An isoenzyme-selective inhibitor of phosphodiesterase 4 and 1, KF19514, may be useful in the treatment of systemic anaphylaxis: An in vivo study in rabbits

The present study was conducted to determine whether an inhibitor of phosph odiesterases 4 and 1, KF19514, is useful in the treatment of systemic anaph ylaxis in fentanyl-anesthetized rabbits. Eighty-two rabbits were randomly a llocated to 7 groups. Groups I-1 (0.01 mg . kg(-1)), I-2 (0.1 mg . kg(-1)), and I-3 (1 mg kg(-1)) received KF19514 10 minutes before antigen challenge , with Group It serving as control. Group TV and Group V received KF19514 a nd aminophylline I minutes after antigen challenge, respectively, with Grou p III serving as control. The survival rate was higher in Groups I than in Group II, rates were similar in Groups I-1, I-2, and I-3. The survival rate was also higher in Group IV than in Group III. Pulmonary resistance (R-L) was significantly lower in Groups I-2 and I-3 than in Group II. Dynamic pul monary compliance (C-dyn) was significantly higher in Group I-3 than in Gro up II. Heart rate and central venous pressure were similar in Groups I and II. In Groups III, IV, and V, heart rate and mean arterial pressure were co mparable, but central venous pressure in Group IV was significantly lower t han in Group V. In conclusion, the administration of KF19514, an inhibitor of PDEs 4 and 1, to rabbits either before or after antigen challenge improv ed bronchoconstriction provoked by systemic anaphylaxis with minimal concom itant cardiovascular side effects compared with aminophylline, suggesting t hat this agent may be useful in the treatment of systemic anaphylaxis.