Effects of diethylcarbamazine and cromolyn sodium on hypoxic pulmonary vasoconstriction in dogs.
Evidence has recently been accumulated that leukotrienes might be involved in the still unknown biochemical mechanism of hypoxic pulmonary vasoconstriction. We therefore investigated the effects of i.v. cromolyn sodium, which prevents the release of leukotrienes from mast cells by a membrane stabilizing effect, and of i.v. diethylcarbamazine citrate (DEC), a leukotriene synthesis inhibitor, in 13 dogs challenged with the inhalation of 10% O2 in nitrogen (FIO2 0.1) during 10 min. The dogs were anaesthetized with pentobarbital, paralysed with pancuronium, ventilated with a FIO2 of 0.4 and equipped with catheters for the purpose of pulmonary and systemic vascular pressure measurements and thermodilution cardiac output determinations. Thirty minute infusions of DEC at respectively 100 mg, 400 mg, 2 g, 5 g, 10 g and 15 g (one dosage per dog) did not alter the hypoxic pulmonary pressor response. Dosages of 10 g and 15 g DEC were associated with systemic hypotension, and one additional dog given 20 g died in refractory shock. A continuous infusion of cromolyn sodium inhibited hypoxic pulmonary vasoconstriction, partially at 3 and 4.5 mg X kg-1 X min-1 (2 dogs) and completely at 6 mg X kg-1 X min-1 (3 dogs). A lower dosage of 1 mg X kg-1 X min-1 cromolyn sodium (one dog) had no circulatory effect. These results do not support the hypothesis that hypoxic pulmonary vasoconstriction is mediated by vasoconstricting leukotrienes in the dog. The mechanisms accounting for the inhibition of the pulmonary hypoxic pressor response by cromolyn sodium are uncertain.
Naeije
R
R
Leeman
M
M
Lejeune
P
P
D000818:Animals; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000494:pharmacology*; D004049:Diethylcarbamazine / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D000860:Hypoxia / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D013189:SRS-A / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D013189:SRS-A; D004205:Cromolyn Sodium; D004049:Diethylcarbamazine