Document Detail

Administration of poly(ADP-ribose) polymerase inhibitor into bronchial artery attenuates pulmonary pathophysiology after smoke inhalation and burn in an ovine model.
MedLine Citation:
PMID:  22995423     Owner:  NLM     Status:  MEDLINE    
Poly(ADP-ribose) polymerase (PARP) is well known to be an enzyme that repairs damaged DNA and also induces cell death when overactivated. It has been reported that PARP plays a significant role in burn and smoke inhalation injury, and the pathophysiology is thought to be localized in the airway during early stages of activation. Therefore, we hypothesized that local inhibition of PARP in the airway by direct delivery of low dose PJ-34 [poly(ADP-ribose) polymerase inhibitor] into the bronchial artery would attenuate burn and smoke-induced acute lung injury. The bronchial artery in sheep was cannulated in preparation for surgery. After a 5-7 day recovery period, sheep were administered a burn and inhalation injury. Adult female sheep (n=19) were divided into four groups following the injury: (1) PJ-34 group A: 1h post-injury, PJ-34 (0.003mg/kg/h, 2mL/h) was continuously injected into the bronchial artery, n=5; (2) PJ-34 group B: 1h post-injury, PJ-34 (0.03mg/kg/h, 2mL/h) was continuously injected into bronchial artery, n=4; (3) CONTROL GROUP: 1h post-injury, an equivalent amount of saline was injected into the bronchial artery, n=5; (4) Sham group: no injury, no treatment, same operation and anesthesia, n=5. After injury, all animals were placed on a ventilator and fluid resuscitated equally. Pulmonary function as evaluated by measurement of blood gas analysis, pulmonary mechanics, and pulmonary transvascular fluid flux was severely deteriorated in the control group. However, the above changes were markedly attenuated by PJ-34 infusion into the bronchial artery (P/F ratio at 24h: PJ-34 group A 398±40*, PJ-34 group B 438±41*†‡, Control 365±58*, Sham 547±47; * vs. sham [p<0.05], † vs. control [p<0.05], ‡ vs. PJ-34 group A [p<0.05]). Our data strongly suggest that local airway production of poly(ADP-ribose) polymerase contributes to pulmonary dysfunction following smoke inhalation and burn.
Atsumori Hamahata; Perenlei Enkhbaatar; Matthias Lange; Takashi Yamaki; Hiroyuki Sakurai; Katsumi Shimoda; Hiroaki Nakazawa; Lillian D Traber; Daniel L Traber
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-17
Journal Detail:
Title:  Burns : journal of the International Society for Burn Injuries     Volume:  38     ISSN:  1879-1409     ISO Abbreviation:  Burns     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-05     Completed Date:  2013-04-18     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  8913178     Medline TA:  Burns     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1210-5     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.
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MeSH Terms
Acute Lung Injury / drug therapy,  physiopathology
Bronchial Arteries / drug effects
Burns / drug therapy*
Disease Models, Animal
Enzyme Inhibitors / pharmacology*,  therapeutic use
Lung / drug effects*
Phenanthrenes / pharmacology*
Poly(ADP-ribose) Polymerases / antagonists & inhibitors*
Respiratory Function Tests
Smoke Inhalation Injury / drug therapy*,  physiopathology
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; 0/Phenanthrenes; EC Polymerases

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