Publication

Attenuation of pancreatitis-induced pulmonary injury by aerosolized hypertonic saline.

Shields, C J
; 
Sookhai, S
; 
Winter, D C
; 
Dowdall, J F
; 
Kingston, G
; 
Parfrey, N
; 
Wang, J H
; 
Kirwan, W O
; 
Redmond, H P
Author
Shields, C J
 Sookhai, S
 Winter, D C
 Dowdall, J F
 Kingston, G
 Parfrey, N
 Wang, J H
 Kirwan, W O
 Redmond, H P
Advisors
Editors
Other Contributors
Departments
Department of Academic Surgery, Cork University Hospital, Wilton, Cork.
Date
2012-02-03T15:09:48Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Acute Disease
Adjuvants, Immunologic/*administration & dosage/therapeutic use
Administration, Inhalation
Animals
Apoptosis/physiology
Bronchoalveolar Lavage Fluid/chemistry
Chemotaxis, Leukocyte/physiology
Endothelial Growth Factors/secretion
Humans
Intercellular Signaling Peptides and Proteins/secretion
Lung/chemistry/metabolism
Lung Diseases/*drug therapy/*etiology/physiopathology
Lymphokines/secretion
Male
Models, Animal
Neutrophils/physiology
Organ Size/drug effects
Pancreatitis/chemically induced/*complications
Peroxidase/analysis
Proteins/analysis
Rats
Rats, Sprague-Dawley
Saline Solution, Hypertonic/*administration & dosage/therapeutic use
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
URI
https://hdl.handle.net/10147/209009
Abstract
BACKGROUND: The immunomodulatory effects of hypertonic saline (HTS) provide potential strategies to attenuate inappropriate inflammatory reactions. This study tested the hypothesis that administration of intratracheal aerosolized HTS modulates the development of lung injury in pancreatitis. METHODS: Pancreatitis was induced in 24 male Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). At 24 and 48 h, intratracheal aerosolized HTS (7.5% NaCl, 0.5 mL) was administered to 8 rats, while a further 8 received 0.5 mL of aerosolized normal saline (NS). At 72 hours, pulmonary neutrophil infiltration (myeloperoxidase activity) and endothelial permeability (bronchoalveolar lavage and wet:dry weight ratios) were assessed. In addition, histological assessment of representative lung tissue was performed by a blinded assessor. In a separate experiment, polymorphonucleocytes (PMN) were isolated from human donors, and exposed to increments of HTS. Neutrophil transmigration across an endothelial cell layer, VEGF release, and apoptosis at 1, 6, 12, 18, and 24 h were assessed. RESULTS: Histopathological lung injury scores were significantly reduced in the HTS group (4.78 +/- 1.43 vs. 8.64 +/- 0.86); p < 0.001). Pulmonary neutrophil sequestration (1.40 +/- 0.2) and increased endothelial permeability (6.77 +/- 1.14) were evident in the animals resuscitated with normal saline when compared with HTS (0.70 +/- 0.1 and 3.57 +/- 1.32), respectively; p < 0.04). HTS significantly reduced PMN transmigration (by 97.1, p = 0.002, and induced PMN apoptosis (p < 0.03). HTS did not impact significantly upon neutrophil VEGF release (p > 0.05). CONCLUSIONS: Intratracheal aerosolized HTS attenuates the neutrophil-mediated pulmonary insult subsequent to pancreatitis. This may represent a novel therapeutic strategy.
Language
eng
Citation
Surg Infect (Larchmt). 2001 Fall;2(3):215-23; discussion 223-4.
ISSN
1096-2964 (Print)
1096-2964 (Linking)
eISSN
ISBN
DOI
10.1089/109629601317202696
PMID
12593711
PMCID
Sponsorships
Funding Sources
Funding Amounts
Grant Identifiers
Methodology
Duration
Ethical Approval