Liquid Ventilation in the Respiratory Distress Syndrome

Abstract

S ince 1958 a number of investigators have reported on the use of liauid ventilation in various animal models.' Most of these studies have been canied out on small adult animals, such as mice, in an experimental system in which the animal is immersed in fluorocarbon. The difficulties encountered with this system have centered around three problems: ( 1 ) lack of normothermia; ( 2 ) lack of adequate gas exchange, resulting in the accumulation of CO,; and (3 ) depressed tissue metabolism., Because of these d%culties, one of us3 developed a system to artificially vendate animals, using fluorocarbon, which operates on the principal of the iron lung. The experiments deal with a specific problem: the atelectatic lung of the immature newborn mini-pig and the application of liquid ventilation to support breathing mechanics. These studies concern two questions: ( 1 ) Does fluorocarbon ventilation alter lung lipid metabolism? ( 2 ) Is there a difference in the ability of the immature fetal lung to synthesize surfactant compared to that of the mature fetal lung? The animals used were fetal mini-pigs of 95, 100 and 110 days gestation, 112 days being the normal gestational period. Fetus weight at the three periods was 322 51 gm ( N = 28), 344 * 48 gm ( N = 20) and 470 + 75 gm ( N = 32); lung fat free dry weight increased from 687 * 145 mg to 739 * 173 mg to 773 196 mg. The phospholipid content of the lung tissue almost doubled from day 100 (83 * 16 mg) to day 110 ( 137 + 32 mg) . Electronmicroscopy shows a marked increase in lamellar bodies within the type 2 cells over the period studied. After delivery by caesarean section the trachea and carotid artery were cannulated, and the fetus was immediately placed on liquid or gaseous 0, ventilation. Figure 1 shows an example of Po,, Pco, and blood pressure values for a 95-day-old fetus. The Po, shown is high, most values being about 95 mm Hg. Similar data were obtained for all animals subjected to liquid ventilation regardless of age. Gaseous 0, ventilation at 95 days was nearly impossible, with 75 percent of the animals dying within 15 minutes. At 100 days it was possible to maintain animals for about 90 minutes but with great difficulty. Animals of 110 days' gestation could be maintained without difficulty and Po,, Pco, and blood pressure values were similar to those shown in Figure 1. To determine the effect of liquid vs gaseous 0, ventilation on lung tissue metabolism, acetate-U-14C and choline-methyl- were injected via the carotid artery. Acetate was used to determine fatty acid synthesis and subsequent fatty acid incorporation into lecithin, and ~hol ine-~H to determine lecithin synthesis. Experiments were terminated 45, 90 and 180 minutes after isotope injection. Regardless of age or method of ventilation 45 minutes after isotope administration, 60 percent of the acetate incorporated into lung lipid was found in lecithin, while only 25 percent of the acetate incorporated into liver lipids was found in lecithin. No signs-