Argon and the pathophysiology of pulmonary oxygen toxicity

Abstract

Molecular interaction can be determined from biological experiments. In the case of dynamics at the atmosphere-lung interface the physicochemical and atomic attributes of inhalant gases has significant biological and pathogenetic consequences. Hyaline membrane disease (HMD) is a common and sometimes lethal disorder, especially in premature newborns. Current therapy includes artificial ventilation and increased oxygen in the inspired air, despite evidence the lesions can be induced by oxygen enrichment [Lab.Invest. 21 439, 19691. Bilateral cervical vagotomy (BCV) is a standard method of inducing ventilatory distress which leads to HMD [J Exp.Med. 66:397, 1937; Biol.Neonat. 6:340, 1964; Biol. Neonat. 1 1 :6 I. 19671. The lungs of post-vagotomy newborn rabbits show the lesions of HMD in extent directly proportionate to the percentage of oxygen in polybaric (0.2 - 3.0 Atm.Abs) mixtures with nitrogen. Avery [Pediatrics 32:801, 19631 found that lesions of HMD did not form at very low levels of oxygen (3-4% in nitrogen] in various newborn animals. suggesting that inhalant hypoxia was not a pathogenetic factorper se. The observation of lung injury proportionate to oxygen percentage indicates the physiological axiom of gas effects by their partial pressure is an artefact of sea level gas dynamics. The toxic effect of oxygen can be viewed as nitrogen lack. Some lung injury does occur when only 3 and 7 per cent oxygen in nitrogen is used, suggesting rather a specific oxygen effect. When nitrogen is replaced by hydrogen, helium. neon, argon, or sulfur hexafluoride, the extent of lesions often increases, indicating again a fundamental oxygen-nitrogen interaction. Low level studies with hydrogen and argon are especially instructive with and without BCV: (1) extremely long survival without BCV in oxygen-argon at 3% and 7 %; (2) significant but less enhancement of survival in 3% oxygen-hydrogen; (3) no distinction in survival after BCV for 3% oxygen in nitrogen or hydrogen; (4) a pattern of lesion formation in the alternative gas mixtures which suggests nitrogen has a partially protective effect along with its stochastic competition for a conlmon oxygen-nitrogen receptor or transmembrane port; and (5) generally, the mammalian lung is well adapted by evolution to current atmospheric composition but at the price of more inhaled oxygen than is required for cellular function [Perspect.Biol.Med. 13:80, 19691, allowing for toxic effects. The distinctions amongst these gases in the biologic sense are due to differences in their mass, moiloatomic or diatomic structure: possibly viscosity in air passageway flow, inherent energy state, and at low levcls, in the electron saturation of the outer atomic shell. Unbuffered oxygen enrichment of air for ventilatory support is fundamentally injurious; hydrogen has obvious risks in a clinical setting but argon, which is abundant, non-flammable, and relatively non-toxic, may be the diluent gas of choice for ventilatory support.