COMBINED SURFACTANT THERAPY AND INHALED NITRIC-OXIDE IN RABBITS WITH OLEIC ACID-INDUCED ACUTE RESPIRATORY-DISTRESS SYNDROME

Intratracheal administration of surfactant and inhaled nitric oxide (I NO) have had variable effects in clinical trials on patients with acut e respiratory distress syndrome (ARDS). We hypothesized that combined treatment with exogenous surfactant and INO may have effects in experi mental ARDS. After intravenous infusion of oleic acid in adult rabbits and 4-6 h of ventilation, there was more thana 40% reduction in both dynamic compliance (Cdyn) of the respiratory system and functional res idual capacity (FRC), a 50% increment of respiratory resistance (Rrs), a 70% reduction in Pa-O2/FIO2 and an increase in intrapulmonary shunt ing ((Q) over dot s/(Q) over dot T) from 4.4 to 33.5%. The animals wer e then allocated to groups receiving (1) neither surfactant nor INO (c ontrol), (2) 100 mg/kg of surfactant (5) administered intratracheally, (3) 20 ppm INO (NO), or (4) 100 mg/kg of surfactant and 20 ppm INO (S NO), and subsequently ventilated for 6 h. After the period of ventilat ion, the animal lungs were used for analysis of disaturated phosphatid ylcholine (DSPC) and total proteins (TP) in bronchoalveolar lavage flu id (BALF), and for determination of alveolar volume density (Vv). The animals in the control group had the lowest survival rate, and no impr ovement in lung mechanics and blood oxygenation, whereas those In the S group had a modest but statistically significant improvement in Cdyn , Rrs, Pa-O2 and FRC, reduced (Q) over dot s/(Q) over dot T, lowered m inimum surface tension (gamma(min)) of BALF, and increased DSPC/TP and alveolar Vv. The NO group had increased Pa-O2 and reduced (Q) over do ts/(Q) over dot T. The SNO group showed improved Cdyn, Rrs, FRC, DSPC/ TP, alveolar Vv, and gamma(min) of PALE comparable to the S group, but there was a further increase in survival rate and Pa-O2, and addition al reduction in (Q) over dot s/(Q) over dot T and TP in BALF. These re sults indicate that, in this animal model of ARDS, a combination of su rfactant therapy and INO is more effective than either treatment alone .