title: Heliox attenuates lung inflammation and structural alterations in acute lung injury.
abstract: Low-density gas mixtures, such as heliox, were shown to reduce the work of breathing and facilitate the distribution of inspired gas. Since supplemental ventilatory and oxygen requirements may lead to pulmonary inflammation and structural alterations, we hypothesized that by reducing these requirements, heliox breathing may attenuate the acute inflammatory and structural changes associated with acute lung injury. Spontaneously breathing neonatal pigs were anesthetized, instrumented, supported with continuous positive airway pressure (CPAP), injured with oleic acid, and randomized to nitrox (n = 6) or heliox (n = 5).F(I)O(2) was titrated for pulse oximetry (SpO(2)) 95 +/- 2% for 4 hr. Gas exchange and pulmonary mechanics were measured. Lungs were analyzed for myeloperoxidase (MPO), interleukin-8 (IL-8), and histomorphometery. Relationships between physiologic indices and cumulative lung structure and inflammatory indices were evaluated. With heliox, compliance was significantly greater, while tidal volume, frequency, minute ventilation, F(I)O(2), arterial carbon dioxide tension (PaCO(2)), MPO, and IL-8 were significantly lower compared to nitrox. The expansion index and number of exchange units were significantly greater with heliox, while the exchange unit area (EUA) was smaller. MPO was significantly and positively correlated with F(I)O(2) (r = 0.76) and EUA (r = 0.63), and negatively correlated with number of open exchange units/field (r = -0.73). Compared to breathing nitrox, these data indicate that heliox improved the distribution of inspired gas, thereby recruiting more gas exchange units, improving gas exchange efficiency, reducing ventilatory and oxygen requirements, and attenuating lung inflammation. These data suggest that heliox breathing may have the combined therapeutic benefits of attenuating lung inflammation by reducing mechanical and oxidative stress in the clinical management of acute lung injury.
authors.affiliation: Division of Neonatology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
authors.forename: Ursula S
authors.initials: US
authors.lastname: Nawab
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Touch
authors.forename: Tami
authors.initials: T
authors.lastname: Irwin-Sherman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Blackson
authors.forename: Jay S
authors.initials: JS
authors.lastname: Greenspan
authors.forename: Guangfa
authors.initials: G
authors.lastname: Zhu
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Shaffer
authors.forename: Marla R
authors.initials: MR
authors.lastname: Wolfson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D045422:Continuous Positive Airway Pressure; D004195:Disease Models, Animal; D006371:Helium / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D009584:Nitrogen / Q000494:pharmacology; D010092:Oximetry; D010100:Oxygen / Q000097:blood / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D012129:Respiratory Function Tests; D015656:Respiratory Mechanics; D013552:Swine
chemical_list: D016209:Interleukin-8; D006371:Helium; C041364:nitrox; C038949:heliox; D009195:Peroxidase; D009584:Nitrogen; D010100:Oxygen