PMID- 11213077
OWN - NLM
STAT- MEDLINE
DCOM- 20010308
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 71
IP  - 2
DP  - 2001 Jan 27
TI  - Lung preconditioning with N-acetyl-L-cysteine prevents reperfusion injury after 
      liver no flow-reflow: a dose-response study.
PG  - 300-6
AB  - BACKGROUND: Circulating xanthine oxidase activity and the generated oxidants have 
      been linked to lung reperfusion injury from no flow-reflow conditions in other 
      organs after organ transplantation or surgery. N-acetyl-1-cysteine (NAC), an 
      oxidant scavenger, promotes glutathione in its reduced form (GSH) that is 
      depleted during ischemia. We have recently demonstrated its efficacy in 
      protecting lungs from reperfusion injury if administered during reperfusion of 
      postischemic liver. We now investigated whether preconditioning of lungs with NAC 
      could attenuate lung respiratory or vascular derangement after no flow-reflow 
      (ischemia-reperfusion, IR) and if this depends on lung GSH levels. METHODS: Rat 
      isolated livers were stabilized and perfused with modified Krebs-Henseleit 
      solution (KH) (control, n=12) or made ischemic (no flow, IR-0, n=12) for 2 hr. 
      Meanwhile, lungs were isolated, ventilated, and stabilized (KH+bovine albumin 
      5%). Serial perfusion (15 min) of liver+lung pairs took place followed by lung 
      only recirculation (45 min) with the accumulated solution. Another three controls 
      and three ischemic groups included lungs treated during stabilization with NAC at 
      100 mg x kg(-1), 150 or 225 mg x kg(-1) (in 2.5, 3.7 or 5.5 mmol solutions, 
      respectively). Results. Ischemic liver damage, expressed by circulating 
      hepatocellular constituents, was associated with pulmonary artery and ventilatory 
      pressure increases by 70-100% of baseline, abnormal wet-to-dry weight ratio, and 
      abnormal bronchoalveolar lavage volume and content in the IR-0 (nontreated) and 
      the IR-100 and IR-225 pretreated lungs. NAC-150 pretreatment afforded 
      preservation for most parameters. GSH content in the IR-150 lung tissue was only 
      11% higher than that of IR-225, but 2-fold that in IR-0 and IR-100 GSH lungs. 
      CONCLUSION: Lung preconditioning with NAC prevents reperfusion injury but not in 
      a dose-related manner. Although enhanced GSH tissue content explains lung 
      protection, GSH-independent NAC activity is another possibility.
FAU - Weinbroum, A A
AU  - Weinbroum AA
AD  - Department of Anesthesiology, Tel Aviv Sourasky Medical Center, Israel. 
      draviw@tasmc.health.gov.il
FAU - Kluger, Y
AU  - Kluger Y
FAU - Ben Abraham, R
AU  - Ben Abraham R
FAU - Shapira, I
AU  - Shapira I
FAU - Karchevski, E
AU  - Karchevski E
FAU - Rudick, V
AU  - Rudick V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - GAN16C9B8O (Glutathione)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology/*therapeutic use
MH  - Animals
MH  - Glutathione/analysis
MH  - Liver/*blood supply/enzymology
MH  - *Lung/blood supply/chemistry
MH  - *Lung Transplantation
MH  - Rats
MH  - Regional Blood Flow/physiology
MH  - Reperfusion Injury/*prevention & control
MH  - Time Factors
MH  - Transplantation Conditioning
EDAT- 2001/02/24 12:00
MHDA- 2001/03/10 10:01
CRDT- 2001/02/24 12:00
PHST- 2001/02/24 12:00 [pubmed]
PHST- 2001/03/10 10:01 [medline]
PHST- 2001/02/24 12:00 [entrez]
AID - 10.1097/00007890-200101270-00023 [doi]
PST - ppublish
SO  - Transplantation. 2001 Jan 27;71(2):300-6. doi: 10.1097/00007890-200101270-00023.