EFFICACY OF SYNTHETIC PEPTIDE-CONTAINING SURFACTANT IN THE TREATMENT OF RESPIRATORY-DISTRESS SYNDROME IN PRETERM INFANT RHESUS-MONKEYS

Studies were conducted to assess the efficacy and safety of a syntheti c peptide-containing surfactant in the treatment of respiratory distre ss syndrome (RDS) in preterm (approximately 80% of normal gestation) i nfant rhesus monkeys. Surfactant was prepared consisting of the phosph olipids dipalmitoylphosphatidyl choline and palmitoyl-oleoyl phosphati dyl glycerol and a synthetic peptide modeled after surfactant protein B (SP-B), ''KL(4)-Surfactant'' contained a peptide having the sequence KLLLLKLLLLKLLLLKLLLLK, where ''K'' is lysine and ''L'' is leucine. Th e peptide was selected because it mimics the repeating stretches of hy drophobic residues with intermittent basic hydrophilic residues seen i n SP-B. KL(4)-Surfactant was shown to have biophysical activity assess ed as the ability to lower surface tension at an air-liquid interface in a pulsating bubble surfactometer. Thirty premature rhesus monkeys w ere treated shortly after birth with one dose of KL(4)-Surfactant. The arterial to alveolar oxygen partial pressure ratio (a/A) was found to rise from a pretreatment level of 0.11 +/- 0.01 (mean +/- SEM). indic ative of severe RDS, to 0.40 +/- 0.02 at 12-13 h post-treatment. The i mprovement in oxygenation persisted throughout the study period, with a mean a/A at 22-23 h of 0.45 +/- 0.07. Chest radiographs and gross an d microscopic examination of the lungs all confirmed the reversal of t he atelectasis seen before treatment. Animals treated with a dose of 2 00 mg/kg showed a faster, more consistent, and greater response than d id a group treated with an average dose of 127 mg/kg. There was no evi dence of toxicity after treatment with the higher dose as demonstrated by physiologic, hematologic, biochemical, and pathologic data. The im portance of the peptide in the synthetic surfactant was apparent from the results obtained with a control group of nine premature monkeys tr eated with a non-peptide-containing surfactant; the a/A of this group was 0.15 +/- 0.03 at nine hours of age as compared with a value of 0.3 8 +/- 0.02 for 30 comparable animals receiving KL(4)-Surfactant.