inhalation compounds.

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