The effects of a prostacyclin analog OP-41483 on pulmonary oxygen toxicity in an isolated heart-lung autoperfusion model

Using an isolated canine heart-lung autoperfusion model, the effect of prostacyclin analog (OP-41483) on pulmonary oxygen toxicity was investigated. Twenty-four mongrel dogs were divided into four groups. Groups 1 and 2 inspired oxygen at concentrations (FiO2) of 0.95 and 0.6, respectively, while groups 3 and 4 received OP-41483 (0.1 micrograms/kg/min) in addition to FiO2 of 0.95 and 0.6. Autoperfusion was performed for five hours, and during the experiments the systolic blood pressure was maintained at 100 mmHg and the cardiac output at 40 ml/kg/min. After five hours of perfusion, PaO2 decreased significantly (P less than 0.01) from 410 +/- 49 mmHg to 237 +/- 38 mmHg in group 1, and also decreased significantly (P less than 0.01) from 368 +/- 44 mmHg to 243 +/- 26 mmHg in group 2. However, no significant changes in PaO2 were observed in groups 3 and 4. The pathological examinations clearly revealed perivascular edema and vascular dilation in groups 1 and 2, whereas no abnormal pathological findings were seen in groups 3 and 4. The above results indicate that OP-41483, when administered at the low dose of 0.1 micrograms/kg/min, induces no circulatory changes and exerts an effective action with respect to the prevention of pulmonary edema.