Comparison of the anti-anaphylactic effects of milrinone, sulmazole and theophylline in the rat.
Milrinone and sulmazole, two recently developed cardiotonic drugs, inhibit specific fractions of the phosphodiesterase (PDE) isozyme system, while theophylline inhibits the PDE complex aspecifically. Since these drugs were shown to have anti-allergic effects in isolated lungs, we wanted to study milrinone and sulmazole in comparison with theophylline in an in vivo model of anaphylaxis. For this purpose, actively sensitized rats were intravenously challenged with antigen, while tracheal pressure, oesophageal pressure, blood pressure and airflow were continuously monitored. Antigen challenge induced a transient bronchoconstriction and a persistent fall in blood pressure until death occurred. Anaphylactic shock was consistently followed by metabolic acidosis. Milrinone, 3 mg/kg, and theophylline, 40 mg/kg (but not 10 mg/kg), reduced anaphylactic bronchoconstriction. Sulmazole, 40 mg/kg, almost abolished bronchoconstriction. Although milrinone, sulmazole and theophylline, 40 mg/kg, caused a fall in blood pressure prior to antigen challenge, total fall in blood pressure (drug-induced and antigen-induced) was not affected by these drugs. Surprisingly, sulmazole reduced mortality significantly. This phenomenon is probably related to the less severe metabolic acidosis in the presence of sulmazole.
Post
M J
MJ
Department of Pharmacotherapy, Faculty of Pharmacy, University of Utrecht, The Netherlands.
te Biesebeek
J D
JD
Wemer
J
J
van Rooij
H H
HH
Porsius
A J
AJ
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000403:Airway Resistance / Q000187:drug effects; D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D007093:Imidazoles / Q000494:pharmacology*; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D020105:Milrinone; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D013806:Theophylline; C029758:sulmazole; D020105:Milrinone