Long-term partial liquid ventilation (PLV) with perflubron in the near-term baboon neonate.

PURPOSE: The feasibility and safety of continuous long-term (4-5 day) partial liquid ventilation (PLV) using perflubron was demonstrated in newborn baboons. PLV, a potential therapy for adult and neonatal respiratory distress syndrome (RDS), is conventional mechanical ventilation (CMV) with the lung filled to about functional residual capacity with perfluorochemical liquid. PROTOCOL: As a pilot trial for a larger preclinical study focused on the safety of extended duration PLV, three near term baboons were studied. The animals were delivered by cesarean section, anesthetized, intubated and placed on CMV. The animals were given intratracheal perflubron (30 ml/kg) and maintained on PLV for 96 hours. The transition back to gas ventilation occurred, after draining, over the fifth day (hrs 96-120). RESULTS: Two of the animals were born with normal pulmonary function, while the third developed respiratory distress prior to PLV. All the animals were adequately supported with PLV using moderate ventilator settings and low concentrations of oxygen. Perflubron distribution was enhanced by periodic rotation of the animals. Preliminary histology show vacuolated alveolar macrophages and no evidence of edema or other significant changes in the lungs. Pulmonary function in the RDS animal, after PLV treatment, showed normal gas exchange and lung mechanics. CONCLUSIONS: Three near term baboons, one with clinical RDS, tolerated 4 days of PLV followed by 1 day of CMV without complications using practical clinical management methods.

Toxic effects associated with the administration of deferoxamine in the premature baboon with hyaline membrane disease.

We hypothesized that administration of the iron chelator deferoxamine would inhibit iron-catalyzed free radical generation and lessen the severity of oxygen-induced pulmonary injury. To evaluate its efficacy and safety in premature infants, we administered deferoxamine by intravenous infusion to five premature baboons with hyaline membrane disease supported with conventional ventilation and 100% oxygen for 6 days. Seven animals served as controls. Deferoxamine treatment was initiated at 10 mg/kg per hour but, after the precipitous death of the first animal, was progressively reduced to 1.25 mg/kg per hour in the other animals. Four of five deferoxamine-treated baboons developed cardiovascular collapse and all five died by 42 hours. Five of the seven control animals survived the 6-day experimental period. Since cardiovascular toxic effects have not previously been reported, these findings suggest unique vulnerability of the immature cardiovascular system to iron chelation.