Nitric Oxide Ventilation of Rat Lungs from Non-Heart-Beating Donors Improves Posttransplant Function

https://doi.org/10.1111/j.1600-6143.2009.02840.xGet rights and content
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Lungs from non-heart-beating donors (NHBDs) would enhance the donor pool. Ex vivo perfusion and ventilation of NHBD lungs allows functional assessment and treatment. Ventilation of rat NHBD lungs with nitric oxide (NO) during ischemia, ex vivo perfusion and after transplant reduced ischemia-reperfusion injury (IRI) and improved lung function posttransplant. One hour after death, Sprague-Dawley rats were ventilated for another hour with either 60% O2 or 60% O2/40 ppm NO. Lungs were then flushed with 20-mL cold Perfadex, stored cold for 1 h, perfused in an ex vivo circuit with Steen solution and warmed to 37°C, ventilated 15 min, perfusion-cooled to 20°C, then flushed with cold Perfadex and stored cold. The left lung was transplanted and ventilated separately. Recipients were sacrificed after 1 h. NO-ventilation was associated with significantly reduced wet:dry weight ratio in the ex vivo circuit, better oxygenation, reduced pulmonary vascular resistance, increased lung tissue levels of cGMP, maintained endothelial NOS eNOS, and reduced increases in tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS). NO-ventilation had no effect on MAP kinases or NF-κB activation. NO administration to NHBDs before and after lung retrieval may improve function of lungs from NHBDs.

Key words

Actin cytoskeleton
assessment
ex vivo assessment
experimental transplantation
graft function
ischemia/reperfusion injury
lung transplantation
MAP kinase
nitric oxide
non-heart-beating donors
nuclear factor-kappa B (NF-κB)
pulmonary vascular physiology
rat
TNF-alpha

Abbreviations:

cGMP
cyclic guanosine monophosphate
ERK
extracellular signal-regulated kinases
HMVECs
human pulmonary microvascular endothelial cells
HUVECs
human umbilical vein endothelial cells
IRI
ischemia-reperfusion injury
LTX
lung transplantation
MAPK
mitogen-activated protein kinase
NHBD
non-heart-beating donor
NF-κB
nuclear kappa factor B
NO
nitric oxide
NOS
nitric oxide synthase
eNOS
endothelial NOS
iNOS
inducible NOS
nNOS
neuronal NOS
p38
p38-MAPK
PA
pulmonary artery
PVR
pulmonary vascular resistance
SAPK/JNKs
stress-activated/c-Jun NH2-terminal kinases
TNF-α
tumor necrosis factor alpha

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