Bovine surfactant (surfactant TA) therapy in immature baboons with hyaline membrane disease

Abstract

As a prelude to clinical trials with a bovine surfactant (surfactant TA), in human infants with hyaline membrane disease, pulmonary and hemodynamic changes following its instillation in premature baboons were investigated. Baboons, delivered by cesarean section at 141 +/- 3.5 days (mean +/- SD, 77% gestation), were provided with intensive care. At 2 hours of age in one group (n = 10), 100 mg/kg of surfactant TA (reconstituted bovine surfactant, Tokyo Tanabe Co., Tokyo) was instilled into the lungs. Sequential measurements and monitoring of pulmonary and hemodynamic variables were carried out in these ten baboons and in a control group of five baboons for 16 hours, at which time the experiments were electively terminated. At birth, the pulmonary compliance, findings of chest radiographs, ratio of arterial PO2 to alveolar PO2, and respirator variables needed to maintain normal blood gas and acid base status were identical in both groups and indicative of severe hyaline membrane disease. Following surfactant instillation, the treated group demonstrated a rapid increase in PO2 with significantly improved ratio of arterial PO2 to alveolar PO2 (from a mean +/- SD pretreatment value of 0.21 +/- 0.11 to 0.45 +/- 0.11 by 16 hours). Pulmonary compliance improved similarly (from pretreatment value of 0.18 +/- 0.06 mL/cm H2O/kg to 0.27 +/- 0.09 mL/cm H2O/kg). Significant reduction in respirator support variables could be achieved in all treated animals; however, in the control animals, the pulmonary status worsened as evidenced by increasing mean airway pressure and respirator variables to keep normal blood gas and acid base status, thus worsening compliance. At autopsy, pulmonary pressure-volume curves were significantly different with large hysteresis obtained in the surfactant-treated group. Although no deleterious effect on hemodynamics was noted in surfactant TA-treated animals, a large patent ductus arteriosus was demonstrated by aortography. Increased lung blood flow, probably due to a large patent ductus arteriosus flow, was demonstrated by radiolabeled microsphere technique. The physiologic significance and clinical relevance of these findings in premature baboons treated with surfactant TA are discussed.