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 phosphodiesterases 4 and 1, KF19514, is useful in the treatment of systemic anaphylaxis in fentanyl-anesthetized rabbits. Eighty-two rabbits were randomly allocated to 7 groups. Groups I-1 (0.01 mg x kg(-1)), I-2 (0.1 mg x kg(-1)), and I-3 (1 mg x kg(-1)) received KF19514 10 minutes before antigen challenge, with Group II serving as control. Group IV and Group V received KF19514 and aminophylline 1 minutes after antigen challenge, respectively, with Group 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 pulmonary compliance (C(dyn)) was significantly higher in Group I-3 than in Group 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 comparable, but central venous pressure in Group IV was significantly lower than in Group V. In conclusion, the administration of KF19514, an inhibitor of PDEs 4 and 1, to rabbits either before or after antigen challenge improved bronchoconstriction provoked by systemic anaphylaxis with minimal concomitant cardiovascular side effects compared with aminophylline, suggesting that this agent may be useful in the treatment of systemic anaphylaxis.
Hasome
N
N
Department of Anesthesiology, Jichi Medical School, Minamikawachi, Tochigi, Japan.
Mitsuhata
H
H
Saitoh
J
J
Takeuchi
H
H
Shimizu
R
R
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000707:Anaphylaxis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006439:Hemodynamics / Q000187:drug effects; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008170:Lung Compliance / Q000187:drug effects; D009287:Naphthyridines / Q000627:therapeutic use*; D043264:Phosphodiesterase I; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011817:Rabbits
D001993:Bronchodilator Agents; D007527:Isoenzymes; C106878:KF 19514; D009287:Naphthyridines; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D043264:Phosphodiesterase I; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4