Mechanical Ventilation Effect on Surfactant Content, Function, and Lung Compliance in the Newborn Rat

Abstract

Studies of ventilator-associated lung injury in adult experimental animal models have documented that high tidal volume (TV) results in lung injury characterized by impaired compliance and dysfunctional surfactant. Yet, there is evidence that, in neonates, ventilation with a higher than physiologic TV leads to improved lung compliance. The purpose of our study was to evaluate how lung compliance and surfactant was altered by high TV ventilation in the neonate. We utilized a new model (mechanically air-ventilated newborn rats, 4 -8 d old), and used 40 or 10 mL/kg TV strategies. Age-matched nonventilated animals served as controls. In all animals, dynamic compliance progressively increased after initiation of mechanical ventilation and was significantly greater than basal values after 60 min (p Ͻ 0.01). Lung lavage total surfactant with both TV strategies (p Ͻ 0.05) and the large aggregate fraction (only in TV ϭ 40 mL/kg; p Ͻ 0.01) were significantly increased by 60 min of mechanical ventilation, compared with control animals. Ventilation with 40 mL/kg TV for 60 min adversely affected the lung surfactant surface-tension lowering properties (p Ͻ 0.01). After 180 min of ventilation with 40 mL/kg TV, the lung total surfactant content and dynamic compliance values were no longer distinct from the nonventilated animals' values. We conclude that, in the newborn rat, mechanical ventilation with a higher than physiologic TV increases alveolar surfactant content and, over time, alters its biophysical properties, thus promoting an initial but transient improvement in lung compliance. A single stretch of alveolar type II cells causes an increase in cytosolic calcium resulting in stimulation of surfactant secretion for up to 30 min post stretch (1). In adult animals, this mechanism is operative after an increase in spontaneous breathing tidal volume (2, 3), but never demonstrated after short-term mechanical ventilation with a higher than physiologic tidal volume.Isolated adult rat lungs mechanically ventilated with a tidal volume four times higher than physiologic (25 mL/kg) for 1 h showed a decrease in lung compliance (4), which was associated with an increased conversion from LA to SA within the alveolar space (5). These latter changes likely accounted for the reduction in compliance, inasmuch as adequate biophysical activity of surfactant is dependent on a functional LA fraction.The concept that high tidal volumes may have adverse effects has been consistently demonstrated in multiple animal models of adult ventilator-associated lung injury (6 -8). This concept has driven a variety of strategies aimed at reducing tidal stretch, including permissive hypercapnia (9 -11), as well as studies designed to limit pressure and volume ventilatory parameters associated with tidal stretch (12-14). Indeed, in

Human Meconium Has a Pulmonary Vascular and Airway Smooth Muscle Relaxant Effect

“…For this reason, no blood gases and pH were obtained in the experimental and control animal. In previously published work, we have demonstrated that in newborn rats these ventilator settings result in normal blood pH at the end of 60 min ventilation (16). Yet, the experimental animals' gas exchange status may have differed from our own published data because of meconium-induced ventilation-perfusion mismatch.…”

“…Newborn animals were mechanically ventilated as previously described (16). Briefly, the animals were sedated with an intraperitoneal injection of a mixture of xylazine and ketamine (8 and 80 mg/kg, respectively).…”

“…A custom made previously described mechanical ventilator was used (16). Meconium (prepared as described above) was mixed in saline at a concentration of 65 mg/mL.…”

High Tidal Volume Ventilation Is Not Deleterious in Infant Rats Exposed to Severe Hemorrhage

“…12 Verbrugge et al 25 found that significant changes in surfactant composition and function occurred after application of high V T on top of ZEEP, and setting an adequate PEEP prevented surfactant dysfunction. Martinez et al 12 using a neonatal rat model pointed at stretch-induced surfactant release to explain improved lung compliance after ventilation with extreme V T of 40 mL/kg and ZEEP.…”

“…9 In terms of lung development and alveolarization 2 week old rats correspond to 1-2 year old human infants. 10,11 Ventilator-associated lung injury (VALI) has been studied in infant rats with healthy lungs 7,8,12 or after lipopolysaccharide exposure 13 using V T ventilation ranging from 25 to 40 mL/kg and 0 cmH 2 O PEEP. However, it is not clear how infant rats respond to high but less extreme lung stretch over a longer period of time when compared to low V T ventilation with high PEEP.…”