Full-Tidal Liquid Ventilation with Perfluorocarbon for Prevention of Lung Injury in Newborn Non-Human Primates

Abstract

Hyaline membrane disease (HMD), the most common life-threatening respiratory disorder of newborns, is associated with lung injury manifested by alveolar proteinaceous edema. The cause of the disease is thought to be elevated alveolar surface tension due to surfactant deficiency at birth. Treatment with exogenous surfactant may be unsuccessful due to problems in distribution of the surfactant, or inhibition of the surfactant by alveolar proteinaceous edema. Liquid ventilation with oxygen-saturated perfluorocarbon liquid has been proposed as a method to eliminate alveolar surface tension; little is known about the interfacial tension between perfluorocarbon liquids and the lung lining layer. Premature and term newborn monkeys were treated from birth with a pressure-limited, time-cycled liquid ventilator using oxygenated perfluorocarbon liquids (APF-145 and perflubron). Adequate gas exchange was achieved, and pilot experiments suggest long-term survival without adverse sequelae. Although many questions remain, liquid ventilation is a promising tool for the prevention and treatment of lung injury in newborns.

Liquid-assisted ventilation: An alternative respiratory modality

“…92 TLV systems have evolved over the years, and laboratory investigations of the physiological basis of this alternative form of respiratory support have proceeded. Ventilator designs have included manually controlled flow-assist pneumatic systems, 89,93,94 roller pumps with pneumatic/fluidic/electronic controls, 44,86,95 gravity-driven, 96,97 and modified ECLS circuits 98 to cycle liquid between a reservoir and the lung. Whereas this developmental process 99 has subjected the implementation of this technique to criticism on the basis that liquid ventilators were complicated and cumbersome for clinical use, this evolution has now resulted in simplified instrumentation with relatively more sophisticated interactive control strategies than available in most gas ventilators.…”

Vascular Reactivity of Pulmonary Arteries from Premature Lambs Subjected to Liquid Ventilation

“…In animal models of hyaline membrane disease, TLV compares favorably to conventional mechanical ventilation (CMV) with respect to gas exchange, lung mechanics, lung histology and biochemical markers of lung injury [3,6]. TLV has therefore been suggested as a promising tool for the prevention of lung injury in preterm newborns [4].…”

“…Tidal liquid ventilation (TLV) is a technique of respiratory support during which gaseous functional residual capacity and tidal volume are substituted by a perfluorocarbon liquid [4,5]. In animal models of hyaline membrane disease, TLV compares favorably to conventional mechanical ventilation (CMV) with respect to gas exchange, lung mechanics, lung histology and biochemical markers of lung injury [3,6].…”

Four decades of leading‐edge research in the reproductive and developmental sciences: The Infant Primate Research Laboratory at the University of Washington National Primate Research Center

“…The lung injury response was further investigated, and the change in lung proteoglycans with HMD were described [Juul et al, 1993, Juul et al, 1994]. Finally, liquid ventilation with perfluorocarbons was attempted [Jackson et al, 1994b, Tarczy-Hornoch et al, 1996]. These studies were preclinical, and were complemented by clinical studies in critically ill neonates [Leach et al, 1996, Hoekstra et al, 1991, Ferrara et al, 1991].…”